Journal of Thoracic Oncology

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Of cial Publication of the International Association for the Study of Lung Cancer www.jto.org Journal of Thoracic Oncology

Volume 16, Number 4S, Supplement, MarchApril 2021 2021 Alex A. Adjei, MD, PhD, FACP, Editor-in-Chief

Abstract Book European Lung Cancer Virtual Congress 2021 (ELCC 2021 Virtual) 25–27 March 2021

Guest Editors: European Lung Cancer Virtual Congress 2021 Scientific Committee

JTHO_SUPPLEMENT_COVER.indd 1 16-09-2016 10:25:13 Official Journal of the International Association for the Study of Lung Cancer (IASLC)

Volume 16, Issue 4S, Supplement, April 2021

Abstract Book of the European Lung Cancer Virtual Congress (ELCC 2021 Virtual) 25–27 March 2021

Publication of this Abstract book is supported by the ELCC 2021 Virtual organisers: the European Society for Medical Oncology and the International Association for the Study of Lung Cancer. EDITOR-IN-CHIEF Alex A. Adjei, MD, PhD, FACP Mayo Clinic Rochester, MN, USA

DEPUTY EDITOR STATISTICAL EDITOR EDITOR EMERITUS Satoshi Ishikura, MD, PhD Sumithra Mandrekar, PhD James R. Jett, MD Nagoya City University Mayo Clinic National Jewish Health Nagoya, Japan Rochester, MN, USA Denver, CO, USA

WEB EDITOR REVIEWS EDITOR Cheryl Ho, MD D. Ross Camidge, MD, PhD British Columbia Cancer Agency University of Colorado Cancer Center Vancouver, British Columbia, Canada Aurora, CO, USA

ASSOCIATE EDITORS, EUROPE

Anne-Marie C. Dingemans, MD, PhD Luis M. Montuenga, PhD Dirk de Ruysscher, MD, PhD Pulmonary Medicine Basic Science/Translational Research Radiation Oncology The Netherlands Spain The Netherlands Rafal Dziadziusko, MD Silvia Novello, MD, PhD Paul Van Schil, MD, PhD Medical Oncology University of Turin Thoracic Surgery Poland Turin, Italy Belgium Wilfried Eberhardt, MD Jean Louis Pujol, MD Gabriella Sozzi, PhD Medical Oncology Chest Medicine/Medical Oncology Basic Science/Translational Research Germany France Italy Keith Kerr, MD, FRCPath Martin Reck, MD, PhD Pathology Medical Oncology UK Germany

PUBLICATION STAFF Mary Todd Managing Editor New York ASSOCIATE EDITORS, THE AMERICAS

Andrea Bezjak, MSc, MDCM, FRCPC Jeremy Erasmus, MD Yu Shyr, PhD Radiation Oncology Radiology Biostatistics/Bioinformatics Canada USA USA Jeffrey Bogart, MD Fred R. Hirsch, MD, PhD William Travis, MD Radiation Oncology Translational Research Pathology USA USA USA Michele Carbone, MD, PhD Sai-Hong Ignatius Ou, MD, PhD Graham Warren, MD, PhD Pathology/Basic and Translational Science Medical Oncology/Translational Science Radiation Oncology USA USA Frank C. Detterbeck, MD Thoracic Surgery Eduardo Richardet, MD Ping Yang, MD, PhD USA Medical Oncology Genetic Epidemiology Argentina USA

ASSOCIATE EDITORS, ASIA/AUSTRALIA/REST OF WORLD

Myung-Ju Ahn, MD Tetsuya Mitsudomi, MD James Chih-Hsin Yang, MD Medical Oncology Thoracic Surgery Medical Oncology South Korea Japan Taiwan Abdul-Rahman Jazieh, MD Keunchil Park, MD, PhD Yashushi Yatabe, MD, PhD Medical Oncology Medical Oncology Pathology/Molecular Diagnostics Saudi Ariabia South Korea Japan Thomas John, MD, PhD Emily Stone, M.B.B.S., PhD, FRACP Wen-Zhao Zhong, MD, PhD Medical Oncology/Translational Research Pulmonary Medicine Thoracic Surgery/Translational Oncology Australia Australia China Young Tae Kim, MD, PhD Daniel S.W. Tan, BSc, M.B.B.S., MRCP Thoracic Surgery Medical Oncology South Korea Singapore Shun Lu, MD, PhD Shinichi Toyooka, MD Medical Oncology/Pulmonary Medicine Thoracic Surgery/Translational Research China Japan EDITORIAL BOARD Gouri Shankar Bhattacharyya, MD Ronan Kelly, MD Yoshitaka Sekido, MD, PhD India USA Japan Thierry Berghmanns, MD Takashi Kohno, PhD Lecia Sequist, MD Belgium Japan USA Paolo Bironzo, MD Natasha Leighl, MD Patrick Nana-Sinkam, MD, FCCP Italy Canada USA Lukas Bubendorf, MD Aaron Mansﬁeld, MD, PhD Pawan Kumar Singh, MD, DM Switzerland USA India Mauricio Burotto, MD Tamas F. Molnar, PhD, DSc Thomas Stinchcombe, MD Chile Hungary USA Samjot Singh Dhillon, MD Kaushal Parikh, M.B.B.S. Shalini Vinod, MD USA USA Australia Jessica Donington, MD Nir Peled, MD, PhD Fen Wang, MD USA Israel China Afshin Dowlati, MD Paola Perego, PhD Shuhang Wang, MD USA Italy China Nicolas Girard, MD, PhD Helmut Popper, MD Pan-Chyr Yang, MD France Austria Taiwan Heidi A. Hamann, PhD Jordi Remon, MD Sai Yendamuri, MD USA Spain USA Lizza E Hendriks, MD, PhD Thanyanan Reungwetwattana, MD Junji Yoshida, MD, PhD Netherlands Thailand Japan Andreas-Claudius Hoffmann, MD Jeon-Seong Ryu, MD, PhD Matjaž Zwitter, MD, PhD Germany South Korea Slovenia IASLC BOARD OF DIRECTORS

Tetsuya Mitsudomi Enriqueta Felip Nir Peled President Spain Israel Japan [email protected] [email protected] [email protected] Anne Fraser Suresh Ramalingam Heather Wakelee New Zealand US President Elect [email protected] [email protected] US [email protected] Roy Herbst Erik Thunnissen US Netherlands Giorgio V. Scagliotti [email protected] [email protected] Past President Italy Clarissa Mathias Paul E. Van Schil [email protected] Brazil Belgium Dave Mesko [email protected] [email protected] CEO Yuko Nakayama James Yang US Japan Taiwan [email protected] [email protected] [email protected] Andrea Bezjak Canada Masayuki Noguchi Caicun Zhou [email protected] Japan China [email protected] [email protected] Julie Brahmer US [email protected] Notice: The content of the abstracts contained in this Abstract Book is subject to embargo.

Abstracts accepted for presentation at ELCC 2021 Virtual as Proffered Paper (suffix ‘O’), Mini Oral (suffix ‘MO’) and e-Poster (suffix ‘P’ and ‘TiP’) will be published online on the ELCC 2021 Virtual website at 12:00hrs Central European Time (CET) on Wednesday, 17 March 2021. Abstracts selected for the official ELCC 2021 Virtual Press Programme (additional suffix ‘_PR’) will be made public at the beginning of the official ELCC 2021 Virtual Press Conference or the official Congress session during which they are presented, whichever comes first. Disclaimer: No responsibility is assumed by the organizers for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. Because of the rapid advances in medical sciences, assumedwe recommend by the thatorganisers independent for any verification omissions orof misprints.diagnoses and drug dosages should be made. Every effort has been made to faithfully reproduce the abstracts as submitted. However, no responsibility is Official Journal of the International Association for the Study of Lung Cancer (IASLC)

Volume 16, Issue 4S, Supplement, April 2021

TABLE OF CONTENTS

Abstract Book of the European Lung Cancer Virtual Congress (ELCC 2021 Virtual) 25–27 March 2021

European Society for Medical Oncology (ESMO) viii International Association for the Study of Lung Cancer (IASLC) ix European SocieTy for Radiotherapy and Oncology (ESTRO) x European Society of Thoracic Surgeons (ESTS) xi European Thoracic Oncology Platform (ETOP) xii European Lung Cancer Virtual Congress 2021 Organisation xiii European Lung Cancer Virtual Congress 2021 Officers xiii

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Journal of Thoracic Oncology (ISSN 1556-0864) is published monthly by Elsevier Inc., without notice. Information and prices regarding single copies and special orders are 230 Park Avenue, New York, NY 10169. available upon request. Postmaster: Send address changes to Journal of Thoracic Oncology, Elsevier Inc., 3251 Copyright: 20201 International Association for the Study of Lung Cancer. Published by Riverport Lane, Maryland Heights, MO 63043. Elsevier Inc. This journal and the individual contributions contained in it are protected Customer Service: Address orders, claims, change of address to: Please visit our under copyright, and the following terms and conditions apply to their use in addition to Support Hub page https://service.elsevier.com for assistance. Address changes must be the terms of any Creative Commons or other user license that has been applied by the submitted four weeks in advance. publisher to an individual article: Annual Subscription Rates: United States and Canada: Personal, $925.00; All other countries: Personal, $924.00. Prices include postage and are subject to change

Submitted Abstracts Tumour biology and pathology S699 Translational research S704 Prevention, Early detection, Epidemiology, Tobacco control S711 Imaging and staging S717 SCLC S720 Early stage NSCLC S729 Locally advanced NSCLC S737 Advanced NSCLC S748 Metastases to and from the lung S803 Mesothelioma S805 General interest S808

Author Index S815

Note: Abstract suffixes “O” indicates a submitted abstract accepted for oral presentation “MO” indicates a submitted abstract accepeted for mini oral presentation “P” indicates a submitted abstract accepted for poster presentation “TiP” indicates a submitted “Trial in Progress” abstract selected for poster presentation

“_PR” indicates a submitted abstract selected for press coverage

Photocopying: Single photocopies of single articles may be made for personal use as Notice: The statements and opinions contained in the material herein are solely those allowed by national copyright laws. Permission is not required for photocopying of of the individual authors and contributors and not those of the International Associ- articles published under the CC BY license nor for photocopying for non-commercial ation for the Study of Lung Cancer or Elsevier Inc. Practitioners and researchers must purposes in accordance with any other user license applied by the publisher. always rely on their own experience and knowledge in evaluating and using any Permission of the publisher and payment of a fee is required for all other information, methods, compounds or experiments described herein. Because of rapid photocopying, including multiple or systematic copying, copying for advertising or advances in the medical sciences, in particular, independent veriﬁcation of diagnoses promotional purposes, resale, and all forms of document delivery. Special rates are and drug dosages should be made. To the fullest extent of the law, no responsibility is available for educational institutions that wish to make photocopies for non-proﬁt assumed by the publisher or the IASLC for any injury and/or damage to persons or educational classroom use. property as a matter of products liability, negligence or otherwise, or from any use or Derivative Works: Users may reproduce tables of contents or prepare lists of articles including operation of any methods, products, instructions or ideas contained in the material abstracts for internal circulation within their institutions or companies. Other than for articles herein. Although all advertising material is expected to conform to ethical (medical) published under the CC BY license, permission of the publisher is required for resale or dis- standards, inclusion in this publication does not constitute a guarantee or endorsement tribution outside the subscribing institution or company. of the quality or value of such product or of the claims made of it by its manufacturer. For any subscribed articles or articles published under a CC BY-NC-ND license, Reprints: To order 100 or more reprints for educational, commercial, or promotional permission of the publisher is required for all other derivative works, including use, please contact Derrick Imasa, Commercial Reprints Department, Elsevier Inc., 230 compilations and translations. Park Avenue, New York, NY 10169; phone (212) 633-3874; fax (212) 462-1935; e-mail: Storage or Usage: Except as outlined above or as set out in the relevant user license, no [email protected]. part of this publication may be reproduced, stored in a retrieval system or transmitted in For advertising orders and inquiries: North and South America: Courtney Leonard, any form or by any means, electronic, mechanical, photocopying, recording or otherwise, Elsevier Inc., 230 Park Avenue, New York, NY 10169; phone (732) 779-3368; e-mail: c. without prior written permission of the publisher. [email protected]. Europe/ROW: Robert Bayliss, Elsevier Inc., 125 London Wall, Permissions: For information on how to seek permission visit www.elsevier.com/ London, EC2Y 5AS, UK; phone (+44) (20) 7424 4454; e-mail: [email protected]. permissions or call: (+44) 1865 843830 (UK) / (+1) 215 239 3804 (USA). Journal of Thoracic Oncology is indexed in Current Contents/Clinical Medicine, Science Author rights: Author(s) may have additional rights in their articles as set out in their Citation Index Expanded (SCIE), Journal Citation Reports/Science Edition, and agreement with the publisher (more information at http://www.elsevier.com/authorsrights). MEDLINE. ELCC 2021 Virtual Journal of Thoracic Oncology Vol. 16, Suppl. 4S (2021) viii

European Society for Medical Oncology (ESMO)

ESMO is the leading professional organisation for medical oncology. With more than 25,000 members representing oncology professionals from over 160 countries worldwide, ESMO is the society of reference for oncology education and information. ESMO is committed to offer the best care to people with cancer, through fostering integrated cancer care, supporting oncologists in their professional development, and advocating for sustainable cancer care worldwide. Founded in 1975, ESMO has European roots with a global reach. Home for all oncology stakeholders, ESMO connects professionals with diverse expertise and experience. Its education and information resources support an integrated multi-professional approach to cancer care, from a medical oncology perspective. ESMO seeks to erase boundaries in cancer care, whether between countries or specialities, and pursue its mission across oncology, worldwide. members and the oncology community through: •Drawing• on more than 40 years of experience and around 800 expert committee members, ESMO serves its •• •• Post-graduate oncology education and training Career development and leadership training for the next generations of oncologists •• International congresses and workshops to share expertise and best practice, learn about the most up- •• to-date scientific advances, and connect with colleagues in related disciplines Continuously reviewed, evidence-based standards for cancer care Advocacy and consultation to foster a favourable environment for scientific research Cancer care is rapidly becoming more integrated and more specialised; whether their field is research, possible.diagnosis, treatment, care, or advocacy, oncology professionals need to both build their specialist knowledge and connect with the best practitioners in other disciplines worldwide. ESMO membership makes this www.esmo.org ELCC 2021 Virtual Journal of Thoracic Oncology Vol. 16, Suppl. 4S (2021) ix

International Association for the Study of Lung Cancer (IASLC)

The IASLC is the only global organization dedicated solely to the study of lung cancer and

other thoracic malignancies. Founded in 1974, the association's membership includes nearly 7,500 lung cancer specialists across all disciplines in more than 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The treatmentassociation of also all thoracic publishes malignancies. the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and www.iaslc.org ELCC 2021 Virtual Journal of Thoracic Oncology Vol. 16, Suppl. 4S (2021) x

European SocieTy for Radiotherapy and Oncology (ESTRO)

ESTRO, the European SocieTy for Radiotherapy & Oncology, is a scientific non-profit organisation whose ambition is to further reinforce radiation oncology as a core partner in multidisciplinary cancer care and to guarantee accessible and high-value radiation therapy for all cancer patients who need it. ESTRO’s mission is to promote education, science, research and advocate for access to radiotherapy. Throughout the year, the Society organises an annual Congress, teaching courses, workshops, and public affairs activities and publishes scientific material in its family of journals. www.estro.orgThe Society counts over 7,600 members in and outside Europe and supports all the radiation oncology professionals and the wider oncology community in their daily practice. ELCC 2021 Virtual Journal of Thoracic Oncology Vol. 16, Suppl. 4S (2021) xi

European Society of Thoracic Surgeons (ESTS)

ESTS is the largest international general thoracic surgery organization with over 1600 members from all Continents. Our mission is to improve quality in all aspects of our specialty: from clinical and surgical management of patients to education, training and credentialing of thoracic surgeons worldwide. ESTS Membership fees are tiered according to the average per capita income of the country in which surgeons practice. Access to the European Journal of Cardiothoracic Surgery Membership benefits include:

EligibilityReduced registration to join the ESTS to the Database ESTS Annual Meeting Reduced registration to ESTS educational activities

The 29th European Virtual Conference on General Thoracic Surgery will be held on the 20–22 June 2021. The outstanding program will provide high quality scientific education with live presentations and discussions using an interactive and innovative digital platform. CME for delegates watching live and sessions available on demand following the meeting. The ESTS School of Thoracic Surgery was established in 2007 with the aim of providing educational platforms for thoracic surgeons worldwide. Educational webinars offering a wide range of topics with worldwww.ests.org renown experts are offered free. ELCC 2021 Virtual Journal of Thoracic Oncology Vol. 16, Suppl. 4S (2021) xii

European Thoracic Oncology Platform (ETOP)

ETOP is a not-for-profit organization promoting academic clinical research and the exchange of ideas in the field of thoracic oncology. It sponsors and manages an increasing number of translational research projects and clinical trials with an emphasis on advancing the knowledge in thoracic malignancies. ETOP comprises more than 50 collaborative groups and institutions from all over Europe and beyond. •• Thethoracic specific malignancies aims of ETOP are: •• To foster serve intergroup as a meeting studies platform among for institutions European and study study groups groups and across institutions Europe engaged and beyond in research on •• •• •• To sponsor and/or perform own studies and clinical trials To foster scientific exchange on clinical and translational research among interested parties and beyond www.etop-eu.orgTo provide knowledge to partners in the field ELCC 2021 Virtual Journal of Thoracic Oncology Vol. 16, Suppl. 4S (2021) xiii

European Lung Cancer Virtual Congress 2021 Organisation

Organisation ESMO Head Office Via Ginevra 4 CH-6900 Lugano [email protected] Tel. +41 (0)91 973 19 62

European Lung Cancer Virtual Congress 2021 Officers

Scientific Committee Co-Chairs

DavidScientific Planchard, Committee Villejuif, Honorary France (ESMO)Co-Chairs Enriqueta Felip, Barcelona, Spain (IASLC)

Corinne Faivre-Finn, Manchester, UK (ESMO) Fabrice Barlesi, Villejuif, France (IASLC) Steering Committee

Solange Peters, Lausanne, Switzerland (ESMO) Tetsuya Mitsudomi, Osaka, Japan (IASLC) George Pentheroudakis, Lugano, Switzerland (ESMO) Heather Wakelee, Stanford, CA, USA (IASLC) Scientific Committee

Myung-Ju Ahn, Seoul, Republic of Korea Yolande Lievens, Ghent, Belgium Julie Brahmer, Baltimore, MD, USA Julien Mazières, Toulouse, France Alessandro Brunelli, Leeds, UK Luis Paz-Ares, Madrid, Spain Reinhard Büttner, Cologne, Germany Umberto Ricardi, Turin, Italy Federico Cappuzzo, Rome, Italy Ross Soo, Singapore Anne-Marie Dingemans, Rotterdam, Netherlands Rolf A. Stahel, Zurich, Switzerland Rafal Dziadziuszko, Gdansk, Poland Pascal Thomas, Marseille, France John Edwards, Sheffield, UK Judith van Loon, Maastricht, Netherlands Marina Garassino, Milan, Italy Paul Van Schil, Edegem, Belgium Nicolas Girard, Paris, France James Yang, Taipei, Taiwan Alastair Greystoke, Newcastle upon Tyne, UK Yasushi Yatabe, Tokyo, Japan Norihiko Ikeda, Tokyo, Japan Caicun Zhou, Shanghai, China Natasha Leighl, Toronto, ON, Canada

Acknowledgements

ESMO and IASLC wish to express their appreciation and gratitude to the ELCC 2021 Virtual Scientific and Steering Committees for their major effort in reviewing the abstract content of this Abstract Book. Acknowledgements

ESMO and IASLC gratefully acknowledge the valuable contribution the following organisations have made to the European Lung Cancer Virtual Congress 2021 (ELCC 2021 Virtual):

PLATINUM SPONSORS

GOLD SPONSORS

SILVER SPONSORS

BRONZE SPONSORS

SPONSORS

Product promotion at ESMO events Advertising/promotion of a specific product/service does not mean acceptance by ESMO and IASLC. It is the full responsibility of the ELCC 2021 Virtual sponsors to respect the Code of Practice governing the promotion of their products/services. The ELCC organisers accept no responsibility for misprints. Sponsors as of 22 February 2021. ABSTRACTS

Conclusions: Three real-world databases identified the near loop as the TUMOUR BIOLOGY AND PATHOLOGY most frequent insertion region of Exon 20 (∼70%). Exon20ins mutations were found less frequently in the far loop (∼30%) and helical (0–7.5%) regions 1P Editorial acknowledgement: Medical writing support was provided by Real-world frequency of non-small cell lung cancer with Tracy T. Cao, PhD of Janssen Global Services, LLC and funded by Janssen epidermal growth factor receptor (EGFR) exon 20 insertion Global Services, LLC. (Exon20ins) mutations by site of insertion Legal entity responsible for the study: Janssen R&D. Funding: Janssen R&D. 1 2 3 4 5 S. Viteri , J.M. Bauml , L. Bazhenova , S-H.I. Ou , N. Girard , Disclosure: S. Viteri: Advisory/Consultancy: Roche, BMS, Janssen; Speaker M. Schaffer6, J. Rose6, J. Curtin6, J. Karkera6, P. Mahadevia6, Bureau/Expert testimony: Roche, BMS, AstraZeneca; Travel/Accommodation/ A.R. Minchom7 1Instituto Oncologicó Dr Rosell, Centro Medicó Teknon, Expenses: MSD. J.M. Bauml: Advisory/Consultancy: Clovis, BMS, AstraZeneca, Celgene, Boehringer Ingelheim, Janssen, Merck, Guardant Health, Genentech, Grupo QuironSalud, Barcelona, Spain; 2Perelman School of Medicine at the 3 Takeda, Ayala, Regeneron, Inivata, Novartis; Research grant/Funding (institution): University of Pennsylvania, Philadelphia, PA, USA; University of California Merck, Clovis, Carevive Systems, Novartis, Bayer, Janssen, AstraZeneca, Takeda. San Diego, La Jolla, CA, USA; 4University of California Irvine, Orange, CA, L. Bazhenova: Advisory/Consultancy: J&J, Daichi, BI, BMS, Merk, Novartis, USA; 5Institut Curie, Paris, France; 6Janssen R&D, Spring House, PA, USA; Regeneron, Genentech; Research grant/Funding (institution): Beyondspring; 7 Shareholder/Stockholder/Stock options: Epic Sciences. S-H.I. Ou: Speaker Drug Development Unit, Royal Marsden/Institute of Cancer Research, Bureau/Expert testimony: Roche/Genentech, Takeda/ARIAD, AstraZeneca, London, UK Merck, Pfizer; Advisory/Consultancy: Pfizer, AstraZeneca, Takeda/ARIAD, Roche/Genentech, AnHeart Therapeutics; Shareholder/Stockholder/Stock Background: EGFR Exon20ins mutations are in-frame insertions or options: Turning Point Therapeutics, Elevation Oncology. N. Girard: Advisory/ duplications clustered around 3 key regions of Exon 20: helical (amino Consultancy: Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Pfizer, acid [AA] 762–766), near loop (767–772), and far loop (773–775). The Amgen, Takeda, Boehringer Ingelheim, Roche; Research grant/Funding (institution): Bristol-Myers Squibb, Boehringer Ingelheim, Roche, Janssen. M. Schaffer: site of insertion can influence the outcome to EGFR tyrosine kinase Shareholder/Stockholder/Stock options: Johnson & Johnson; Full/Part-time inhibitor therapy; loop insertions are typically resistant while some employment: Janssen. J. Rose: Shareholder/Stockholder/Stock options: Johnson helical insertions are sensitive (Yasuda Lancet Oncol 13:23; Sci Transl and Johnson; Full/Part-time employment: Janssen Inc. J. Curtin: Shareholder/ Med 5:216ra177). We used real-world US genomic data from patients Stockholder/Stock options: Johnson & Johnson; Full/Part-time employment: Janssen. J. Karkera: Shareholder/Stockholder/Stock options: Johnson & Johnson; (pts) with lung adenocarcinoma (LUAD) to determine the frequency of Full/Part-time employment: Janssen. P. Mahadevia: Shareholder/Stockholder/ EGFR Exon20ins mutations by site of insertion. Stock options: Johnson & Johnson; Full/Part-time employment: Janssen. A.R. Methods: Pts with EGFR Exon20ins mutations identified from US Minchom: Honoraria (self): Janssen Pharmaceutica, Meck Pharmaceuticals, institutions by next-generation sequencing were extracted from the Novartis Oncology, Faron Pharmaceuticals, Bayer Pharmaceuticals; Travel/ Accommodation/Expenses: LOXO oncology, Amgen Pharmaceuticals. AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE), v.8.5 (Cancer Discov 2017;7:818), FoundationInsights, and Guardant databases. Results: From GENIE, 175/9,673 pts (1.8%) with LUAD had EGFR 2P Exon20ins mutations: 72.0% were located in the near loop, 28.0% in the Role of neutrophil-to-lymphocyte ratio (NLR) in the outcome far loop, and none in the helical region (Table). The most frequent sites of NSCLC EGFR mutated of insertion were AAs 770 (36.0%), 773 (26.9%), and 769 (21.7%). From FoundationInsights, 627/36,465 pts (1.7%) with LUAD had EGFR S. Tolu1, G. Saba2, V. Impera1, D. Spanu2, N. Liscia1, G. Pinna2, Exon20ins mutations: 67.8% were located in the near loop, 26.6% in the A. Pireddu1, L. Demurtas2, E. Lai2, F. Manca2, C. Madeddu2, far loop, and 5.4% in the helical region. The most frequent sites of E. Massa2, G. Astara2, M. Scartozzi2 1Oncologia Medica, University of insertion were AAs 770 (28.1%), 769 (23.4%), and 773 (22.8%). One Cagliari - Sapienza Universitàdi Roma, Monserrato, Italy; 2Oncologia Exon20ins mutation at AA 793 was also identified (Table). From Medica, University of Cagliari, Monserrato, Italy Guardant, 414/31,617 pts (1.3%) with LUAD had EGFR Exon20ins mutations. 65.9% were located in the near loop, 26.6% in the far loop, Background: Systemic inflammation promotes angiogenesis and cell and 7.5% in the helical region (Table). The most frequent sites of proliferation, which play key roles during carcinogenesis. Several studies insertion were AAs 770 (28.0%), 769 (24.2%), and 773 (22.9%). have shown a strong link between inflammation index and prognosis in non-small cell lung cancer (NSCLC). The aim of our study is to investigate the role of NLR at diagnosis in the outcome of NSCLC EGFR mutated. Table 1P: Exon20ins mutations by site of insertion Methods: Our retrospective analysis included 103 eligible patients Insertion region of Exon GENIE FoundationInsights Guardant (pts), including 40 pts with EGFR wild type (wt) NSCLC and 63 pts with 20, n (%) (N = 175) (N = 627) (N = 414) EGFR mutated NSCLC. Inclusion criteria were over 18 years of age, Helical (AA 762–766) 0 34 (5.4) 31 (7.5) diagnosis of NSCLC, availability of a pre-treatment complete blood count. 763 0 33 (5.3) 31 (7.5) Exclusion criteria were active infections, autoimmune diseases, use of 764 0 1 (0.2) 0 corticosteroids. The NLR was derived from the absolute neutrophil and Near Loop (AA 767–772) 126 (72.0) 425 (67.8) 273 (65.9) the absolute lymphocyte counts. The cutoff value was determined 767 1 (0.6) 5 (0.8) 2 (0.5) through the use of ROC curves and through the distinction, based on 768 0 13 (2.1) 2 (0.5) overall survival (OS) at 12 months, between pts with good and bad 769 38 (21.7) 147 (23.4) 100 (24.2) prognosis. For each subgroup of mts, median OS was assessed. Statistical 770 63 (36.0) 176 (28.1) 116 (28.0) 771 17 (9.7) 66 (10.5) 35 (8.5) processing was performed with the aim of correlating the haemato- 772 7 (4.0) 18 (2.9) 18 (4.3) logical data collected with the clinical outcome. Far Loop (AA 773–775) 49 (28.0) 167 (26.6) 110 (26.6) Results: In pts EGFR wt the NLR cut-off obtained was 3.18., in pts EGFR 773 47 (26.9) 143 (22.8) 95 (22.9) mutaded the cut-off was 3,5. Pts who have a value less than or equal to 774 1 (0.6) 17 (2.7) 15 (3.6) cut-off have a better prognosis, compared to pts who have a NLR higher 775 1 (0.6) 7 (1.1) 0 than have a worse prognosis. As a pts EGFR wt the median best OS was Other Regions (AA 776– 0 1 (0.2) 0 41.33 months, while the worst OS was a median of 10.33 months, with a 823) difference of 31 months (p = 0.0003). In case of pts EGFR mutaded the 793 0 1 (0.2) 0 best median OS was 21 and the worst 8,3 months, with a difference of 13

Journal of Thoracic Oncology Vol. 16 No. 4S: S699–S703 S700 Journal of Thoracic Oncology Vol. 16 No. 4S months (p = 0,013). There were no significant differences in age, ECOG PS, histology, size, therapies or treatment line. 4P Conclusions: The NLR remains a prognostic factor in both diseases, with Prevalence of METexon 14-mutations or MET amplification in or without EGFR mutation, but appear to have less impact on the non-small cell lung cancer in Swiss patients outcome of EGFR mutated patients. In NSCLC EGFR mutated maybe inflammatory index could have implications on therapeutic choice, S. Savic Prince1, M. Bihl1, S. Eppenberger-Castori1, M.S. Matter1, especially subsequent lines and his role deserves further study. N. Zellweger2, S.I. Rothschild2, L. Bubendorf1 1Pathology, Institute of Legal entity responsible for the study: Mario Scartozzi. Medical Genetics and Pathology, University Hospital Basel, Basel, Funding: Has not received any funding. Switzerland; 2Department of Oncology, University Hospital Basel, Basel, Disclosure: All authors have declared no conflicts of interest. Switzerland Background: MET-targeted treatment has improved by the introduction 3P of highly selective MET inhibitors for advanced stage MET Exon 14- AZ12756122, a novel fatty acid synthase (FASN) inhibitor, mutated or MET-amplified non-small cell lung cancer (NSCLC). MET exon 14 skipping mutations occur in 3% and MET amplification in 1 to reduces resistance properties in gefitinib- and osimertinib- 6% of unselected NSCLC. The aim of our study was to investigate the resistant EGFR-mutated non-small cell lung cancer models prevalence of these MET alterations in treatment-naïve pre-selected

1 1 2 2 NSCLC from our routine clinical practice, were MET analyses were E. Polonio , S. Palomeras , R. Porta-Balanya , J. Bosch-Barrera , generally performed sequentially in NSCLC with high MET expression ́ 3 4 ı́ 1 1 1 C.A. Vasquez , J. Ciurana , S. Ruiz-Mart nez , T. Puig Medical and wild type status for EGFR, KRAS, ALK and ROS1. 2 Sciences Dept., University of Girona, Girona, Spain; Medical Oncology, ICO Methods: 580 consecutive treatment-naïve NSCLC who underwent ̀’ 3 Girona - Institut Catala d Oncologia Girona, Girona, Spain; Servei routine predictive testing were retrospectively evaluated. High MET d’Anatomia Patologica,̀ Institut Catalàde la Salut, Girona, Spain; 4 expression, as determined by immunohistochemistry (IHC), was defined Mechanical Engineering and Industrial Construction Department, as complete membranous MET staining with at least moderate intensity University of Girona, Girona, Spain in ≥50% of tumor cells. MET exon 14 analysis was performed by Sanger Background: Non-small cell lung cancer (NSCLC) is the most common sequencing. MET gene copy numbers were evaluated by fluorescence in subtype corresponding to roughly 85% of lung cancer patients. The situ hybridization (FISH) and MET amplification was defined as a MET/ ≥ discovery of activating mutations in the epidermal growth factor receptor CEN7 ratio of 2.0. MET IHC was performed on histology specimens and (EGFRm) gene has led to an era of targeted therapy in lung cancer with cellblocks, but not on conventional cytology preparations. Therefore, EGFR tyrosine kinase inhibitors (TKIs). Although great progress has been prevalence data of MET alterations were analyzed separately for IHC pre- accomplished, therapeutic improvement is necessary due to the constant selected and non-preselected NSCLC wild type for other oncogenic appearance of resistance. Cancer stem cells (CSCs) are a small subpopula- driver alterations. tion responsible for tumour initiation and progression, recurrence, Results: 66% (302/457) of NSCLC had high MET expression. There was metastasis, and resistance to anti-cancer therapies. Furthermore, the no difference between the prevalence of MET exon 14 mutations in IHC overexpression and hyperactivation of fatty acid synthase (FASN) has been pre-selected and non-preselected NSCLC wild type for other oncogenic related to tumour aggressiveness and therapy resistance. Previously, we driver alterations (8.3% (9/108) and 8.1% (7/86), respectively, p = 1.0). have shown that FASN inhibition causes cytotoxic effects in EGFRm lung In contrast, the prevalence of MET amplification was higher in MET adenocarcinoma cell models sensitive and resistant to EGFR-TKIs. IHC pre-selected NSCLC (11.5% (11/96) and 3.2% (1/31), respectively, Additionally, the combination of AZ12756122, a novel FASN inhibitor, p = 0.29). with osimertinib exhibited a synergistic interaction. Therefore, we studied Conclusions: MET exon14 skipping mutations are enriched in NSCLC the effect of AZ12756122in combinationwith osimertinib on EGFR, HER2, wild type for other oncogenic driver alterations with the prevalence of MAPK, STAT3 and AKT proteins in EGFRm NSCLC models sensitive and >8% being higher compared to the published literature in unselected resistant to EGFR-TKIs. Moreover, the ability of AZ12756122 to target the NSCLC (3%). High MET expression does not enrich for MET exon 14 CSC population was evaluated. mutations. However, MET IHC seems to be a cost-effective approach for Methods: EGFRm lung adenocarcinoma models sensitive to EGFR-TKIs pre-screening NSCLC for further MET FISH analysis. (PC9) and T790M- resistant to both gefitinib and osimertinib (PC9-GR3) Legal entity responsible for the study: The authors. were used. Gene and protein expression were assessed through qRT-PCR Funding: Has not received any funding. and Western blot, respectively. CSC population was evaluated by means Disclosure: S. Savic Prince: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self): Roche; Honoraria (self), Advisory/Consultancy: AstraZeneca. S.I. of sphere-formation and clonogenic assays. Rothschild: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Results: The combination of AZ12756122 with osimertinib reduced Advisory/Consultancy: Pfizer; Advisory/Consultancy: Takeda; Advisory/ FASN protein expression and the EGFR, HER2, AKT, MAPK, and STAT3 Consultancy: MSD Oncology; Advisory/Consultancy: Novartis; Advisory/ protein activation in the PC9-GR3 model. AZ12756122 treatment Consultancy, Research grant/Funding (self): Boerhinger-Ingelheim; Advisory/ Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Eli Lilly; Advisory/ decreased the CSC properties tested of PC9 and PC9-GR3 models. Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (self): Meck Conclusions: In conclusion, FASN inhibition caused by AZ12756122 Serono; Research grant/Funding (self): AbbVie; Advisory/Consultancy: Amgen; arises as an encouraging therapeutic alternative to overcome resistance Advisory/Consultancy: PharmaMar; Advisory/Consultancy, Research grant/ to EGFR-TKIs due to its synergistic interaction with osimertinib and its Funding (institution): Roche. L. Bubendorf: Honoraria (self), Advisory/ Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): capacity to reduce CSC properties in EGFRm NSCLC cell models. Roche. All other authors have declared no conflicts of interest. Legal entity responsible for the study: University of Girona. Funding: AstraZeneca. Disclosure: All authors have declared no conflicts of interest. April 2021 Abstracts S701

in both tumorigenesis and the progression of disease and it represents 5P an attractive target for novel anticancer therapies in NSCLC. False positive errors in RNA based next generation sequencing Methods: We performed a retrospective study of patients with NSCLC ́ of exon 14 skipping mutations in NSCLC treated in Hospital Universitario Ramon y Cajal, with alterations in PIK3 pathway identified by NGS. Clinical characteristics and concurrent M. Suryavanshi1, S. Mattoo2,U.Batra2, S. Sharma2, D. Kumar2, mutations were described. A. Mehta2 1Molecular Diagnostics, Rajiv Gandhi Cancer Institute and Results: 1745 patients with lung carcinoma were treated in our Research Centre, Delhi, India; 2Rajiv Gandhi Cancer Institute and Research institution between 2011 to 2020. We analyzed 479 patients with NSCLC Centre, Delhi, India who underwent NGS and 61 patients (12.7%) were identified with alteration in PIK3 pathway (tissue NGS in 43 and blood-based NGS in 19 Background: Exon 14 skipping mutations are found in approximately patients). 57.3% of patients were diagnosed at IV stage. Most of them 3% of patients with NSCLC. Robust approaches for detection of MET exon were men (67%) with smoking history (13% non-smokers). The most 14 skipping events are crucial for treatment. About one-third of the common histological types were adenocarcinoma (42%) and squamous mutations occur between exons 13 and 14 at acceptor site of exon 14, and cell carcinoma (36%). 27% of tumors were PD-L1 negative and 25 two-thirds occur between exons 14 and 15 at donor site. In addition, MET patients had determination of tumor mutational burden (>10 mut/Mb in exon 14 skipping can result from large deletions that can span not only all 52%). PI3-kinase catalytic subunit alpha (PIK3CA) was the more of exon 14 but large portions of the intronic sequence. This mutation can common molecular finding (77% of patients): mutations exon 9 and be detected bysequencing of DNA or RNA or both. DNA based approaches 20 (82.5%), amplification (13.7%) and both (3.4%). We also found the alone are not able to detect more than 60% of these mutations. RNA based presence of mutations of PTEN (tumor suppressor that negatively sequencing detects the product of exon 14 skipping mutations which is regulates the PIK3/AKT/mTOR pathway) in 6.5% and TP 53 in 59% of “fusion” of exon 13 to 15 regardless of the underlying genomic event. patients. Other mutations were detected in 27 patients (44.2%): EGFR Most studies have favoured a RNA based approach. (8%), KRAS (8,1%), ALK rearrangement (3.2%), BRAF (1.6%), MET Methods: During the period from August 2017 to January 2021, a total (3.2%), FGFR (6.5%), CDKs (22.9%). of 231 samples of NSCL were assessed by routine clinical application of Conclusions: Our cohort shows that alteration in PI3 K pathway is more the Thermofischer Ion Torrent™ Oncomine™ Focus 52 gene Assay. frequent in men with smoking history NSCLC patients and is not Sequencing data were processed with the Ion Torrent Suite software. mutually exclusive to other mutations, that remark the relationship This assay detects MET mutations at 3′ end splice donor site by DNA between pathways. Clinical trials are needed to predict the potential sequencing and RNA sequencing for exon 13 and exon 15 fusion for exon clinical benefit from the use of PI3 K pathway inhibitors. 14 skipping mutation. All positive cases on RNA sequencing were Legal entity responsible for the study: The authors. reanalysed by PCR and Sanger sequencing for confirmation. Funding: Has not received any funding. Results: Exon 13 and exon 15 fusion by RNA was detected in 20 cases. Disclosure: All authors have declared no conflicts of interest. Read counts ranged from 143 to 7980. Two cases had additional MET amplification, one case had EGFR deletion 19,one case had CTNNB1 p. Ser37Phe and KRAS p.Gly12Asp, one case had RET KIF5B Fusion (read 7P count 458), one case had EGFR amplification and in remaining cases STK11 and Galectin-3 tissue expression entails a prognostic exon 13 and exon 15 fusion was the sole abnormality. Only 6 out of 20 signature in immunotherapy treated NSCLC patients cases detected by NGS were confirmed by Sanger sequencing. All cases above the read count of 1607 were detected by sanger sequencing. All G. Mazzaschi1, R. Minari1, L. Gnetti2, N. Campanini2, T. Zielli3, true positive cases had exon 3 and exon 15 fusion as the sole M. Baucina4, F. Perrone3, A. Leonetti3, F. Quaini5, M. Tiseo3 1Medical abnormality. Cases with MET amplification were also negative on Oncology Unit, University Hospital of Parma, Parma, Italy; 2Pathology, sanger sequencing. Azienda Ospedaliero-Universitaria di Parma, Parma, Italy; 3Medical Conclusions: RNA based exon 13 and exon 15 fusion for detection of Oncology, AOU di Parma, Parma, Italy; 4Medicine and Surgery, University exon 14 skipping mutations can have false positive calls by Ion torrent- Hospital of Parma, Parma, Italy; 5Medicine and Surgery Department, based sequencing and should be confirmed by alternate methods. Azienda Ospedaliero-Universitaria di Parma, Parma, Italy Legal entity responsible for the study: The authors. Funding: Rajiv Gandhi Cancer Institute and Research Center, Delhi, Background: The profound and long-lasting response to immune India. checkpoint inhibitors (ICIs) in a subset of non-small cell lung cancer Disclosure: All authors have declared no conflicts of interest. (NSCLC) patients makes it urgent the need of predictive biomarkers. As critical modulators of the tumor microenvironment, STK11 and Galectin-3 (Gal-3) demonstrated significant impact on patient 6P outcome. Thus, we aimed to dissect the prognostic and predictive role Clinical and molecular characteristics in non-small cell lung of STK11 and Gal-3 tissue expression in ICI-treated advanced NSCLC. cancer patients with alteration in PIK3 pathway Methods: Tissue and peripheral blood (PB) samples were collected at baseline from 25 consecutive NSCLC undergoing ICI. STK11 and Gal-3 Y. Lage1, P. Álvarez Ballesteros1, M.E. Olmedo Garcıá1, expression was detected by Immunohistochemistry (IHC). STK11 A. Gómez Rueda1, E. Corral de la Fuente1, J. Torres Jiménez1, mutation was determined by Next Generation Sequencing (NGS) in a E.M. Vida Navas1, J.J. Soto Castillo1, M. Lario2, A. Benito Berlinches2, subset of cases (n: 8, so far - other cases are ongoing). Soluble PD-L1 A. Santón2, P. Garrido Lopez1 1Medical Oncology Department, Hospital (sPD-L1) (immunoassay), PB CD8+PD1+ and NK cells (FACS) together Universitario Ramon y Cajal, Madrid, Spain; 2Pathology Department, with inflammatory features including LDH were measured. Tissue Hospital Universitario Ramon y Cajal, Madrid, Spain parameters were correlated with clinical outcome and circulating immune profile. Background: Currently non-small cell lung cancer (NSCLC) is a tumor Results: Absence of STK11 expression by IHC (STK11neg) was detected with a broad spectrum of targeted therapies already available or in in 18 (72%) NSCLC among which 74% were KRAS-mutant. Lack of clinical trials. Molecular characterization of the tumor using next STK11 expression at tissue and genomic levels was concordant in 62%. generation sequencing (NGS) technology has become a key tool for the STK11neg cases displayed a trend towards a worse PFS (median PFS molecular profiling of NSCLC, facilitating treatment decisions. The [mPFS], 4.3 vs 13.5 months, P = 0.09) and OS (median OS, 12.8 months phosphoinositide-3-kinase (PI3 K) signaling pathway has a critical role vs not reached, P = 0.190). Although PFS was shorter in Gal-3high (2+/3+ S702 Journal of Thoracic Oncology Vol. 16 No. 4S

IHC) cases, Gal-3 status did not impact on OS nor DCR. Significantly microbiome composition of SSN is distinct from that of SN. Subsolid lung higher sPD-L1 levels (P = 0.037) and lower circulating NK (P = 0.042) adenocarcinoma has a special microbiome subtype. were observed in STK11neg cases, while Gal-3high were associated to Legal entity responsible for the study: Peking University People’s higher LDH values and lower CD3+ and NK. Patients carrying STK11neg/ Hospital. Gal-3high tumors had significantly reduced PFS (mPFS, 1.7 vs 13.5 Funding: National Natural Science Foundation of China. months, P = 0.001) and lower benefit from ICI (DCR, 30% vs 80%, P = Disclosure: All authors have declared no conflicts of interest. 0.03) compared to their counterpart. Moreover, STK11neg/Gal-3high signature had a relevant impact on CD4+, CD8+ and NK number and LDH levels. neg high 9P Conclusions: STK11 and Gal-3 may represent a poor prognostic Lung cancer mutational state assessed by NGS in a Portuguese trait in ICI-treated NSCLC patients. The correlation of STK11 and center Galectin with circulating factors underlies a close interplay between tissue and peripheral blood compartments, ultimately featuring the D. Magalhães1, M. Vilaça1, É. Cipriano1, A. Tavares1, D. Silva1, tumor-host interaction and the proneness to respond to ICIs. L. Cirnes2, H. Magalhães1, F. Estevinho1 1Oncology Department, ULS Legal entity responsible for the study: University Hospital of Parma. Matosinhos - Hospital Pedro Hispano EPE - SNS, Senhora da Hora, Funding: Has not received any funding. Portugal; 2Institute of Molecular Pathology and Immunology of the Disclosure: All authors have declared no conflicts of interest. University of Porto (IPATIMUP), Porto, Portugal Background: In advanced non-squamous non-small cell lung cancer 8P (NSCLC), and other selected NSCLC patients molecular testing is crucial Distinct tumor bacterial microbiome in lung adenocarcinomas to detect oncogenic driver mutations and to direct treatment regarding manifested as radiological subsolid nodules the molecular profile. Next-generation sequencing (NGS) allows accurate and efficient multiple genes and mutation analyses. This technique offers an extensive molecular tumor characterization in a cost-effective Y. Ma, M. Qiu Thoracic Surgery, Peking University People’s Hospital, and timely manner. Our aim was to evaluate the NGS mutational profile Beijing, China and to correlate the results with clinicopathological characteristics and Background: Early stage lung adenocarcinoma (LUAD) manifested as PD-L1 expression in patients with NSCLC. subsolid nodules (SSN) in CT have been considered as a special clinical Methods: Retrospective study of the NGS analysis, carried out in subtype and are less aggressive than pure solid LUAD. Here, we firstly patients (pts) with NSCLC between January 2017 and December 2020 in report the microbiome diversity between subsolid and solid LUAD. our oncological center in Portugal. Clinicopathological characteristics Methods: We performed 16S rRNA sequencing of 35 pairs of LUAD were accessed by review of medical records. A descriptive analysis was tumor tissues and adjacent normal tissues, including 10 SSN and 25 SN. performed, and Qui square was used to compare categorical variables. P- 29 patients were at TNM stage I, 2 were at TNM stage II, and 4 at were value reported was two-sided, and tests were conducted at the 0.05 TNM stage IIIA. Age, gender, BMI and TNM stage were matched between significance level, SPSS®20. SSN and SN. Machine learning was used to identify microbial signatures Results: A total of 299 pts with NSCLC were analyzed, 293 had a valid and construct predictive models. test. The median age was 69 years. 71% (n = 211) were males, 21% (n = Results: SSN and SN had 102 and 232 unique OTUs, respectively; while 62) were non-smokers and 33% (n = 99) were smokers. 65% (n = 190) tumor and normal lung tissues had almost identical OTUs. Interestingly, of the pts had at least one mutation. 73 pts (38%) had a mutation with a at phylum level, both SSN and SN were mainly composed of therapeutic target approved by EMA. KRAS was the most found mutation Actinobacteria, Proteobacteria, Firmicutes, and Bacteroidetes. SSN had (31%), followed by EGFR (14%) and ALK (5%). EGFR, ALK, ROS1 and significantly higher abundance of Chloroflexi and Gemmatimonadetes. RET were more prevalent in females (p < 0.05), KRAS was more At genus level, Rhodococcus, Ochrobactrum are main compositions in common in males. EGFR and RET were more common in pts younger these two groups. For alpha-diversity, SSN group has greater bacterial than 50 years old (p < 0.05). EGFR was most found in non-smokers, richness (number of OTUs, p = 0.017) and diversity (shannon index, p = KRAS was the most prevalent in smokers and former smokers (p < 0.17). Both the unweighted unifrac and PCoA analyses confirmed SSN 0.05). Regarding tumor PD-L1 expression, BRAF and MET variants were and SN have statistically different microbiome composition (Anosim, R = more common in PD-L1 ≥50% (p < 0.05), while EGFR was more 0.213, p = 0.016). Moreover, LEfSe analysis revealed 54 features that common in PD-L1 <50% (p < 0.05). may discriminate SSN and SN (LDA >2.5, p < 0.05). At genus level, Conclusions: KRAS and EGFR prevalence were in accordance with the increased bacteria such as Cloacibacterium, Subdoligranulum, and previous reported in Caucasian population. Some mutations correlate Mycobacterium and decreased bacteria like Lachnoclostridium were with clinic-pathological characteristics as sex, smoking status, and PD-L1 strong discriminative features for SSN. Probiotics with anti-cancer expression. Our study provides results from broad molecular profiling of potential, like Lactobacillus, showed elevated levels in normal Portuguese NSCLC pts treated in one hospital. In the future, multicentre tissues. Based on a five genera-signature, SSN could be accurately data analysis will be presented. discriminated from SN using random forest algorithm with a sensitivity Legal entity responsible for the study: The authors. of 1, specificity of 0.8, and AUC of 0.90 (95% CI, 0.77–1.00). To verify the Funding: Has not received any funding. accuracy, we performed 10-fold cross-validation, resulting in a mean Disclosure: F. Estevinho: Advisory/Consultancy: AstraZeneca; Advisory/ AUC of 0.933. Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Bristol-Myers Conclusions: Early stage LUAD manifested as radiological SSN has Squibb; Advisory/Consultancy: Novartis. All other authors have declared no conflicts of interest. increased microbiome richness and diversity compared with SN, and the April 2021 Abstracts S703

remunerated activity/ies, Non-financial support: Merck; Research grant/Funding 10P (self): Boehringer Ingelheim; Non-remunerated activity/ies, Non-financial support: Roche. All other authors have declared no conflicts of interest. Impact of the number of metastatic lymph nodes on survival in pathological stage II-N1 non-small cell lung cancer

J. de Ruiter1, A. de Langen2, K. Monkhorst3, A. Veenhof1, H. Klomp1, 11P R. Damhuis4, K. Hartemink1 1Surgery, NKI-AVL - Netherlands Cancer LINC00926 is a B cell-specific long non-coding RNA in lung Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands; adenocarcinoma and is associated with the prognosis of 2Thoracic Oncology, NKI-AVL - Netherlands Cancer Institute/Antoni van patients with this disease Leeuwenhoek Hospital, Amsterdam, Netherlands; 3Pathology, NKI-AVL - Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, J. Li1, H. Guo2,Y.Ma1, H. Chen3, M. Qiu1 1Thoracic Surgery, Peking Amsterdam, Netherlands; 4Research, Netherlands Comprehensive Cancer University People’s Hospital, Beijing, China; 2Beijing Chest Hospital, Organisation, Utrecht, Netherlands Beijing, China; 3Peking University People’s Hospital, Beijing, China

Background: Several single-centre studies investigated whether the Background: A previous report has shown that LINC00926 might be number of metastatic lymph nodes would be a relevant supplementary involved in the suppression of breast cancer metastasis. However, prognostic factor in pathological N1 (pN1) non-small cell lung cancer studies regarding the function of LINC00926 in lung adenocarcinoma (NSCLC), however, with conflicting results. The aim of this study was to are rare. determine the prognostic impact of the number of metastatic N1 lymph Methods: 10X single cell RNA sequencing (scRNA-seq) data of 8 healthy nodes in different histological subtypes for patients with stage II-N1 lung tissues and 5 lung adenocarcinoma tissues were obtained from NSCLC. our previous study. The sequence of LINC00926 was obtained from Methods: We performed a retrospective cohort study using data from Noncode (http://www.noncode.org/) and the cellular location of the the Netherlands Cancer Registry, including patients treated with a lncRNAs was predicted by lncLocator (http://www.csbio.sjtu.edu.cn/ surgical resection for stage II-N1 NSCLC in 2010–2016. Overall survival bioinf/lncLocator/). The target miRNA of the lncRNAs were predicted by (OS) was compared between patients with single (pN1a) versus Starbase (http://starbase.sysu.edu.cn/). The target genes of miRNAwere multiple (pN1b) metastatic pN1 nodes. With a multivariable analysis predicted by miRDB (http://mirdb.org/). Functional annotation of the we evaluated the impact of the number of metastatic pN1 nodes in target genes was made by DAVID (https://david.ncifcrf.gov/). The different histological subtypes. overall survival of patients in TCGA-LUAD with different expression level Results: The series involved 871 (67%) patients with pN1a and 438 of LINC00926 was compared by GEPIA (http://gepia.cancer-pku.cn/). (33%) with pN1b NSCLC. 5-year OS was 53% for pN1a versus 51% for Results: LINC00926 was specifically expressed in B cells in lung pN1b. 54.1% of patients with pN1a and 54.8% of patients with pN1b adenocarcinoma. However, LINC00926 was not expressed in B cells in received adjuvant chemotherapy. In multivariable analysis, the differ- normal lungs. LINC00926 was mainly located in the cytoplasm, ence between pN1b and pN1a was statistically significant, but small (HR suggesting that LINC00926 might function through RNA-sponge. 1.19, 95% CI 1.01–1.40). Furthermore, histological subtype, age, LINC00926 could bind the microRNA hsa-miR-3194-5p. The target pathological T stage, and adjuvant chemotherapy were independent genes of hsa-miR-3194-5p were enriched in Gene Ontology (GO) terms prognostic factors. When stratifying for histological subtype, the such as cell junction, protein kinase binding and Kyoto Encyclopedia of prognostic impact of pN1a/b was only observed in adenocarcinoma Genes and Genomes (KEGG) pathways such as Ras signaling pathway. patients (HR 1.44, 95% CI 1.15–1.81). Beneficial effects of adjuvant High expression of LINC00926 was associated with better overall chemotherapy were not different for pN1a versus pN1b. survival of patients with lung adenocarcinoma. Conclusions: The number of metastatic pN1 nodes was associated with Conclusions: LINC00926 might be a B-cell specific marker and might a minor difference in survival and its impact was limited to play a protective role in patients with lung adenocarcinoma. Further adenocarcinoma histology. Biological parameters such as histological research is needed to explore how LINC00926 functions in patients with subtype may be more appropriate for inclusion in future TNM revisions lung adenocarcinoma. and may guide the use of new (neo)adjuvant systemic therapies. Legal entity responsible for the study: Mantang Qiu. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest. Disclosure: A. de Langen: Research grant/Funding (self): BMS; Research grant/ Funding (self): MSD; Research grant/Funding (self): AstraZeneca; Non- ABSTRACTS

TRANSLATIONAL RESEARCH 13P M5C regulator-mediated methylation modification patterns 12P and tumour microenvironment infiltration characterization in Clonal evolution in lung cancer highlights MCL-1 gains as lung adenocarcinoma therapeutic target in lung adenocarcinoma H. Zhu1, M. Liu1,B.Xu2, H. Chen2, H. Cheng2, K. Zhao1 1Fudan 1 2 3 2 4 P.J. Jost , E. Munkhbaatar , M. Dietzen , C. Branca , N. McGranahan University Shanghai Cancer Center, Shanghai, China; 2The First Affiliated 1 2 Medical Oncology, Medical University of Graz, Graz, Austria; Medical Hospital of Nanjing Medical University, Nanjing, China Department 3, Technical University of Munich, Munich, Germany; 3Oncology, UCL - University College London, London, UK; 4Oncology, UCL Background: In recent years, immunotherapy has been greatly Cancer Institute - Paul O’Gorman Building, London, UK developed, and the regulatory role of epigenetics has been confirmed. However, the role of 5-methylcytosine (m5C) in tumor microenviron- Background: The analysis of recurrent genetic mutations in cancer ment and immunotherapy response is still unclear. driver genes represents a standard approach for patients diagnosed with Methods: Based on 11 m5C regulators, we evaluated m5C modification lung cancer. Yet, only about 15% of patients harbor activating mutations patterns of 572 lung adenocarcinoma patients. And m5C score was in oncogenic drivers that can be exploited therapeutically. Despite constructed by principal component analysis algorithms to quantify the substantial progress in immune check point inhibition, the survival data m5C modification pattern of individual lung adenocarcinoma patients. for a majority of mutation-negative patients remains unsatisfactory. Results: Two m5C methylation modification patterns were revealed Methods: Clonal evolution: Multi-region copy number data from the according to 11 m5C regulators. The two patterns had remarkably TRACERx study was used. The copy number values were adjusted by distinct tumor microenvironment (TME) immune cell infiltration ploidy and log-transformed. Gains with a copy number state >log2 (4/2) characterization. Then 226 differentially expressed genes related to were classified as high-level gains. Clonal gains were ubiquitously m5c phenotype were screened. Patients were divided into three different identified across every tumour region sequenced from a given tumour, gene cluster subtypes based on these genes, which had different TME while subclonal gains were identified as present in at least one tumour immune cell infiltration and prognosis characteristics. M5C score was region, but not all. To identify significant frequent gains and losses constructed to quantify the m5C modification pattern of individual lung across the cohort, the 95% quantile of the corresponding null adenocarcinoma patients. It can be seen that a high m5C score group had distribution was used as a threshold. A threshold of 20 Mb was used a better prognosis. The role of m5C score in predicting prognosis was to distinguish between focal and broad gains. In order to check which of also verified in GSE31210. the genes located in the gained area around MCL-1 show an increase in Conclusions: Our study revealed that m5C modification played a expression, the RNAseq data from the TRACERx cohort were analysed. significant role in TME regulation of lung adenocarcinoma. The study of The mRNA levels were measured as TPM (Transcripts Per Kilobase m5C regulation mode may have some implications for tumor immuno- Million) values. therapy in the future. Results: Here we show that an improved understanding of genetic Legal entity responsible for the study: The authors. liabilities beyond oncogenic driver alterations might improve patient Funding: Chinese Society of Clinical Oncology. outcomes. We provide evidence that non-oncogene addiction represents Disclosure: All authors have declared no conflicts of interest. a hallmark of lung cancer and the identification of such liabilities might provide an unprecedented treatment approach for lung cancer patients. The TRACERx data acquisition and analysis platform has provided a 14P variety of novel insights into lung cancer genetics, immune evasion and into the frequency and composition of chromosomal aberrations. We Studying tumour heterogeneity of primary non-small cell lung find that chromosomal gains range amongst the most common genomic cancer in humans and mice (PDX) events in lung cancer patients and their identification might represent a 1 1 2 3 3 viable option for drug targeting. Z. Kanaki , A. Voutsina , A. Markou , A. Markou , I. Samaras , 4 4 5 6 6 Conclusions: Overall, targeting genetic liabilities that serve as non- I.S. Pateras , E. Baliou , E. Patsea , K. Potaris , K. Vahlas , 6 7 1 4 oncogene addiction in lung cancer and that lie beyond oncogenic driver L. Toufektzian , I. Vamvakaris , P. Makrythanasis , V. Georgoulias , 8 1 1 alterations likely hold therapeutic promise. A. Kotsakis , A. Klinakis Biomedical Research Foundation, Academy of 2 Legal entity responsible for the study: The authors. Athens, Athens, Greece; ACTC Laboratory, Department of Chemistry, 3 Funding: German Cancer Aid. University of Athens, Athens, Greece; Department of Medical Oncology, 4 Disclosure: P.J. Jost: Honoraria (self), Advisory/Consultancy, Speaker Bureau/ University Hospital of Larissa, Larissa, Greece; Hellenic Oncology 5 Expert testimony, Research grant/Funding (institution), Travel/Accommodation/ Research Group (HORG), Athens, Greece; Department of Pathology, Expenses: Novartis; Honoraria (self), Research grant/Funding (institution): Metropolitan General Hospital, Athens, Greece; 6Department of Thoracic AbbVie; Honoraria (self), Travel/Accommodation/Expenses: Bayer; Honoraria Surgery, SOTIRIA General Hospital of Athens, Athens, Greece; 7Department (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Travel/Accommodation/Expenses: of Pathology, SOTIRIA General Hospital of Athens, Athens, Greece; 8 Servier; Honoraria (self), Speaker Bureau/Expert testimony, Travel/ Department of Medical Oncology, Faculty of Medicine, School of Health Accommodation/Expenses: Roche; Honoraria (self), Speaker Bureau/Expert Sciences, University of Thessaly, Larissa, Greece testimony, Travel/Accommodation/Expenses: BMS/Celgene; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer. Background: Tumor heterogeneity has been long considered to shape N. McGranahan: Honoraria (self), Shareholder/Stockholder/Stock options: tumor fitness and the metastatic potential of early stage tumor cells as Achilles Therapeutics. All other authors have declared no conflicts of interest. well as the therapeutic response in advanced stages. Methods: All primary tumors were implanted in immunocompromised NOD-SCID mice within 6 hours from surgery and passaged at least once before freezing. Both the primary tumor and the patient-derived xenograft were characterized with targeted exome sequencing against a panel of 70 genes which encompasses standard oncogenes and tumor suppressor genes involved in lung cancer, DNA damage/DNA repair proteins including those involved in homologous recombination, and

Journal of Thoracic Oncology Vol. 16 No. 4S: S704–S710 April 2021 Abstracts S705 others. Moreover, preoperative patients’ blood was analyzed for type. Studies are ongoing to explore the role epigenomic changes in the circulating tumor cells (CTCs) using the Parsortix platform and gene morphologically striking heterogeneity of PC. expression analysis. Legal entity responsible for the study: Luca Roma. Results: We surgically implanted more than 50 primary specimens from Funding: SNF Swiss National Science Fundation. patients with early stage operable NSCLC. Over 50% of those grafted Disclosure: All authors have declared no conflicts of interest. successfully. Our results indicate that the ability of primary tumors to successfully graft correlates significantly with tumor stage and grade, primary tumor size, and the detection of CTCs. Moreover, we observed 16P that squamous cell carcinomas are more likely to graft than adenocar- Prognostic role of circulating microRNAs involved in cinomas. Other than mutations associated tumor type (squamous vs. macrophage polarization in advanced non-small cell lung adeno), we did not observe any combination of mutations favors or disfavors grafting ability. The comparison between the genetic profile of cancer the primary tumor and the PDX revealed differences in some cases. 1 1 2 2 Detailed results will be presented. A. Monastirioti , C. Papadaki , K. Rounis , D. Kalapanida , D. Mavroudis2, S. Agelaki2 1School of Medicine, University of Crete, Conclusions: Primary early stage tumor samples from NSCLC patients 2 graft efficiently in immunocompromised mice while the grafting Heraklion, Greece; Department of Medical Oncology, University Hospital efficiency is affected by the tumoral clinic-pathological characteristics. of Heraklion (PAGNI), Heraklion, Greece Legal entity responsible for the study: The authors. Background: Circulating microRNAs (miRNAs) modulate immune Funding: AstraZeneca. response and the crosstalk between tumor cells and the immune Disclosure: All authors have declared no conflicts of interest. system. We herein investigated the association of miR-26a, let-7c, miR- 30d, miR-195, miR-202, miR-98, involved in the polarization of tumor associated macrophages (TAMs), with the outcome of non-small cell 15P lung cancer (NSCLC) patients (N = 125) treated with first-line platinum- The genomic landscape of pleomorphic lung cancer using based chemotherapy. whole exome sequencing Methods: MiRNA expression levels were analyzed by RT-qPCR in plasma obtained prior to the initiation of chemotherapy. U6 snRNA was L. Roma1, C. Ercan1, F. Conticelli2, S. Piscuoglio3,C.KyNg4, used as reference gene for normalization and fold change of each miRNA L. Bubendorf1 1Pathology Department, University Hospital Basel - expression relative to the expression in healthy controls was calculated −ΔΔCt Institute of Pathology, Basel, Switzerland; 2Department of Public Health, by the 2 method. University of Naples “Federico II”, Naples, Italy; 3Visceral Surgery and Results: High miR-202 expression was associated with disease Precision Medicine Research Laboratory, Department of Biomedicine, progression as best response to treatment (p = 0.030) and independ- University Hospital Basel - Institute of Pathology and Medical Genetics, ently predicted for both shorter progression free survival (PFS, p = Basel, Switzerland; 4Department for BioMedical Research (DBMR), 0.021) and overall survival (OS, p = 0.024), in the whole group of University of Bern, Bern, Switzerland patients. In the non-squamous (non-SqCC) subgroup, high miR-202 was also revealed as an independent predictor for shorter OS (p = 0.008). Background: Pleomorphic carcinoma (PC) is a rare subtype of non- High miR-26a was associated with a shorter OS in the SqCC subgroup small-cell lung cancer(NSCLC).PC is defined as highly heterogeneous and (p = 0.033). poorly differentiated adenocarcinoma, squamous cell carcinoma, or large Conclusions: These results suggest that the expression of circulating cell carcinoma containing at least 10% of sarcomatoid components of miRNAs involved in the regulation of TAMs, is associated with outcomes giant and/or spindle cells. PC has a more aggressive clinical course and a of patients with NSCLC treated with platinum-based chemotherapy. worse outcome than other NSCLCs. In comparison to pure LUAD and Further studies are required to clarify whether their role is prognostic or LUSC, it is not sufficiently characterized on a genomic and molecular level. predictive role and to establish their clinical validity. Understanding the molecularand genetic basis of PCs is necessary to find Legal entity responsible for the study: The authors. new treatment options. Here, we performed whole exome sequencing Funding: Hellenic Society of Medical Oncology (HESMO); Anticancer (WES) to investigate the genetic heterogeneity of this rare tumor type. Research Support Association (ARSA). Methods: FFPE (formalin-fixed, paraffin-embedded) sections were used Disclosure: All authors have declared no conflicts of interest. to dissect tumor tissue from six primary PCs (separate for each component) and from three matched metastases and were subjected to WES separately. 17P Results: The fourteen analyzed tumor areas including eleven areas from The value of Th2-related thymic stromal lymphopoietin as a six primary tumors and three matched metastases harbored a median of 334 (range 159–478) non-synonymous somatic mutations and a median prognostic and predictive biomarker in non-small cell lung of tumor mutation burden (TMB) of mutations/Mb 10,1 (range 4,8– cancer 14,5). KRAS and TP53 were the most frequently altered genes (4/6 1 2 3 2 1 patients), followed by FAT1 and KMT2D (3/6 patients). RBM10 was M. Cavic , V. Jokic , M. Marinkovic , N. Stanic , R. Jankovic , 2 2 1 mutated in 2/6 patients, followed by ALK, FBXW7, PIK3CA, ATM and D. Radosavljevic , J. Spasic Experimental Oncology Department, 2 MET altered in 1/6 patient. Furthermore, 3/6 patients showed Institute for Oncology and Radiology of Serbia, Belgrade, Serbia; Clinic concurrent mutations of KRAS and TP53. Clonality analysis showed for Medical Oncology, Institute for Oncology and Radiology of Serbia, 3 that most of cancer gene mutations found were clonal and truncal in Belgrade, Serbia; Clinic for Radiation Oncology and Diagnostics, both components of PCs. KRAS gene amplification was identified in 1/6 Department of Radiation Oncology, Institute for Oncology and Radiology patients with no simultaneous KRAS mutation. Mutational signature of Serbia, Belgrade, Serbia analysis showed that most of the mutations were dominated by ageing Background: The significance of the immune homeostasis modulator and smoking-related signatures number 1, 4 and 5. thymic stromal lymphopoietin (TSLP) in lung cancer has still not been Conclusions: The two different tumor components of PC are clonally explored in detail. The aim of this study was to assess the prognostic and related suggesting underlying transdifferentiation. The presence of the predictive potential of TSLP in EGFR-TKI treated non-small cell lung high frequency of the KRAS gene alterations including mutations and cancer. amplifications points to their primary role in the evolution of this tumor S706 Journal of Thoracic Oncology Vol. 16 No. 4S

Methods: The interactive publicly available database the Human Protein cases) for classifying samples into high or low expression. A combined Atlas was used to analyze the Cancer Genome Atlas (TCGA) transcrip- score with one point per positive marker was constructed. Multivariable tome data and assess the expression of TSLP in lung cancer. 101 Cox proportional hazards regression models were used to adjust for advanced EGFR mutated lung adenocarcinoma patients were treated stage, adjuvant treatment, smoking, age and gender. with TKIs until progression or unacceptable toxicity. Primary resistance Results: We identified 19 candidate markers and three were chosen for was defined as the absence of any response within the first 3 months of IHC validation; Ki67, MCM4 and TYMS. Protein expression of TYMS and therapy. Progression-free survival (PFS) was defined as the time from the Ki67 was significantly associated to OS while a trend towards worse start of therapy to date of clinical progression, and overall survival (OS) prognosis was seen in patients with high MCM4 expression. A high-risk as the time from diagnosis to death from any cause. TSLP gene group comprising patients positive for all three markers was identified. expression was determined by real-time qPCR. Receiver operating Conclusions: In summary, our gene expression-based strategy and characteristics analysis/area under the curve with 95% confidence subsequent IHC validation suggested three markers with prognostic interval was applied for the investigation of the discriminatory potential potential in AC. of TSLP expression (p < 0.05). Legal entity responsible for the study: Maria Planck. Results: In silico analysis showed that high TSLP expression is a favorable Funding: The Sjöberg Foundation, The Swedish Cancer Society, The prognostic factor in unselected lung adenocarcinoma patients with a 5- Kamprad Foundation. year survival rate for high expression of 51%, and 36% for patients with Disclosure: All authors have declared no conflicts of interest. low TSLP-expressing tumors (p = 0.0043, median follow up time: 1.79 years). However, in our study group of EGFR-TKI treated advanced lung adenocarcinoma patients, primary resistance was detected in 14 patients 19P and correlated with significantly higher pre-treatment levels of TSLP A synergistic combination therapy for KRAS-driven cancers compared to patients with disease stabilization and complete or partial response (1.04 ± 0.03 vs. 0.96 ± 0.04, p = 0.0001). Low TSLP expression Z. Yang, S-Q. Liang, R-W. Peng, R.A. Schmid Division of General predicted a favorable response to TKIs with a ROC cut-off value of 1.006 Thoracic Surgery, Department for BioMedical Research (DBMR), (AUC 0.713, 95% CI 0.569–0.831, p = 0.0015). Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland Conclusions: Increased levels of TSLP might lead to a switch to Th2- mediated immunity inducing a poor response to TKIs in advanced lung Background: KRAS is one of the most common oncoproteins in human adenocarcinoma. The combined effect of other Th2-related cytokines cancer but therapeutic strategies tailored to KRAS-mutant cancers has (IL-33, IL-25) on the response to TKIs is currently under investigation at remained an unmet medical need. One approach to treat KRAS-driven our Institute. tumors is to exploit collateral vulnerabilities or synthetic lethal partners Legal entity responsible for the study: The authors. that are essential in the context of oncogenic KRAS. PLK1 has been Funding: Ministry of Education and Science of the Republic of Serbia identified as a codependency in KRAS-mutant cancer cells as its (451–03-68/2020-14/200043). inhibition is synthetic lethal with KRAS mutations. However, PLK1 Disclosure: All authors have declared no conflicts of interest. inhibitors alone have only demonstrated limited efficacy in clinical studies, suggesting that additional targets are needed to improve PLK1- targeted therapy in KRAS-mutant cancers. 18P Methods: We performed chemical synthetic lethality screens to identify Gene expression-based identification of prognostic markers in complementary targets that enhance the efficacy of PLK1-targeted agents in KRAS-mutant cancer cells. Newly identified drug pairs were lung adenocarcinoma investigated in various tumor models of KRAS-mutant cancers. Results: Among others, we identified AZD4547 (FGFRs inhibitor) A. Salomonsson1,M.Jönsson1, H. Brunnström2, J. Staaf1, M. Planck1 synergizes with PLK1 inhibitors (BI2536/BI6727, a selective PLK1 1Department of Clinical Sciences, Division of Oncology, Lund University, inhibitor currently investigated in phase II/III clinical trials) to drive Lund, Sweden; 2Department of Clinical Sciences, Division of Pathology, KRAS-mutant cancer cell death. We provided evidence showing that Lund University, Lund, Sweden genetic and pharmacological inhibition of FGFR1 synergistically Background: By using high-throughput technologies many potentially enhances the effect of PLK1 inhibitors in KRAS-mutant lung and prognostic genes can rapidly be identified. However, new prognostic pancreatic cancer cells. Mechanistically, the combinatorial effect is markers must be validated in independent patient cohorts, add ascribed the surge of metabolic ROS and subsequently activation of JNK/ prognostic information to already existing tools and be assessed by a p38-dependent apoptosis. technique that is applicable in clinical laboratories. By using a Conclusions: Our results suggest a synergistic combination strategy for multicohort discovery and validation strategy we identified genes with the treatment of KRAS-mutant cancers. expression linked to overall survival (OS) in adenocarcinoma (AC) and Legal entity responsible for the study: The authors. subsequently validated candidate prognostic markers with immunohis- Funding: Has not received any funding. tochemistry (IHC). Disclosure: All authors have declared no conflicts of interest. Methods: Six publicly available gene expression datasets from microarray-based studies were used. In four discovery datasets the samples were, for each probe, dichotomized into two groups based on 20P the median gene expression values. The log-rank test was used to test for Synergistic inhibition of growth of KRAS-driven NSCLC by MEK differences in OS between the two groups and probes with p-value <0.05 inhibitor in combination with a novel multi-target tyrosine were collected for each dataset. Only probes with p-value <0.05 in all kinase inhibitor anlotinib via IGFBP-mediated signaling four datasets could proceed to the validation step where the probes were tested as above in two additional gene expression datasets. Probes with M. Hu, J. Lu, B. Han Pulmonary Department, Shanghai Chest Hospital p-value <0.05 in both validation datasets were considered as candidate Affiliated to Shanghai Jiao Tong University, Shanghai, China markers and three of these were selected for IHC validation. IHC stainings were performed on tissue microarrays. A cohort consisting of Background: Kirsten rat sarcoma viral oncogene (KRAS) mutations 124 surgically treated AC cases was used as a discovery cohort. By using occur frequently in NSCLC (non-small cell lung cancer), but clinically Kaplan-Meier plots with log-rank test we identified preliminary cut-offs applicable targeted therapy is limited until now. This study set out to (currently being validated in an independent cohort comprising 131 AC evaluate a novel strategy to treat KRAS-driven lung cancer. April 2021 Abstracts S707

Methods: The in vitro effects of the combined use of anlotinib and trametinib were evaluated by cell viability assay, wound healing scratch 22P assay, clonogenic survival assay and flow cytometry. A xenograft model Clinical utility of ddPCR for detection of sensitizing and was used to evaluate the inhibitory effect of the drug combination on resistance EGFRm in pts with advanced NSCLC KRAS-driven NSCLC growth in vivo. The transcriptome-wide differential gene expression analysis and protein microarray were applied to M. Riudavets1, V. Lamberts1, E. Auclin2, M. Aldea1, D. Vasseur3, discover underlying molecular mechanisms. C. Jovelet3, C. Naltet1, P. Lavaud1, A. Gazzah1, F. Aboubakar1, Results: Anlotinib was found to synergize with trametinib in vitro and in J. Remon1, E. Rouleau3, L. Lacroix3, M. Ngocamus4, C. Nicotra4, vivo to further exert anti-tumor effects on KRAS-mutant lung cancer. B. Besse1, D. Planchard1, L. Mezquita5 1Dept. Medical Oncology, Furthermore, we reported that the expression of IGFBP2 decreased Institut Gustave Roussy, Villejuif, France; 2Dept. Medical Oncology, Hôpital significantly in the dual-drug group, which was a key protein that mediated Europeeń Georges Pompidou, Paris, France; 3Dept. Molecular Biology, the synergistic effect by regulating the cell cycle and EMT process. Institut Gustave Roussy, Villejuif, France; 4Dept. Early Drug Development, Recombinant IGFBP2 protein could restore the inhibitory effects of dual Institut Gustave Roussy, Villejuif, France; 5Dept. Medical Oncology, drugs on KRAS-mutant tumor proliferation, invasion and migration. Hospital Clinic i Provincial de Barcelona, Barcelona, Spain Conclusions: Overall, the findings of this research provide insights for clinical application of anlotinib and trametinib in treating KRAS-driven Background: EGFR mutations (EGFRm) represent 10–15% of advanced NSCLC. non-small cell lung cancer (NSCLC) in European patients (pts). Tissue Legal entity responsible for the study: The authors. molecular profiling is the gold-standard, but liquid biopsy (LB) offers a Funding: Has not received any funding. non-invasive alternative. Digital droplet PCR (ddPCR) is a fast, high- Disclosure: All authors have declared no conflicts of interest. sensitive and low-cost LB to detect specific molecular alterations. We aimed to describe ddPCR clinical utility for EGFRm detection in advanced NSCLC. 21P Methods: Prospective blood sample collection in advanced NSCLC pts The landscape of ALK alterations in non-small cell lung cancer harboring EGFRm either at baseline and/or at progression (PD) between Jan/16 and Sep/20 at Gustave Roussy. LB was performed by ddPCR (Stilla®): sensitizing (exon19 deletion; exon21 [L858R]) and T790M A. Desai1, T. Mohammed2, S. Rakshit1, J. Krull1 1Oncology, Mayo Clinic, resistance EGFRm. We defined high tumor burden as >2 metastatic sites. Rochester, MN, USA; 2University of Connecticut, Hartford, CT, USA We analyzed EGFRm detection by ddPCR at these timepoints. Background: Aberrant expression of Anaplastic lymphoma kinase Results: A total of 252 samples were collected (N = 140 pts): 27 at (ALK) has been recognized as potent drivers of oncogenesis in non-small baseline, 144 at PD and 81 under response. Median of samples/pts was 1 cell lung cancer (NSCLC). Detecting ALK gene rearrangements in [1–8]. Median age was 66 [36–92]; 29% were female, 62% non-smokers patients with newly diagnosed NSCLC is critical, as the presence of and 97% had adenocarcinoma histology. At baseline, sensitizing EGFRm this oncogene influences treatment opportunities. Given the recent were detected in 59% (16/27) of samples: 12 ex19del and 4 ex21. approval of multiple drugs targeting ALK-rearranged NSCLC, optimal Median number of sites was 3 [1–5]. In pts with intracranial and/or first-line therapy is an area of active debate. The recently published thoracic isolated lesions, EGFRm were detected in 33% (2/6); in those CROWN trial showed that lorlatinib retains potency against all known with high tumor burden detection was 78% (7/9). At PD, sensitizing single ALK resistance mutations, including ALK G1202R. Here, we EGFRm were detected in 57% (82/144) of samples: 64 ex19del and 18 present a comprehensive analysis of ALK alterations in NSCLC. ex21. Median number of PD sites was 3 [1–8]; lung (70%) and bone Methods: Patient-specific ALK alterations were analyzed using the (64%) were the most common. In pts with intracranial/thoracic isolated open-source AACR Project GENIE Cohort v8.1. Using cbioportal as a lesions, EGFRm were detected in 31% (11/35); in those with high tumor query database, we analyzed 11,107 samples from 10,082 patients of burden detection was 67% (54/81). At PD to 1st–2nd generation lung adenocarcinoma for the prevalence of ALK fusions, mutations, and tyrosine-kinase inhibitors, sensitizing EGFRm were detected in 49% copy number alterations in NSCLC. (40/81) of samples. The T790M mutation was found in 22% (18/81) Results: 584 (5% of queried samples) ALK alterations were detected, overall, all of them with positive ddPCR sensitizing EGFRm (45%, 18/ including 354 missense mutations (60.6%), 265 fusions (45.4%), 51 40); detection rate was 9% (2/23) for intracranial/thoracic vs. 32% (13/ truncating mutations (8.7%), and 1 in-frame mutation (0.17%). 41) for high tumor burden cases. Following the exclusion of alterations with mutations and copy Conclusions: ddPCR is a sensitive liquid biopsy for sensitizing and number alterations of unknown significance, 284 (2%) of samples still resistance EGFRm detection. ddPCR positivity was more likely observed had significant ALK alterations. Among them, there were 259 fusions and in systemic PD cases with high tumor burden. It can provide a rapid 25 missenses mutations identified. Of the 25 missense mutations, we EGFRm result to guide treatment in NSCLC, however metastatic profile identified only 7/284 (2.46%) mutations with G1202R protein change, should be taken into account. 7/284 (2.46%) mutations with L1196M, and 4/284 with I1171N which Legal entity responsible for the study: The authors. were all identified as oncogenic. The most common ALK gene upstream Funding: Has not received any funding. partners were EML4, KIF5B, and SQSTM1 (81.5%, 1.5%, and 1.1%) of Disclosure: C. Naltet: Advisory/Consultancy: Roche; Advisory/Consultancy: identified ALK fusions, respectively. ALK fusions were significantly co- Bristol-Myers Squibb; Advisory/Consultancy: AstraZeneca; Advisory/ Consultancy: Pfizer. P. Lavaud: Travel/Accommodation/Expenses: Ipsen; Travel/ altered with HSP90AB1 mutations (p = 2.51E-04), IDH2 mutations (p = Accommodation/Expenses: Astellas; Travel/Accommodation/Expenses: Janssen; 0.027), and NRG1 mutations (p = 0.024). Travel/Accommodation/Expenses: Mundi Pharma; Honoraria (self): AstraZeneca. Conclusions: Most ALK variants are described as VUS, limiting the A. Gazzah: Research grant/Funding (self), Travel/Accommodation/Expenses: impact of precision oncology. ALK fusions occur in 2.6%% of the lung Boehringer Ingelheim; Speaker Bureau/Expert testimony, Research grant/ Funding (self), Travel/Accommodation/Expenses: Novartis; Research grant/ adenocarcinomas, with EML4 being the most common upstream partner. Funding (self), Travel/Accommodation/Expenses: Pfizer; Research grant/ Meanwhile, G1202R mutations occur only among 0.07% of the ALK Funding (self), Travel/Accommodation/Expenses: Roche; Research grant/ alterations. Heat shock protein and Neuregulin-1 pathway may present Funding (self): AstraZeneca; Research grant/Funding (self): Sanofi; Research additional opportunities for combination targeted therapies in the grant/Funding (self): Janssen; Research grant/Funding (self): Merck; Research grant/Funding (self): Bristol-Myers Squibb. L. Lacroix: Advisory/Consultancy: future for ALK-positive NSCLC. Abott; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Boehringer Legal entity responsible for the study: The authors. Ingelheim; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Funding: Has not received any funding. Bayer; Advisory/Consultancy: Illumina; Advisory/Consultancy: Genomic Health; Disclosure: All authors have declared no conflicts of interest. Advisory/Consultancy: Myriad; Advisory/Consultancy: Novartis; Advisory/ S708 Journal of Thoracic Oncology Vol. 16 No. 4S

Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Conclusions: Pleural lavage fluid cfDNA identification is a feasible Siemens; Advisory/Consultancy: Thermofisher; Advisory/Consultancy: VelaDx. method in resectable NSCLC patients. Median cfDNA values decrease B. Besse: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research after one month of surgery. Although PLV cytology was negative, cfDNA grant/Funding (institution): Biogen; Research grant/Funding (institution): in PLV correlates positively with PrePL cfDNA levels in resectable NSCLC. Blueprint Medicines; Research grant/Funding (institution): Bristol-Myers Also, higher cfDNA in PLV predicts more towards early recurrences than Squibb; Research grant/Funding (institution): Celgene; Research grant/Funding plasma cfDNA labels even when they were at distant sites. (institution): Eli Lilly; Research grant/Funding (institution): GKS; Research grant/ Funding (institution): Ignyta; Research grant/Funding (institution): Ipsen; Legal entity responsible for the study: The authors. Research grant/Funding (institution): Merck KGaA; Research grant/Funding Funding: Has not received any funding. (institution): MSD; Research grant/Funding (institution): Nektar; Research Disclosure: All authors have declared no conflicts of interest. grant/Funding (institution): Onxeo; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Pharma Mar; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Spectrum Pharmaceuticals; Research grant/Funding (institution): Takeda; Research grant/ 24P Funding (institution): Tiziana Pharma. D. Planchard: Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Peripheral blood transcriptomics reveal novel resistance Honoraria (institution), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria mechanisms in immune checkpoint inhibitor (ICI) treated (institution), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (institu- non-small cell lung cancer (NSCLC) patients tion), Advisory/Consultancy: Celgene; Advisory/Consultancy: Daiichi Sankyo; Honoraria (institution), Advisory/Consultancy: Eli Lilly; Honoraria (institution), Advisory/Consultancy: Merck; Honoraria (institution), Advisory/Consultancy, J. Mankor, H. Vroman, R. Stadhouders, A-M.C. Dingemans, J.G. Aerts Travel/Accommodation/Expenses: Novartis; Honoraria (institution), Advisory/ Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (institution), Netherlands Advisory/Consultancy, Travel/Accommodation/Expenses: prIME Oncology; Honoraria (institution), Advisory/Consultancy: Peer CME; Honoraria (institution), Background: Previous studies have demonstrated that peripheral blood Advisory/Consultancy, Travel/Accommodation/Expenses: Roche. L. Mezquita: + Research grant/Funding (self): Amgen; Honoraria (self), Research grant/ PD-1 CD8 T cells are important determinants of NSCLC immune Funding (self), Travel/Accommodation/Expenses: Bristol-Myers Squibb; checkpoint inhibitor (ICI) efficacy. This subset likely comprises tumor- Research grant/Funding (self): Boehringer Ingelheim; Honoraria (self), specific cytotoxic T cells. However, little is known about the phenotype of Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/ these cells. To address this question, we isolated RNA from peripheral Consultancy: Takeda; Honoraria (self): Technofarma; Leadership role: + AstraZeneca. All other authors have declared no conflicts of interest. blood mononuclear cells (PBMCs) PD-1 CD8 T cells of patients with NSCLC who were treated with ICI, aiming to map the transcriptomic landscape in relation to ICI response. Methods: We collected PBMCs of patients with stage IV NSCLC prior to 23P the first (n = 12) and third cycle of nivolumab (n = 9). We sorted PD-1+ Clinical utility of cell free DNA in pleural lavage and plasma in CD8 T cells, isolated RNA and sequenced cDNA libraries (Illumina resectable NSCLC: A pilot study HiSeq2500). After alignment, we performed differentially expressed gene analyses using DESeq2. Efficacy of treatment was assessed 1 2 1 1 1 2 J. Saikia , P. Malik , D. Jain , S. Kumar , S. Bharati , K. Madan , according to Response Evaluation Criteria in Solid Tumors v.1.1. 1 1 1 1 P. Gamit , S.V.S. Deo , S. Kumar Surgical Oncology, All India Institute Results: In this cohort, 7 patients acquired durable clinical benefit, 2 of Medical Sciences, New Delhi, India; All India Institute of Medical defined as progression-free survival (PFS) of 6 months or longer and are Sciences, New Delhi, India referred to as responders (R). The remaining 5 patients are referred to as Background: Cell free DNA has been found in pleural effusion in non-responders (NR). Unsupervised hierarchical clustering revealed a patients with pleural metastases. But the role of cfDNA in pleural lavage cluster of interferon-related genes (OASL, IFIT2, IFIT3, GPAT3, CD200R) in resectable primary NSCLC is unknown. We aimed to find out the that was significantly upregulated in NR pre-treatment. Pre-treatment feasibility of identification of cfDNA in pleural lavage fluid and its IFIT2 and IFIT3 gene expression was significantly correlated to PFS 2 2 correlation with plasma in resectable NSCLCs. (IFIT 2 R = 0.50, p = 0.01, IFIT3 R = 0.40, p = 0.03). Methods: We evaluated the intraoperative cfDNA levels in pleural lavage Conclusions: Using in-depth transcriptomic analysis, we identified a (PLV) and plasma (PrePL) in all consecutive resectable NSCLCs patients subset of interferon-related genes upregulated in NR patients prior to pre-resection in the last 3 years. Another paired blood sample (PostPL) aPD-1 treatment. Interestingly, interferon-induced proteins with tetra- was collected at 1 month after surgery. Cell-free DNA was isolated from tricopeptide repeats (IFIT proteins) are upregulated upon T cell receptor + the stored pleural lavage and plasma using QIAamp DNA Blood Mini Kit stimulation. Thus, upregulation of IFIT genes could indicate that PD-1 (QIAGEN). The extracted plasma and pleural lavage DNA was measured CD8 T cells experienced prolonged tumor antigen stimulation, inducing quantitatively by qPCR in a TaqMan probe detection approach using an exhausted state and rendering them insensitive to aPD-1. This + human β-actin gene as the amplifying target. A part of the same PLV fluid analysis not only reveals novel characteristics of circulating PD-1 CD8 T was also examined for malignant cytology. cells but also provides a promising lead for developing accessible pre- Results: Only 29 patients were found suitable. The median cfDNA levels treatment ICI resistance markers. in PrePL, PostPL and PLV were 158.5ngldl, 112.5 ng/dl and 197.5 ng/dl Legal entity responsible for the study: Erasmus Medical Center, respectively. At a follow up of 2 years there is a trend towards significant Rotterdam. decrease in disease free survival (p = 0.07) with pleural lavage cfDNA Funding: Has not received any funding. levels more than 185 ng/ml. A positive correlation was found between Disclosure: A-M.C. Dingemans: Honoraria (institution): Roche; Honoraria (institution): Pfizer; Honoraria (institution): Boehringer Ingelheim; Honoraria preoperative plasma levels and pleural lavage levels of cfDNA. There was (institution): Eli Lilly; Honoraria (institution): Takeda; Honoraria (institution): no significant differences in cfDNA levels in pleural lavage or plasma Amgen; Honoraria (institution): BMS; Honoraria (institution): Novartis. J.G. Aerts: with respect to age, sex, smoking or TNM stages. For T stage upto 5 cm Honoraria (institution), Advisory/Consultancy: Eli Lilly; Honoraria (institution), median cfDNA levels were higher than those more than 5 cm. There is Advisory/Consultancy: Roche; Honoraria (institution), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy: BMS; trend towards significantly higher values when the cutoff for plasma Honoraria (institution), Advisory/Consultancy: MSD; Honoraria (institution), cfDNA before surgery was kept at 160 ng/dl (p = 0.06). A trend towards Advisory/Consultancy, Shareholder/Stockholder/Stock options: Amphera B.V.; significant recurrences when the PrePL is more than 125 ng/dl (p = Honoraria (institution), Advisory/Consultancy: AstraZeneca. All other authors 0.087). PLV cytology for malignant cells was negative in all. have declared no conflicts of interest. April 2021 Abstracts S709

understand the molecular profile of tumors and thus, the identification 25P of possible biomarkers related to prognosis and response. Evaluation of PD-L1 and Ki67 markers in CTCs of NSCLC Methods: In our study, we proposed the analysis of a cohort of 13 patients treated with pembrolizumab patients with squamous histology but different topographic locations (7 with lung cancer, 1 with bladder cancer, 1 with cervical cancer, and 1 M. Spiliotaki1, H. Charalambous2, C.M. Neophytou1, G. Gregoriou1, with head and neck cancer and 2 of origin unknown). The samples were P. Vogazianos3, C. Deltas4, A.I. Constantinou1 1Biological Sciences, analyzed by NGS with the OncoDEEP (OncoDNA) panel covering 313 University of Cyprus, Nicosia, Cyprus; 2Bank of Cyprus Oncology Centre, genes. Nicosia, Cyprus; 3European University of Cyprus, Nicosia, Cyprus; 4Medical Results: Only one of the cases was not evaluable due to the low Sciences, University of Cyprus, Nicosia, Cyprus cellularity of the tumor block. Of the 12 evaluable cases, molecular alterations were identified in 6 of them, as detailed below: in case Background: Tumor Programmed cell death protein ligand-1 (PD-L1) number 1 (lung cancer) variant of TP53 cDNA c.595G> T-AA p. G199, in expression is used to guide treatment of Non-Small Cell Lung Cancer case number 2 (lung cancer) mutation in TP53 cDNA c.488a> G-AAp. (NSCLC) patients with Pembrolizumab. PD-L1 expression on circulating Y163C and mutation in FANCA cDNA: c.3263C> T-AA: p.S1088F, in case tumor cells (CTCs) may provide further predictive information. number 3 (lung cancer) variant de TP53 c.DNA: c.455del-Aap.P152Rfs * Methods: In a prospective maintenance study of Pembrolizumab in 18, alteration in MRE11A cDNA: c.1688C> G-AA: p.S563 * and alteration NSCLC patients (NCT02705820), we evaluated the predictive role of KEAP1 cDNAc.224dup-Aap.L76Afs * 3, in case number 4 (lung cancer) CTCs expressing PD-L1 and Ki67 (n = 48). A triple immunofluorescence AKT amplification and alteration in BRCA2 cDNA c.2701del-Aap. assay against cytokeratin (CK), PD-L1 and Ki67 was performed in A902Lfs * 2, in case number 5 (lung cancer) mutation in PI3KCA peripheral blood mononuclear cell cytospins prior and after first cycle. E545 K, amplification in MDM2 and mutation in TP53 cDNA c.871AA> PD-L1 levels on CTCs were classified as PD-L1- PD-L1low, PD-L1med and T-AA p.K291 *, in case number 6 (bladder cancer) amplification of JAK1 PD-L1high. CK+CTCs were also classified as Ki67+ or Ki67−. and in case number 7 (head and neck cancer) mutation of PI3KCA E545, Results: Among 45 CTC+ patients, 14 had a durable clinical benefit mutation of TPMT Y240C and mutation in TPMT A154 T. (DCB) (PFS lasting>12 months) whereas 31 showed no durable benefit Conclusions: This review presents as its objective the analysis of these (NDB). Patients with at least one PD-L1high CTC 79% (19/24) and molecular alterations and their impact on the prognosis, and therapeutic patients with PD-L1- CTCs 79% (11/14) were more often encountered evolution of patients with the aim of integrating clinical and molecular in NDB, while patients harbouring only PD-L1med and/ or PD-L1low CTCs information in a translational oncology study. 86% (6/7) were more often found in DCB (79%, 79%, 14% in NDB vs Legal entity responsible for the study: The authors. 21%, 21%, 86% in DCB p = 0.003). A higher percentage of patients with Funding: Has not received any funding. Ki67+ CTCs showed NDB 81% (22/27) compared to those not Disclosure: All authors have declared no conflicts of interest. presenting 50% (9/18) p = 0.02. Regarding the co-expression of both markers the PD-L1high/Ki67+ phenotype prevailed in NDB 89% (17/19) compared to patients not having this 54% (14/26) p = 0.01. In contrast, 27P med − patients with PD-L1 /Ki67 CTCs >20% more often showed DCB The association between gut microbiome and response to 60% (6/10) compared to those not presenting 23% (8/33) p = 0.01. high checkpoint inhibitor therapy in non-small cell lung cancer Interestingly, PD-L1 /Ki67+ CTCs (thresholds ≥1% and >20%) were related to shorter overall survival (OS) (p = 0.036 and p = 0.030) while 1 2 1 med J. Moon , H. Moon Emergency Medicine, Sungju Moogang Hospital, PD-L1 /Ki67− CTCs (threshold >20%) were related to increased OS Sungju, Republic of Korea; 2Obstetrics and Gynaecology, Severance (p = 0.036). After first cycle, a significant reduction in the average % of med Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea the PD-L1 /Ki67− CTCs per patient from 26% to 10%, was observed in patients with DCB (p = 0.043). Background: The diversity and composition of gut microbiome plays a Conclusions: A differential distribution of the PD-L1 and Ki67 crucial role in the host immune response. As such, the gut microbiome phenotypes was observed in patients with different clinical benefit has been implicated in the pathophysiology of many seemingly unrelated during Pembrolizumab treatment. CTC characterization according to PD- diseases. With regards to non-small cell lung cancer (NSCLC), it has been L1 and Ki67 may provide valuable biomarkers to monitor NSCLC shown in multiple studies that antibiotic treatment attenuates the patients treated with Pembrolizumab. outcome of immune checkpoint inhibitor (ICI) therapy and also that ICI Legal entity responsible for the study: The authors. therapy leads to alterations in the gut microbiome profile. Therefore, the Funding: The Cyprus Research and Innovation Foundation. objective of this review was to analyze available data on the relationship Disclosure: All authors have declared no conflicts of interest. between gut microbiome and response to ICI therapy in NSCLC patients. Methods: Two independent investigators reviewed the PubMed, Google Scholar, and Embase databases. Studies that utilized a metabolomics 26P profiling approach were excluded to maintain consistency in data Analysis of prognostic and predictive factors of response in collection and analysis. squamous cell carcinoma using NGS techniques Results: A total of four studies published in 2019 and 2020 met our inclusion criteria and were included in this review. Two studies were P. Cruz Castellanos1, L. Gutierrez Sainz1, O. Higuera Gomez1, from China and the other two were from Japan. The patients included in C. Antolin2, R. Rosas Alonso2, I. Ibañez2, B. Castelo1, these studies were all diagnosed with advanced NSCLC and underwent X. Mielgo Rubio3, J. De Castro Carpeno1 1Medical Oncology treatment with anti-PD-1 inhibitors. Assessment of gut microbiota Department, Hospital Universitario La Paz, Madrid, Spain; 2Experimental profiles was carried out using 16S ribosome RNA gene sequencing. All Therapies and Novel Biomarkers in Cancer, Hospital Universitario La Paz, studies had similar results, with higher microbiome diversity being Madrid, Spain; 3Medical Oncology Department, Hospital Universitario associated with longer progression-free survival periods. Patients who Fundacioń Alcorcon,́ Alcorcon, Spain were pre-treated with antibiotics were found to have lower diversity and an underrepresentation of bacterial species that were associated with a Background: In recent years, the diagnosis and treatment of different favorable outcome. The specific compositional differences observed in neoplasms has undergone a great change due to the development of the studies varied greatly; patients with more favorable outcome had a immunotherapy and targeted therapies. Furthermore, the incorporation greater representation of such bacterial species as Parabacteroides, of massive sequencing techniques (NGS) has made it possible to better S710 Journal of Thoracic Oncology Vol. 16 No. 4S

Methanobrevibacter, Lactobacillus, Clostridium, Agathobacter, and (n = 86/109). In 78% (n = 85/109) of patients, the treatment recom- Bifidobacterium longum. mendations from the multidisciplinary tumor boards were completely Conclusions: NSCLC patients with more favorable outcome after ICI adhered to. There were different reasons for non-adherence, e.g. therapy were associated with a higher microbiome diversity and patient’s wish, patient characteristics and death before starting exhibited specific compositional differences. Futher studies are war- therapy. The median overall survival for the 109 patients was 109 ranted to determine how to modulate the gut microbiome to maximize months. Patients with a complete adherence to the multidisciplinary outcomes in NSCLC patients undergoing ICI therapy. tumor board recommendation had an overall survival of 17 months (n = Legal entity responsible for the study: The authors. 84) compared to 7 months (n = 13) for patients with a partial adherence Funding: Has not received any funding. compared to 1 months (n = 11) for patients with a non-adherent Disclosure: All authors have declared no conflicts of interest. treatment (p < 0.000). Conclusions: Preliminary results give a hint to the fact that patients with an adherent treatment after first diagnosis had a longer overall survival 28P than patients with another therapy. More cases will be presented at the Adherence to treatment recommendations from meeting using a multivariate analysis which includes patient characteristics and healthcare organizations that took over further treatment as multidisciplinary tumour boards predictors. Legal entity responsible for the study: University Hospital Internal J. Roeper1, L. Kathmann1, A. Blanksma1, L. Ansmann2, F. Griesinger1 Medicine-Oncology, Pius Hospital Oldenburg, University Oldenburg. 1Department of Internal Medicine-Oncology, Pius Hospital, Oldenburg, Funding: Has not received any funding. Germany; 2Department of Health Research, University of Oldenburg, Disclosure: J. Roeper: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Oldenburg, Germany AstraZeneca; Honoraria (self): Roche. F. Griesinger: Honoraria (self), Advisory/ Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institu- Background: Due to the German National Cancer Plan, cancer centers tion), Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), have been established. Lung cancer centers are responsible for Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ coordinating the care of lung cancer pts in a region and to diagnose Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria and treat them according to the latest evidence-based knowledge. For (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), this purpose, every patient should be discussed in a multidisciplinary Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ tumor board. In the tumor board an individual treatment plan is Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria discussed and treatment recommendations are given. Therefore, we (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ investigate: 1.) how are the recommendations from tumor boards being Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ adhered to; 2.) which factors determine the adherence of tumor board Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), recommendations and 3.) what is the relationship between the Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ adherence of tumor board recommendations and patient outcomes in Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), terms of overall survival?. Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ Funding (institution), Travel/Accommodation/Expenses: Siemens; Honoraria Methods: Data from 1784 newly-diagnosed pts with lung cancer (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ discussed in tumor boards in one certified lung cancer center in Funding (institution), Travel/Accommodation/Expenses: Celgene; Honoraria Northern Germany between 2014 and 2018 were documented and (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ evaluated according to the adherence to tumor board recommendations. Funding (institution), Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ A preliminary analysis of the first 109 cases analyzed will be presented. Funding (institution), Travel/Accommodation/Expenses: Takeda; Honoraria Results: Median age of the 109 pts was 67 years (36–88 yrs) and 59% (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ (n = 64/109) of them were male. Most of the pts had an ECOG of 0 or 1 Funding (institution), Shareholder/Stockholder/Stock options: AbbVie. All other (71%; n = 77/109) and 79% of them were current or ex heavy smoker authors have declared no conflicts of interest. ABSTRACTS

Clinical trial identification: NCT04419207. PREVENTION, EARLY DETECTION, Legal entity responsible for the study: Mantang Qiu and Zuli Zhou. EPIDEMIOLOGY, TOBACCO CONTROL Funding: The National Natural Science Foundation of China. Disclosure: All authors have declared no conflicts of interest.

29MO 30P Early-stage lung cancer detection by a noninvasive breath test Trends and variations in treatment of stage I-III non-small cell – M. Qiu1, Z. Zhou1, S. Meng1,H.Li2,Q.Li2, J. Wang1 1Thoracic Surgery, lung cancer from 2008 2018: A nationwide population-based Peking University People’s Hospital, Beijing, China; 2Shenzhen Breatha study from the Netherlands Biological Technology Co., Ltd, Shenzhen, China J. Evers1, K. De Jaeger2, L. Hendriks3, M. Van der Sangen2, Background: Breath analyses of volatile organic compounds in exhaled C. Terhaard4, S. Siesling1, D. De Ruysscher5, H. Struikmans6, breath is a promising option for cancer detection. To establish a feasible M.J. Aarts1 1Research and Development, Netherlands Comprehensive and noninvasive detecting method of lung cancer, we have made Cancer Organisation (IKNL), Utrecht, Netherlands; 2Department of substatial improvement to the highly sensitive high-pressure photon Radiation Oncology, Catharina Hospital, Eindhoven, Netherlands; ionization time-of-flight mass spectrometry (HPPI-TOFMS). In this study, 3Department of Pulmonary Diseases, Maastricht University Medical we investigated the accuracy of a breath test using HPPI-TOFMS to detect Center, GROW School for Oncology and Developmental Biology, lung cancer from healthy controls. Maastricht, Netherlands; 4Department of Radiation Oncology, Utrecht Methods: 1000 ml exhaled breath was collected from each participant University Medical Center, Utrecht, Netherlands; 5Department of with air bags. A CO2 sensor was applicated during sample collection to Radiation Oncology (MAASTRO Clinic), Maastricht University Medical ensure “alveolar air” was collected. Exhaled breath samples were Center, GROW School for Oncology and Developmental Biology, detected by HPPI-TOFMS. Detection model construction was performed Maastricht, Netherlands; 6Department of Radiation Oncology, Leiden by support vector machine (SVM) algorithm. University Medical Centre, Leiden, Netherlands Results: In total, 139 lung cancer patients and 289 healthy controls were eligible and included in this study. Most lung cancer patients were at Background: This Dutch population-based study describes not early stage (TNM stage I-II, 126/139). All exhaled breath samples were previously well-documented nationwide treatment patterns and its prospectively collected and tested. After clinical outcomes were variations for stage I–III non-small cell lung cancer (NSCLC). ascertained, all participants were randomly assigned into the discovery Methods: Patients diagnosed with clinical stage I–III NSCLC in the cohort (n = 381) and the blinded validation cohort (n = 47). The period 2008–2018 were selected from the Netherlands Cancer Registry. discovery cohort was further broken into a training set (n = 286) and Treatment trends were studied over time and age groups. Use of a test set (n = 95) to construct and test the detection model. SVM built a radiotherapy versus surgery (stage I–II), and concurrent (cCRT) versus detection model that accurately distinguished lung cancer patients from sequential chemoradiotherapy (sCRT) (stage III) were analyzed by controls in the training set. The detection model reached 92.97 ± logistic regression. 0.046% sensitivity, 96.68 ± 0.022% specificity, and 95.51 ± 1.93% Results: In stage I, the rate of surgery decreased from 58% (2008) to accuracy in the test set after 500 times iterations, which was termed 40% (2018), while radiotherapy use increased over time (from 31% to as “BreLC v1.0”. Finally, in the blinded validation cohort (n = 47), BreLC 52%). In stage II, 54% of patients received surgery, and use of revealed a sensitivity of 100%, a specificity of 92.86%, an accuracy of radiotherapy alone increased from 18% to 25%. The strongest factors 95.74%, and an AUC of 0.9586. favoring radiotherapy over surgery were WHO performance status (OR ≥2 vs 0: 23.39 (95%CI: 18.93–28.90)), increasing age (OR ≥80 vs <60 yr: 14.52 (95%CI: 13.02–16.18)) and stage (OR stage II vs I: 0.61 Table 29MO: Baseline characteristics of enrolled participants (95%CI: 0.57–0.65)). In stage III, the combined use of chemotherapy and Discovery Cohort Validation Cohort radiotherapy increased from 35% (2008) to 39% (2018). In all years, 23% received cCRT, 9% sCRT, 23% radiotherapy or chemotherapy alone, Lung Healthy Lung Healthy and 25% best supportive care. The strongest factors favoring cCRT over cancer control P cancer control P sCRT were age (OR ≥80 vs <60: 0.14 (95%CI: 0.10–0.19)), WHO Sex 0.070 0.160 Performance status (OR ≥2 vs 0: 0.33 (95%CI: 0.24–0.47)) and region Male 46 (38.3%) 126 (48.3%) 9 (47.4%) 19 (67.9%) (OR east vs north: 0.39 (95%CI: 0.30–0.50)). Female 74 (61.7%) 135 (51.7%) 10 (52.6%) 9 (32.1%) Conclusions: The use of radiotherapy became more prominent over Age 60.4±10.5 55.7±12.1 <0.001 58.3±8.5 53.9±8.1 0.670 time in stage I NSCLC. Combined use of chemotherapy and radiotherapy Smoking 0.963 0.188 Ever-smokers 26 (21.7%) 56 (21.5%) 4 (21.1%) 11 (39.3%) marginally increased in stage III: only one third of patients received Never-smokers 94 (78.3%) 205 (78.5%) 15 (78.9%) 17 (60.7%) chemoradiotherapy, mainly concurrently. Treatment variation seen Pathology between patient groups suggests tailored treatment decision, while Ad 103 (85.8%) 19 (100%) variation between hospitals and regions indicate differences in clinical SCC 14 (11.7%) 0 practice. SCLC 1 (0.8%) 0 Legal entity responsible for the study: The authors. Others 2 (1.7%) 0 Funding: This work was funded by the Dutch Association of Radiation TNM stage Oncology (NVRO) which had the opportunity, thanks to external funding, I 97 (80.8%) 17 (89.5%) to financially support this study. II 12 (10.0%) 0 III 6 (5.0%) 1 (5.3%) Disclosure: J. Evers: Research grant/Funding (institution: Dutch Association of Radiation Oncology (NVRO). L. Hendriks: Advisory/Consultancy, Research grant/ IV 1 (0.8%) 1 (5.3%) Funding (institution), Fees for institution - all not related to the work currently submitted: Boehringer Ingelheim; Advisory/Consultancy, Non-remunerated activity/ies, Fees for institution, non-remunerated support: local PI of pharma initiated research - all not related to the work currently submitted: BMS; Advisory/ Conclusions: The breath test with HPPI-TOFMS is feasible and highly Consultancy, Research grant/Funding (institution), Travel/Accommodation/ accurate for lung cancer detection and might have important implica- Expenses, Non-remunerated activity/ies, Fees for institution, travel support tions for future lung cancer screening. (self), non-remunerated support: local PI of pharma initiated research - all not

Journal of Thoracic Oncology Vol. 16 No. 4S: S711–S716 S712 Journal of Thoracic Oncology Vol. 16 No. 4S related to the work currently submitted: Roche Genentech; Research grant/ Funding (institution), Not related to the work currently submitted: AstraZeneca; Honoraria (self), Educational webinairs - not related to the work currently 32P submitted: Quadia; Advisory/Consultancy, Fees for institution - not related to the Patient experience and outcomes during lung cancer work currently submitted: Eli Lilly; Advisory/Consultancy, Fees for institution - treatment: A systematic review not related to the work currently submitted: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Non-remunerated activity/ies, Fees for S. Hussain Institute of Applied Health Research, The University of institution, non-remunerated support: local PI of pharma initiated research - all not related to the work currently submitted: MSD/Merck; Advisory/Consultancy, Birmingham - Medical School, Birmingham, UK Non-remunerated activity/ies, Fees for institution, non-remunerated support: local PI of pharma initiated research - all not related to the work currently Background: Lung cancer diagnosis can be challenging, resulting in submitted: Takeda; Non-remunerated activity/ies, Non-remunerated support: delays that may adversely affect survival, which could improve, if patients local PI of pharma initiated research - not related to the work currently submitted: follow a rapid diagnosis and treatment pathway (1). This review will Novartis; Non-remunerated activity/ies, Non-remunerated support: local PI of evaluate methods used to measure patient experience during lung cancer pharma initiated research - not related to the work currently submitted: GSK; Non- remunerated activity/ies, Non-remunerated support: local PI of pharma initiated treatment along with patient reported outcomes and assess outcomes research - not related to the work currently submitted: Blueprint Medicines; such as progression free survival by exploring the existing evidence, in Advisory/Consultancy, Fees for institution - not related to the work currently order to ensure that novel knowledge is contributed to the field. submitted: Amgen; Non-remunerated activity/ies, Non-remunerated support: Methods: This systematic review was registered on PROSPERO local PI of pharma initiated research - not related to the work currently submitted: Janssen Pharmaceuticals; Non-remunerated activity/ies, Non-remunerated (CRD42019126574), to study the effectiveness, safety and patient support: local PI of pharma initiated research - not related to the work currently reported outcomes/experiences among people undergoing investigation submitted: Mirati. M.J. Aarts: Research grant/Funding (institution) - not related to or treatment for lung cancer following different pathways. It further the work currently submitted: Amgen. All other authors have declared no conflicts investigated the nature of existing evidence to assess the patient of interest. reported outcomes and experience during SABR vs Surgery among patients with lung cancer. Standard systematic review methodology to eliminate sources of bias were employed, for example dual review at 31P abstract and full text stage. Lung cancer survival in Sri Lanka Results: The results of the review are in line with the findings of the lung cancer PROMS report published in 2010 stating that, “EORTC QLQ-LC13 L.R. Alagiyawanna1, S. Wijesekera1, V. Peiris1, D. Silva1, has a more robust body of evidence in the literature as compared to other T. Rupasinghe1, T. Skandarajah1, N. Jeyakumaran1, D. Gunasekera1, scales such as LCSS and FACT L” (2). The data based on the results of this N. Joseph2 1Oncology Department, National Cancer Institute of Sri Lanka, review suggests that the measure used most frequently is EORTC QLQ- Maharagama, Sri Lanka; 2Oncology Department, District General Hospital 30. A variation in the reporting as well as level of deterioration or Chilaw, Chilaw, Sri Lanka improvement in the QOL and PFS was observed across different modalities, which illustrates the impact of pathway being followed. Background: Lung cancer is the second commonest cancer among Conclusions: A variation in the reporting as well as level of deterioration males in Sri Lanka. Real world survival data is scarce, and we conducted or improvement in the QOL and PFS was observed across different a retrospective survival analysis among patients treated at the National modalities, which illustratesthe impact of pathway being followed. There is Cancer Institute of Sri Lanka, Maharagama. This is the first ever study on a need to collect PROM datafrom lung cancer patients and analyse NLCA as lung cancer survival in Sri Lanka. well as NCPES data to study patient experience, as it will help identify the Methods: All patients with primary lung cancer treated at three selected factors that influence patient experience and the type of information, units during 2015–2016 were included in the study. Data on decision aids and support patients require during lung cancer treatment. clinicopathological and treatment delivered were extracted from clinic Editorial acknowledgement: I am grateful to Prof Alice Turner and Dr records. Overall survival defined as time to death or loss to follow-up Ian Woolhouse for their comments and Eli Harris for developing the was considered the primary end-point. Univariate and Multivariate search strategy and running the searches at the Bodlean Librairies, analysis of survival was performed using the log-rank and Cox University of Oxford. I would also like to thank all the second reviewers proportional hazards model respectively. for their contribution. Results: The study population comprised 349 patients. Median age was Legal entity responsible for the study: Samia Hussain. 61 years and majority of patients (74%) were males. Adenocarcinoma Funding: Has not received any funding. (56%) was the commonest histological subtype followed by squamous Disclosure: The author has declared no conflicts of interest. cell carcinoma (26%), while 6% of patients had small cell lung cancer. 230/349 (63%) had systemic metastases and only 33/349 (9%) were treated with curative intent. Median overall survival was 12 months (95% CI 2–26) in patients treated with curative intent and there was no 33P significant difference between radical surgery and radiotherapy. Median Demographic differentials of lung cancer survival in overall survival was 3 months (95% CI 2–6 months) in those treated Bangladeshi patients palliatively. On multivariate analysis, female gender (p = 0.007, HR 0.67) and first line treatment with tyrosine kinase inhibitors (p < 0.001, HR M.R.R. Islam1, A.T.M.K. Hasan1, N. Khatun1, I. Ridi1, N. Ishrat1, 0.11) was associated with superior survival. S. Das1, F. Arjuman2, H.S. Ahmed3, F.A. Begum4, M.R. Islam1, Conclusions: More than 90% of Lung cancer patients in Sri Lanka are M. Rahman1, M.N. Karim5, A. Hossain1, M.N. Hossen1 1Medical treated with palliative intent. Further work is needed to identify patient Oncology Dept., NICRH - National Institute of Cancer Research & Hospital, and care pathway barriers to ensure diagnosis at an earlier stage. Dhaka, Bangladesh; 2Histopathology Dept., NICRH - National Institute of Legal entity responsible for the study: The authors. Cancer Research & Hospital, Dhaka, Bangladesh; 3Surgical Oncology, Funding: Has not received any funding. Bangabondhu Sheikh Mujib Medical University, Dhaka, Bangladesh; Disclosure: All authors have declared no conflicts of interest. 4Oncology, Bangladesh Specialized Hospitals Limited, Dhaka, Bangladesh; 5Public Health and Preventive Medicine, Monash University, Melbourne, Australia

Background: Lung cancer is the leading cause of cancer-related mortality and most common cancer in worldwide with more than a million deaths annually. Despite vigorous improvement in diagnostics April 2021 Abstracts S713 facilities and treatment modalities, the prognosis remains poor. The relatively frequent in men (24.7%) than in women (11.1%). There was evaluating demographic variables associated with survival in lung no significant difference in age of diagnosis, by histological type of lung cancer patients are useful as these generate data on prognostic variables, cancer. which could be used to develop models to disease prevention, predict Conclusions: Lung cancer is a serious and potentially deadly disease in treatment response and survival in newly detected lung cancer patients. Morocco. It is important to develop strategies that take into account the Methods: It is a retrospective cross-sectional study at national institute current trends in lung cancer and target particularly groups at risk. of cancer research & Hospital (NICRH), a tertiary care center at Dhaka, Legal entity responsible for the study: The authors. Bangladesh between 2018 and 2019. The Ethical Review Board of Funding: Has not received any funding. NICRH approved the study protocol. Survival estimate was generated Disclosure: All authors have declared no conflicts of interest. using Kaplan-Meier method and Univariate and multivariable cox proportional hazards regression was fit to assess the association of demographic factors. 35P Results: In the study 84.6% were males and 15.4% were females. About Lung cancer diagnosis and continuum of care: How did the 64% patients are between 50–69 years. 40% of the patients were COVID-19 outbreak impact? Data from an Italian multicenter underweight at time of diagnosis whereas 8.1% & 51.9% patient were overweight & normal weight respectively. Most of the patient had found study illiterate (66.2%). 55.4% patients found in low economic condition. L. Cantini1, G. Mentrasti1, N. La Verde2, M.S. Cona2, R. Chiari3, Around one third of the patient (29.5%) had comorbid condition. 4 5 3 6 6 Statistically significant difference in survival estimates is observed in 70 E. Martinelli , F. Morgillo , L. Nicolardi , A. Cortellini , V. Pensieri , V. Cognigni1, G. Pinterpe1, T. Galassi1, F. Pecci1, P. Mazzanti1, years and above age groups compare to less than 50 years age group (p < 1 1 1 1 0.001). Primary education completed group had better survival then the M. Di Pietro Paolo , R. Giampieri , R. Berardi AOU Ospedali Riuniti Ancona UniversitàPolitecnica delle Marche, Ancona, Italy; 2ASST illiterate group (P < 0.01), underweight patient group had worse 3 outcome compare to normal or over weight patient groups (P = 0.001). Fatebenefratelli Sacco, Milan, Italy; Oncologia Ospedali Riuniti Padova 4 ̀ No comorbidity group had better survival than comorbid group (p = Sud, Monselice, Italy; Department of Precision Medicine, Universita degli Studi della Campania Luigi Vanvitelli, Naples, Italy; 5Universitàdegli Studi 0.005). But the socioeconomical status (SES) and genderdid not showany 6 statistically significant result (p = 0.291 & p = 0.545 respectively. della Campania Luigi Vanvitelli, Naples, Italy; Medical Oncology Dept., ’ Conclusions: SES, education level, lack of resources and social stigma Ospedale Civile San Salvatore - ASL 1- Avezzano Sulmona L Aquila, ’ plays important role in survival outcome of lung cancer patients in L Aquila, Italy Bangladesh. The demographic variables related survival in lung cancer Background: The coronavirus disease 2019 (COVID-19) pandemic has needs to be fully elucidated because of its importance in the design of become a huge health emergency, with Italy being one of the most experimental protocols for targeted chemoprevention, early screening, heavily affected countries. Cancer patients (pts), especially those with and individualized treatment. lung cancer (LC), represent a very frail population, and multiple efforts Legal entity responsible for the study: The authors. need to be taken by Oncology Departments to guarantee diagnostic- Funding: Has not received any funding. therapeutic pathways (DTP). Aim of this multicenter Italian study is to Disclosure: All authors have declared no conflicts of interest. assess whether the COVID-19 outbreak impacted the LC pts’ likelihood of receiving timely diagnosis and access to treatment. Methods: Medical records of all consecutive newly diagnosed LC pts 34P referred to five Italian Oncology Departments between March and Sex and age differences in primary lung cancer in Morocco: An August 2020 were reviewed. Access rate (number of pts/days) and epidemiologic study temporal intervals between date of symptoms onset, radiological diagnosis, cytohistological diagnosis, and treatment start were com- O. Erefai, A. Soulaymani, A. Mokhtari, H. Hami Faculty of Science, Ibn puted and compared with those of the same period in 2019. Differences ’ Tofail University, Kenitra, Morocco between the two years were analyzed using Fisher s exact test or chi- square test for categorical variables and unpaired Student t test, or the Background: Lung cancer is a leading cause of death worldwide. In Mann-Whitney U test for continuous variables. Morocco, it is the most commonly occurring cancer in men. The aim of Results: Although a slight reduction in newly diagnosed LC cases was this study is to determine the epidemiological and histological profile of seen when compared with 2019 (89 vs 100, access rate ratio = 0.88, p = primary lung cancer in Rabat (capital of Morocco) over a 4-year period, 0.25), that was not significant. Newly diagnosed LC patients in 2020 from 2014 to 2017, by sex and age. were more likely to be current smokers (45% vs 29%, p = 0.04). Other Methods: This is a descriptive retrospective study of all patients with clinical and tumor characteristics were similar regardless of the year. primary lung cancer diagnosed and treated at Ibn Sina University Looking at pts management, no differences emerged in terms of interval Hospital Center in Rabat during the period from January 2014 to between symptoms onset and radiological diagnosis (median 30.5 vs 25 December 2017. The data were collected from medical records for each days, p = 0.96), symptoms onset and cytohistological diagnosis (46 vs 49 patient. Statistical analysis was performed using Epi InfoTM7. days, p = 0.56), symptoms onset and treatment start (median 70.5 vs 81 Results: During the period of study, 574 new cases of primary lung days, p = 0.42), cytohistological diagnosis and treatment start (29 vs 29 cancer were diagnosed. Of these, 87.5% were men and 12.5% were days, p = 0.91). women, giving a male-female ratio of 7. The average age of patients at Conclusions: Despite the unprecedented times, our data provide a diagnosis was 58.4 years (range 21–85 years). There was no significant valuable insight on how the Italian Health Care System first response to gender difference in average age. The age distribution show that 19.9% COVID-19 emergency was able to ensure the DTP standards of LC pts. of patients were aged less than 50 years, 29.7% were in the 50–59-year Considering the clinical spectrum of LC onset and potential overlap with age group, 33.8% were aged between 60 and 69 years and 16.5% were COVID-19 disease, further investigations are warranted to provide an aged 70 years and older. According to the results, 7.3% of lung cancers exhaustive picture to optimally address quality of care issues in the were small cell lung cancer (SCLC) and 90.9% were non-small cell lung ongoing pandemic. cancer (NSCLC). Adenocarcinoma was the most frequent cell type of lung Legal entity responsible for the study: The authors. cancer, with 60.45%, followed by squamous cell carcinoma, with 23%. Funding: Has not received any funding. According to gender, adenocarcinoma was more common in women Disclosure: All authors have declared no conflicts of interest. (70.8%) than in men (58.4%), while squamous cell carcinoma was S714 Journal of Thoracic Oncology Vol. 16 No. 4S

Early detection still plays a key role in providing a chance of curable 36P treatment for patients. In Vietnam, to date, there is no official clinical Cost-effectiveness of lung cancer screening with low-dose guideline for lung cancer (LC) screening using low-dose computed computed tomography in China: A modeling study tomography (LDCT). Methods: Two thousand eight hundred and five patients were screened – Y. Du1,Y.Li2, G. Sidorenkov1,Z.Ye2, R. Vliegenthart3, with LDCT over 4 years (1/2017 10/2020), all detected nodules were M.A. Heuvelmans1, M. Dorrius3, H.J.M. Groen4, S. Liu5,L.Fan5, classified according to Lung-RADs from the American College of M.J.W. Greuter3, G.H. de Bock1 1Epidemiology, UMCG - University Radiology (ACR). Biopsies were done for nodules greater than 1 cm Medical Center Groningen, Groningen, Netherlands; 2Tianjin Medical and approachable, otherwise video-assisted thoracoscopy was indicated University Cancer Institute and Hospital, Tianjin, China; 3Radiology, for non-approachable nodules with highly suspicious cancerous nodules UMCG - University Medical Center Groningen, Groningen, Netherlands; (Lung-RADS 4A and greater). – 4Pulmonary Diseases, UMCG - University Medical Center Groningen, Results: 2805 patients were aged 20 92 years old (49.7 ± 12.6); 1508 Groningen, Netherlands; 5Radiology, Shanghai Changzheng Hospital, patients (53.8%) were less than 50 years-old, only 114 patients (4%) Shanghai, China were reported as smokers, 2508 new patients and 297 (10.6%) repeated scanned patients, 183 patients (6.5%) were detected a non-calcified Background: Smoking is considered not the only major risk factor that nodules, 13 out of 183 (7.1%) nodules were graded Lung-RADS 4A and contributing to the lung cancer incidence in China, due to the fact that 4B, and then four lung cancers were diagnosed with stage 1 (3/2805 about half of patients with lung cancers are never-smokers. Considering scanned patients; 0.1%). the potential of the implementation of lung cancer screening in the Conclusions: LDCT was overused in clinical practice for lung cancer general Chinese population, this study aimed to assess the potential cost- screening and the cancer detection rate among scanned patients was effectiveness of lung cancer screening with low-dose CT in a general very low. A recommendation for standardized lung cancer screening population in China. guidelinse in Vietnam is a crucial and essential for appropriately Methods: We applied a micro-simulation model on lung cancer screen- indicating LDCT that will maximize its advantages and restrict ing, which has been previously validated. The model simulated acohort of overusage. general population on a lifetime horizon. The data for modeling included Legal entity responsible for the study: Vinmec Times City life expectancy, natural history of lung cancer, screening sensitivity and International Hospital, Hanoi, Vietnam. specificity, and costs. These input data were collected from national and Funding: Has not received any funding. international sources. A healthcare system perspective was adopted to Disclosure: All authors have declared no conflicts of interest. assess the costs included in the model. The evaluated screening scenarios were the different combinations of screening interval, and start and stop age of screening. The outputs of the model included costs (valued in 38P Chinese Yuan, CNY) and life-years in the presence and absence of Brain metastases in non-small cell lung cancer in era of screening. The costs and life years were discounted by 3%. Additional molecularly driven therapy costs and life years gained relative to no screening were calculated. All results were scaled to 1000 individuals. The average cost-effectiveness S. Rakshit1, R. Bansal2, A. Desai1, K. Leventakos3 1Hematology- ratio (ACER) was calculated by dividing the additional costs by the life Oncology, Mayo Clinic, Rochester, MN, USA; 2Hematology, Mayo Clinic, years gained relative to no screening. The willingness-to-pay threshold of Rochester, MN, USA; 3Oncology Department, Mayo Clinic, Rochester, MN, CNY 213k per life years gained was applied. USA Results: The evaluated screening scenarios yielded 21–33 life years gained in men and 10–14 life years gained in women relative to no Background: Patients with non-small cell lung cancer (NSCLC) who screening. For men, biennial screening yielded an ACER of CNY 184 k– develop brain metastases (BM) historically have worse outcomes. In the 216 k per life years gained. Biennial screening from age 55 to 75 years was era of targeted therapy, drugs with CNS activity may have improved cost-effective and optimal with the defined threshold and resulted in an outcomes. We aim to evaluate incidence of brain metastases in patients ACERof CNY 188 k per lifeyears gained.For women, the ACER ranged from with driver mutations and evaluate survival outcomes. CNY 398 k to 808 k per life years gained across the evaluated scenarios. Methods: We collected lung gene panel data at Mayo Clinic between Conclusions: Lung cancer screening with low dose CT in the general August 2015 and June 2020. We then identified patients with different population can be cost-effective for men, but not for women in China. driver mutations. Clinical data was collected by retrospective review of Biennial screening between age 55 and 75 years would be the optimal electronic medical records. Patients with recurrent NSCLC or metastatic strategy for men. disease were included for analysis. Survival analysis was done using Legal entity responsible for the study: The authors. Kaplan-Meier and difference was assessed using log-rank test. Funding: Has not received any funding. Results: We identified a cohort of 98 patients with targetable molecular Disclosure: All authors have declared no conflicts of interest. alterations (excluding KRAS). Most common alterations were EGFR (52%), MET (13.7%), ALK (11.7%). Overall 31% of patients were noted to have BM at diagnosis while 7% additional patients developed BM 37P during their disease course. RET and BRAF mutated patients had the Emerging usage of low-dose computed tomography scanning highest incidence of BM at diagnosis (100% and 43% respectively) in lung cancer screening: A single Vietnamese institutional while overall RET and EGFR mutated patients had highest prevalance of assessment BM (100% and 45% respectively). Local treatment of BM included radiation alone in 63%, surgery plus radiation in 23% and no local treatment in 14%. Targeted treatment was given in 69% of patients. The D.T. Hiep1, H.M. Nguyen2, H. Nguyen2 1Vinmec Times City International median survival was 32 months irrespective of presence or absence of Hospital, Hanoi, Vietnam; 2Oncology Center, Vinmec Times City BM. No statistically significant difference in survival outcomes was International Hospital, Hanoi, Viet Nam observed between patients with BM at diagnosis/ disease course versus Background: Globocan 2018 showed that Vietnam had more than no BM. 26,000 new lung cancer cases in both sexes, the second most common cancer incidence constituting 14.5% of all new cancer cases nationwide. April 2021 Abstracts S715

0.754. All the p values were <0.001. Two cases were negative by all three Table 38P: Incidence of BM at diagnosis in different mutations assays and were positive on NGS as these were non-canonical and non- BM at hotspot mutations not incorporated in the primer sets of any of the Gene diagnosis assays in question. The Z statistics score was 25.4 and Cronbachs alpha EGFR (n = 53) 19 (36%) was 0.973 for cobas compared to tissue, and they were 6.91 and 0.8008 MET (n = 14) 3 (21%) for ddPCR respectively. ALK (n = 12) 4 (33%) Conclusions: From this first experience from India, the advantages of ERBB2 (n = 8) 1 (13%) upfront liquid biopsy are evident, and adopting the same, may prove BRAF (n = 7) 3 (43%) promising in a clinician’s armamentarium. Cobas has advantages of ROS (n = 2) 0 (0%) broader mutation spectrum compared to ddPCR, however is limited by RET (n = 2) 2 (100%) sensitivity, whereas ddPCR is limited by specificity although can provide absolute quantification. Legal entity responsible for the study: Ullas Batra. Conclusions: In the analyzed cohort of patients, we note that patients Funding: Has not received any funding. with NSCLC with driver mutations have a high incidence of BM at Disclosure: All authors have declared no conflicts of interest. diagnosis. Contrary to historical controls, these patients with molecular alterations have favorable outcomes despite development of BM. This could be due to the availability of potent active targeted drugs with good CNS penetration. 40P Legal entity responsible for the study: Sagar Rakshit. Revealing the association between lung cancer and allergic Funding: Has not received any funding. respiratory diseases: Meta-analysis of cohort studies Disclosure: K. Leventakos: Honoraria (institution): Takeda; Honoraria (institution): OncLive; Honoraria (institution): AstraZeneca. All other authors have B.P. Putra1, F.N. Putra2 1Dr. Soetomo Hospital-Airlangga University declared no conflicts of interest. Medical School, Surabaya, Indonesia; 2Faculty of Medicine Universitas Airlangga, Surabaya, Indonesia

39P Background: The nonclassical Th2-shifted inflammation and regulatory Tissue vs. cobas vs. DDPCR for EGFR in NSCLC: Real-world immune subsets in allergy patients can lead to immune suppression that evidence from India may cause tumours to escape from immune elimination. Previous studies suggest any associations between allergic respiratory diseases and lung cancer development although the results were still inconclu- U. Batra1, M. Sharma1, S. Nathany2, H. Singh1, P. Jain1, A. Mehta3 1 sive. This study aims to measure the association between lung cancer Medical Oncology, Rajiv Gandhi Cancer Institute & Research Center, New and allergic respiratory diseases. Delhi, India; 2Molecular Diagnostics, Rajiv Gandhi Cancer Institute & 3 Methods: We did both hand-searching and comprehensive searching in Research Center, New Delhi, India; Pathology, Rajiv Gandhi Cancer online databases of Pubmed, EMBASE, ScienceDirect, and The Cochrane Institute and Research Centre, New Delhi, India Library, to include all relevant studies from January 2000 until January Background: EGFR mutant adenocarcinoma accounts for almost 33% 2021. We included all cohort studies that access the lung cancer risk in cases of NSCLC in the Asian population. Single gene testing on tissue allergic respiratory diseases patients of asthma, allergic rhinitis (AR), blocks has been the gold standard since its discovery, however owing to and chronic rhinosinusitis (CRS) due to AR, then excluded studies with the inherent technical difficulties, invasive nature, difficult accessibility smokers, chronic bronchitis, chronic obstructive pulmonary disease to the lung may limit its use in many patients. Liquid biopsy has evolved (COPD), and previous cancer history patients. Bias risk was accessed as a value added tool for early diagnosis of biomarkers in lung cancer. with The Newcastle-Ottawa Scale for cohort studies. We performed Various detection methods have been employed for the detection of analysis to provide pooled risk ratios (RR) with 95% confidence interval EGFR mutation like Cobas V2 and ddPCR. This study was done to (CI) using random-effect heterogeneity test. evaluate the concordance of these techniques against the tissue biopsy Results: We included 18 cohort studies met our inclusion criteria. for primary EGFR mutation detection. Asthma patients have significant incremental of lung cancer risk (pooled Methods: 117 patients of NSCLC between April 2020-September 2020 RR = 1.43, 95% CI 1.22–1.67, p < 0.00001, I2 = 96%), but allergic were evaluated for primary EGFR mutations by therascreen, DDPCR and rhinitis patients are significantly protected against lung cancer risk Cobas V2. Statistical analysis was done using SPSS version 23, using (pooled RR = 0.81, 95% CI 0.70–0.95, p = 0.009, I2 = 52%). The overall descriptive statistics and kappa agreement. analysis suggests that allergic respiratory diseases patients have Results: Primary EGFR testing was done in 117 samples. The positivity significantly increased lung cancer risk (pooled RR = 1.26, 95% CI rate for cobas was 45.6% and that for ddpCR was 28.6%. The 1.08–1.46, p = 0.002, I2 = 98%). Surprisingly, allergic rhinitis patients concordance between tissue and cobas EGFR mutation was 96.33%. who have developed CRS are significantly vulnerable against lung cancer Considering tissue as gold standard, the ROC analysis depicted an AUC of (pooled RR = 2.18, 95% CI 1.13–4.22, p = 0.02, I2 = 78%). 0.923 for cobas and 0.800 for DDPCR, implying a sensitivity of ∼92% for Conclusions: Asthma and chronic rhinosinusitis increase lung cancer cobas and 80% for DDPCR. Mutation specific sensitivities also showed risk, while allergic rhinitis might be protective against lung cancer risk. similar trends, except for T790M for which sensitivity of ddPCR was Nevertheless, further studies are needed to establish the association. 50% with a specificity of 100% compared to 50% and 80% with cobas. Legal entity responsible for the study: The authors. Uncommon mutations had 0% sensitivity and specificity for ddPCR, as Funding: Has not received any funding. these cannot be detected by this assay. The AUC for ddpcr vs cobas was Disclosure: All authors have declared no conflicts of interest. S716 Journal of Thoracic Oncology Vol. 16 No. 4S

cancer risk in GERD and H. pylori infection patients. Bias risk was 41P accessed with The Newcastle-Ottawa Scale for observational studies. Increased lung cancer risk in gastroesophageal reflux disease Analysis was performed to provide pooled risk ratios (RR) with 95% and Helicobacter pylori infection patients: Systematic review confidence interval (CI) using random-effect heterogeneity test. and meta-analysis Results: We included 5 cohort and 4 cross-sectional studies met our inclusion criteria. Analysis of 3 GERD cohort studies suggests that GERD increase lung cancer risk significantly (pooled RR = 1.47, 95% CI 1.13– B.P. Putra1, F.N. Putra2 1Dr. Soetomo Hospital-Airlangga University 1.91, p = 0.004, I2 = 70%). Significant incremental lung cancer risk in Medical School, Surabaya, Indonesia; 2Faculty of Medicine Universitas H. pylori infection was shown in both cohort (pooled RR = 1.55, 95% CI Airlangga, Surabaya, Indonesia 1.10–2.18, p = 0.01, I2 = 39%) and non-cohort (pooled RR = 2.06, 95% Background: Gastroesophageal reflux disease (GERD) and Helicobacter CI 1.22–3.46, p = 0.006, I2 = 62%) studies analysis, thus the overall pylori infection are globally prevalent diseases. Recent studies suggested analysis also suggests significantly increased lung cancer risk in H. pylori that GERD is associated with increased lung cancer risk although the infection patients (pooled RR = 1.74, 95% CI 1.30–2.33, p = 0.0002, I2 = results were still inconclusive. Previous studies also suggested that lung 50%). cancer is an extra-gastric manifestation of H. pylori infection although Conclusions: Gastroesophageal reflux disease and Helicobacter pylori the results were inconsistent. This study aims to measure the lung cancer infection increase lung cancer risks. However, further studies are needed risk in the GERD and H. pylori infection patients. to establish the causalities. Methods: We did comprehensive searching in online databases of Legal entity responsible for the study: The authors. Pubmed, EMBASE, ScienceDirect, and The Cochrane Library, to include Funding: Has not received any funding. all relevant studies from January 2000 until January 2021. We included Disclosure: All authors have declared no conflicts of interest. all observational studies particularly cohort studies, that access the lung ABSTRACTS

incidental findings, but the information about the rate of their incidental IMAGING AND STAGING detection in our country is lacking. The purpose of this study was to examine recent trends in incidental pulmonary lesion identification in 42P hospitalized patients in Georgia and to find out if the percentage of Radiation induced pneumonitis in the era of the COVID-19 accidentally discovered pulmonary lesions on CT scans would be different in patients with confirmed COVID-19 disease versus in patients pandemic: Artificial intelligence for differential diagnosis who were COVID-19 free. Methods: We retrieved the electronic records of performed CT scans of S. Ramella1, C.C. Quattrocchi2, E. Ippolito1, F.M. Giordano2, hospitalized patients and calculated the number of accidentally C. Greco1, C.A. Mallio2, B. Santo1,P.D’Alessio2, M. Fiore1, discovered lung lesions throughout 3 consecutive months and analyzed R.M. D’Angelillo3, B. Beomonte Zobel2 1Radiation Oncology, Campus the data. We divided the data into two categories: results from confirmed Bio-Medico University, Rome, Italy; 2Diagnostic Imaging and COVID-19 cases and results from Covid-free patients. Interventional Radiology, Campus Bio-Medico University, Rome, Italy; Results: From the retrieved total of 2498 performed CT records, 2384 3Radiation Oncology, Tor Vergata University, Rome, Italy matched the inclusion criteria (with an inclusion rate of 95%). Background: In 2019, the Severe Acute Respiratory Syndrome Suspicious lung lesions were detected in a total of 181 patients Coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China. The most (4.3%); Out of which: 32% – single pulmonary nodules; 15.5% – a lung serious clinical entity associated with SARS-CoV-2 is a severe interstitial mass; 13% – multiple pulmonary nodules; 41.9% – Otherwise pneumonia that can lead to acute respiratory distress. Radiation undefined, suspicious pulmonary lesion. From the total of 2384 cases, pneumonitis (RP) is lung radiation toxicity. RP and SARS-CoV-2 COVID-19 was confirmed in 1316 patients (55%). Suspicious lung interstitial pneumonia show overlapping clinical features. The aim of lesions were detected in 86 (6.5%) of patients. Out of which: 26.7% – this study is to test the performance of a deep learning algorithm in single pulmonary nodules; 16% – a lung mass; 14% – multiple discriminating RP from COVID-19 pneumonia. pulmonary nodules; 43% – Otherwise undefined, suspicious pulmonary Methods: Seventy patients were analysed, 34 affected by COVID-19 lesion. From the total of 2384 cases, 1140 were COVID-free (47.8%). pneumonia and 36 by RP. The CT images were analyzed by InferReadTM Suspicious lung lesions were detected in 95 (8.9%) of patients. Out of CT Lung (COVID-19) ®, an Artificial Intelligence algorithm based on a which: 37% – single pulmonary nodules; 15% – a lung mass; 13% – novel deep convolutional neural network structure. In a previous multiple pulmonary nodules; 41% – Otherwise undefined, suspicious publication the cut-off value of the estimated risk probability of COVID- pulmonary lesion. 19 was set at levels higher than 30% (“COVID19 High Risk”), as the Conclusions: We conclude that the percentage of incidentally dis- percentage of COVID-19 confirmed patients above this cut-off value was covered pulmonary lesions in hospitalized patients in the given period is higher than 95%. Values of estimated risk probability below 30% were 4.3% in Georgia and this number is not significantly different in patients classified as “COVID19 Low Risk”. Statistical analysis included Mann with or without confirmed COVID-19 disease. Additional research is Whitney U test (significance threshold at p < 0.05) and ROC curve with required for a better understanding of the results. fitting performed by using the maximum likelihood fit of a binormal Legal entity responsible for the study: The authors. model. Funding: Has not received any funding. Results: The algorithm classified as “COVID19 Low Risk” 66.7% of Disclosure: All authors have declared no conflicts of interest. patients presenting RP. All RP classified as “COVID19 High Risk” were ≥G3. The algorithm showed good accuracy in the detection of RP against COVID-19 pneumonia (sensitivity = 97.0%, specificity = 2%, AUC = 44P 0.72). This accuracy increased when cut-off of 30% was Inter-reader variability of lung parenchymal observations on applied (sensitivity 76%, specificity 63%, AUC = 0.84. The total lung chest CT among COVID-19 RT-PCR negative lung cancer volume (p = 0.001), the left lower lobe (p < 0.001) and the right lower patients treated with chemo-radiation: Potential pitfalls of lobe (p < 0.001) involvement resulted increased in COVID-19 group compared to RP. In patients pretreated with radiotherapy and presenting pulmonary findings in different readers with various diffuse pneumonitis classified by AI as COVID19 High Risk a combination experience levels of dosimetric factors may help to identify RP (PPV increased from 60% 1 2 3 3 1 4 to 99.8%). A. Jajodia , H. Prosch ,U.Batra , B. Amrith , J. Goyal , S. Pasricha , 4 3 1 1 1 Conclusions: Deep-learning algorithm can help to discriminate RP from A. Mehta , D.C. Doval , S. Puri , A. Chaturvedi Radiology COVID-19 pneumonia, classifying most RP as Low-risk COVID19. In Department, Rajiv Gandhi Cancer Institute and Research Centre, New 2 patients classified as high risk, treated with radiation therapy also Delhi, India; Radiology Department, Medical University of Vienna, 3 dosimetric factors should be taken into account. Vienna, Austria; Medical Oncology Department, Rajiv Gandhi Cancer 4 Legal entity responsible for the study: The authors. Institute and Research Centre, New Delhi, India; Pathology, Rajiv Gandhi Funding: Has not received any funding. Cancer Institute and Research Centre, New Delhi, India Disclosure: All authors have declared no conflicts of interest. Background: To assess inter reader variability of lung parenchymal observations in treated lung cancer patients with initially negative RT- PCR result for COVID 19, among radiologists with various experience 43P levels. Incidentally discovered suspicious lung lesions in hospitalized Methods: Three radiologists with different levels of clinical experience patients during the COVID-19 pandemic in Georgia in interpretation of chest CT study (range, 4–25 years), rated studies as treatment related pneumonitis (either drug or radiation related), post M. Abuladze1, K. Saganelidze1, D. Barabadze1, M. Kavtaria1 1New COVID related changes or infective etiological process [other than – Vision University, Tbilisi, Georgia COVID], from a scale of 1 3 (1: negative, 2: indeterminate, 3: positive finding), in a cohort of 47 patients. Each radiologist was blinded to Background: Since the start of the COVID-19 pandemic, chest CT has clinical history and interpreted annotated scans while recording been broadly used for diagnosing and monitoring Covid-19 pneumonia observations on an excel sheet. Interobserver agreement was assessed in hospitalized patients in Georgia. Pulmonary lesions are common with kappa statistic. Final confirmation was based on bronchoalveolar

Journal of Thoracic Oncology Vol. 16 No. 4S: S717–S719 S718 Journal of Thoracic Oncology Vol. 16 No. 4S lavage and lab parameters including repeat RT-PCR. Reasons for patient pathway was comparable to reports from other countries and differences were analysed on a case-by-case basis. showed a 4-day increase during the study period, mainly due to longer Results: The overall interobserver agreement between all readers was treatment intervals with more specific examinations. The detailed substantial (k = 0.624; 95% CI, 0.56–0.69; p < 0.001). The 3 point analysis of the patient pathway allowed for the detection of temporal scoring system was dichotomized as positive for confirmed pathology trends as well as disparities among patient subgroups, highlighting that and negative/indeterminate grouped under one. The inter-observer there is still room for improvement to optimize the timeliness of lung agreement for the dichotomized scaling between all readers was almost cancer care. perfect (k = 0.834; 95% CI, 0.76–0.89; p < 0.001). In 32 patients, all Clinical trial identification: 10338-5/2019/EKU. radiologists agreed on the differentiation of negative and indeterminate/ Legal entity responsible for the study: MSD Pharma Hungary Ltd. positive finding, while in 15 cases disagreement between readers led to Funding: MSD Pharma Hungary Ltd. different scoring assignment. While the gold standard for COVID19 was Disclosure: Z. Kiss: Full/Part-time employment: MSD Pharma Hungary Ltd. RT-PCR test, but decreased sensitivity of the same led to erroneous A. Vastag: Full/Part-time employment: MSD Pharma Hungary Ltd.; Z. Polanyi:́ Full/ scoring on CT chest, which has higher sensitivity. Part-time employment: MSD Pharma Hungary Ltd. A. Daniel: Full/Part-time employment: MSD Pharma Hungary Ltd. B. Nagy: Research grant/Funding Conclusions: Our study showed substantial interobserver variability for (institution): MSD Pharma Hungary Ltd. G. Rokszin: Honoraria (self): MSD the classification of lung parenchymal observations during ongoing Pharma Hungary Ltd. Z. Abonyi-Toth:́ Honoraria (self): MSD Pharma Hungary Ltd. pandemic of COVID 19. Z. Barcza: Honoraria (self): MSD Pharma Hungary Ltd. Z. Voko:́ Research grant/ Legal entity responsible for the study: The authors. Funding (institution): MSD Pharma Hungary Ltd. All other authors have declared no conflicts of interest. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest. 46P Comparision of 7th and 8th editions AJCC/UICC TNM staging in 45P correlation with survival and treatment guidelines for non- Analysis of lung cancer patient pathway: A 6-year nationwide small cell lung cancer analysis from Hungary T.W. Irura1, A. Ashour1, O.S. Zahra1 1Clinical Oncology, Alexandria K. Bogos1, G. Gaffly2, Z. Kiss3, L. Tamási4, G. Ostoros1,V.Müller4, Clinical Oncology Department, Alexandria, Egypt L. Urbán5, N. Bittner6,V.Sárosi7, A. Vastag3, Z. Polányi3, A. Daniel3, B. Nagy8, G. Rokszin9, Z. Abonyi-Tóth9, Z. Barcza10, J. Moldvay2, Background: In Egypt, lung cancer is the most lethal malignancy. Most Z. Vokó11 1National Koranyí Institute of Pulmonology, Budapest, patients present with locally advanced or metastatic disease. The aim of Hungary; 2Pulmonology Hospital Törökbalint,́ Törökbalint,́ Hungary; the study is to review all demographic and clinic-pathological features of 3MSD Pharma Hungary Kft., Budapest, Hungary; 4Department of Non- Small Cell Lung Cancer (NSCLC) patients, treatment lines received Pulmonology, Faculty of Medicine, Semmelweis University, Budapest, and then evaluate the discriminatory ability of the new 8th American Hungary; 5Matrahaza Healthcare Center and University Teaching Joint Committee on Cancer (AJCC)/International Union for Cancer Hospital, Matrahá za,́ Hungary; 6Pulmonology Clinic University of Control (UICC) staging system edition T category, M category and Debrecen, Debrecen, Hungary; 7Faculty of Medicine, University of Pecs,́ compare it with the 7th edition. Pecs,́ Hungary; 8Eötvös Lorand́ University, Budapest, Hungary; 9RxTarget Methods: In this retrospective population-based cohort, data on patient Ltd., Szolnok, Hungary; 10Syntesia Ltd., Budapest, Hungary; 11Semmelweis characteristics, tumor characteristics, diagnostic tools used to reach a University, Budapest, Hungary diagnosis and treatment modalities administered has been collected from the archive of Alexandria Clinical Oncology Department. The study Background: This study aimed to examine the characteristics of the lung participants included all NSCLC patients who fulfilled the inclusion cancer (LC) patient pathway in Hungary during a 6-year period. criteria. Methods: Methods This nationwide, retrospective study included Results: 222 patients fulfilled the criteria to be included in the study.192 patients newly diagnosed with LC (ICD-10 C34) between January 1, patients in the 7th edition and 30 in the 8th edition. Male predominance 2011 and December 31, 2016 using data from the National Health (82.8%) in 7th edition and (80%) in 8th edition. The mean age of Insurance Fund (NHIF) of Hungary. Following patient pathway intervals diagnosis is 58.8years (ranging from 23 to 84) in the 7th edition and were examined: system-, diagnostic- and treatment interval by age, 65.0years (ranging from 40 to 82) in the 8th edition. Surgery was done gender, tumor type, study year and first-line LC therapy. on 8.1%, concomittant chemo-radiotherapy on 9.9% cases overall. The Results: Results During the 6-year study period, 17,386 patients had at 7th edition 87.5% and 76.7% of patients received chemotherapy. When least one type of imaging (X-ray or CT/MRI) prior to diagnosis. The we used tumor size to categorize the patients, according to the 7th median system interval was 64.5 days, and it was 5 days longer among edition AJCC TNM stage, T1a and T1b 0 patients, T2a 15 (7.8%) patients, women than in men (68.0 vs. 63.0 days). The median system interval T2b 18(9.4%) patients, T3 23(12%) patients, T4 136(70.8%) patients. difference in patients with adenocarcinoma (n = 7,474) compared to According to the 8th edition of AJCC TNM stage, T1a,T1b, T1c, T2a 0 those with squamous cell carcinoma (n = 4,674): 70.4 days (IQR: 47–99) patients, T2b 5 patients (16.7%) T3 7 patients (23.3%) T4 18 patients vs. 64.0 days (IQR: 42.5–94) was significantly longer by 6.4 days (p < (60%). We were able to draw that survival time decreases as the 0.001), the shortest median system interval was recorded among pathological stage progresses. The 8th edition was shown to be more patients diagnosed with small cell lung cancer (n = 2,353; median: 48.0 discriminatory in showing this. The median PFS was 6months between days IQR: 30–74). Patients who received surgery as first-line treatment the first line(cisplatin based) P value 0.114 and second line of had significantly longer median system intervals compared to those chemotherapy. Factors such as N stage (P < 0.001), pleural invasion receiving chemotherapy (81.4 days vs. 62.0 days). The mean diagnostic and vessel invasion were associated significantly with DFS. imaging interval decreased by 3.43 days from 24.33 to 20.90 days (p < Conclusions: The 8th edition of AJCC/TNM staging seems to be more 0.001), on the other hand, the mean diagnostic biopsy interval increased superior than the 7th edition in both treatment guidelines and by 3.31 days (p < 0.001), and the mean treatment interval also increased predicting survival. by 4.09 days (p < 0.001) during the 6-year study period. Legal entity responsible for the study: University of Alexandria. Conclusions: This nationwide retrospective study provides valuable Funding: Has not received any funding. insights into the characteristics of the lung cancer patient pathway in Disclosure: All authors have declared no conflicts of interest. Hungary and its changes over a 6-year period. The length of the whole April 2021 Abstracts S719

Methods: RYTHMIC (Reseaú tumeurs THYMiques et Cancer) is a French 47P nationwide network mandated to systematically discuss every case of Central nervous-system (CNS) metastases in thymic epithelial TET. The database, hosted by IFCT (Intergroupe Francophone de ́ tumours (TET): Real-world insight from RYTHMIC Cancerologie Thoracique), prospectively includes all consecutive pts with a diagnosis of TET discussed in RYTHMIC national or regional J.C. Benitez1, M-E. Boucher2, E. Dansin3, M. Kerjouan4, tumor boards. We analysed epidemiologic, clinical and pathological L. Bigay-Game5, E. Pichon6, F. Thillays7, P. Falcoz8, S. Lyubimova9, characteristics of pts with TET and CNS metastasis during cancer history. Y. Oulkhouir10, F. Calcagno11, L. Thiberville12, Results: From January 2012 to December 2019, 2909 pts were included C. Clément-Duchêne13, V. Westeel14, P. Missy15, P.A. Thomas16, in the database, including 248 TC (8.5%). The median age at diagnosis T. Molina17, N. Girard18, B. Besse19 1Dept. Medical Oncology, Gustave was 63.5 (range 9 to 91). There were 14 pts with CNS metastases during 2 cancer history; 5 (35.7%) at diagnosis, of them 3 with isolated CNS Roussy - Cancer Campus, Villejuif, France; Gustave Roussy - Cancer st nd 3 4 lesions (retro-orbital lesion for the 1 , a cerebellum nodule for the 2 Campus, Villejuif, France; Centre Oscar Lambret, Lille, France; Centre rd Hospitalier Universitaire de Rennes, Rennes, France; 5Centre Hospitalier and multiple lesions for the 3 ) and 2 with extracerebral lesions. Among Universitaire de Toulouse, Toulouse, France; 6Services de Pneumologie, the 14 pts, half were men. None of the pts reported any AID. 12/14 CHRU de Tours, Hôpital Bretonneau, Tours, France; 7Institut de (85.8%) pts were diagnosed of TC and 2 (14.2%) of a thymoma A and B3. Cancerologié de l’Ouest, Rouen, France; 8Centre Hospitalier Universitaire A surgical biopsy was performed and the histological subtype for non-TC de Strasbourg, Strasbourg, France; 9Centre Hospitalier Universitaire de tumours was centrally confirmed. In 9 (64.3%) pts, CNS was a – Montpellier, Montpellier, France; 10Centre Hospitalier Universitaire de recurrence event with a median of 9 months (95%CI 5.5 12.55) after Caen, Caen, France; 11Centre Hospitalier Universitaire de Besançon, diagnosis. Median follow-up was 28 months. Median overall survival – Besançon, France; 12Hop. Charles Nicolle, Rouen, France; 13Institut de (OS) was 22 months (95%CI 9.8 34.2). OS tend to be better when CNS Cancerologié de Lorraine, Nancy, France; 14CHRU Besançon - Hopital Jean were found at diagnosis vs. relapse (not reached vs. 17 moths) Minjoz, Besançon, France; 15French Cooperative Thoracic Intergroup, and, median progression free survival (PFS) was 13 vs. 8 months Paris, France; 16Thoracic Surgery Department, Aix-Marseille University - respectively. No differences between histological subtypes (9 vs. 8 Facultéde Medeciné Nord, Marseille, France; 17Hôpital Universitaire months for no TC vs. TC respectively). No greater risk of recurrence was – Necker Enfants Malades, Paris, France; 18Thorax Institute, Institut Curie, seen for CNS metastases found at diagnosis (OR = 0.6, 95%CI. 0.29 1.22; Paris, France; 19Cancer Medicine Department, Institut Gustave Roussy, p = 0.04). Villejuif, France Conclusions: The prevalence of CNS disease was extremely rare in our cohort (0.48%). CNS metastases have been reported at diagnosis and Background: TET are rare malignancies that range from indolent at progression mainly for thymic carcinoma in which the incidence was thymoma A to aggressive thymic carcinomas (TC). TET are associated 4.9%. with autoimmune disorders (AID) in up to 30% of patients (pts). The Legal entity responsible for the study: RYTHMIC network/IFCT. pleura is the main metastatic site. Brain metastases are extremely Funding: Has not received any funding. infrequent for TET and they have been only described in case reports. Disclosure: All authors have declared no conflicts of interest. ABSTRACTS

TRAE—CRS—occurred early in the dosing cycle, did not recur, was SCLC typically mild in severity, and manageable. The maximum tolerated dose has not been reached. Dose-finding for monotherapy is ongoing. 48MO Clinical trial identification: NCT03319940. Phase I study of AMG 757, a delta-like ligand 3 (DLL3) Editorial acknowledgement: Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was targeting, half-life extended bispecific T-cell provided by Jacqueline Sayyah, PhD of Amgen Inc. and Sukanya engager immuno-oncology therapy, in small cell lung Raghuraman, PhD of Cactus Life Sciences, part of Cactus cancer (SCLC) Communications, and was funded by Amgen Inc. Legal entity responsible for the study: Amgen Inc. 1 2 3 4 5 L. Paz-Ares , T.K. Owonikoko , M. Johnson , R. Govindan , H. Izumi , Funding: Amgen Inc. 6 7 8 9 10 V. Lai , H. Borghaei , M. Boyer , R.J. Boosman , H-D. Hummel , Disclosure: L. Paz-Ares: Leadership role: Genomica; Leadership role: European 11 12 13 13 13 F. Blackhall , A. Dowlati , Y. Zhang , S. Mukherjee , B. Sable , Medicines Agency; Leadership role: ALTUM Sequencing; Travel/Accommodation/ A. Pati13, A. Shetty13, N. Hashemi Sadraei13, S. Champiat14 Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: 1CNIO-H12o Lung Cancer Unit, University Hospital 12 de Octubre, Madrid, AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; 2 Travel/Accommodation/Expenses: MBS; Advisory/Consultancy, Travel/ Spain; Department of Hematology and Medical Oncology, Emory Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Takeda; 3 University School of Medicine, Atlanta, GA, USA; Lung Cancer Research, Advisory/Consultancy: Novartis; Advisory/Consultancy: Ipsen; Advisory/ Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN, USA; Consultancy: Servier; Advisory/Consultancy: Sanofi; Advisory/Consultancy: 4Divisions of Hematology and Oncology, Washington University Medical Roche/Genetech; Advisory/Consultancy: Amgen; Advisory/Consultancy: Merck; 5 Advisory/Consultancy: Lilly; Advisory/Consultancy: Boehringer Ingelheim; School, St. Louis, MO, USA; Department of Thoracic Oncology, National Advisory/Consultancy: BMS; Advisory/Consultancy: Merck Serono; Advisory/ 6 Cancer Center Hospital East, Kashiwa, Japan; Thoracic Oncology Service, Consultancy: PharmaMar; Advisory/Consultancy: Celgene; Advisory/Consultancy: Department of Medicine, Division of Solid Tumor Oncology, Memorial Sysmex; Advisory/Consultancy: Incyte; Advisory/Consultancy: Bayer; Advisory/ Sloan Kettering Cancer Center, New York, NY, USA; 7Department of Consultancy: Advanced Accelerator Applications; Advisory/Consultancy: Blueprint Medicines. T.K. Owonikoko: Advisory/Consultancy, Research grant/ Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA; Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding 8 9 Chris O′Brien Lifehouse, Camperdown, Australia; The Netherlands (institution): Celgene; Advisory/Consultancy: Lilly; Advisory/Consultancy: Cancer Institute, Amsterdam, Netherlands; 10Comprehensive Cancer Sandoz; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research Center Mainfranken, University Hospital Würzburg, Würzburg, Germany; grant/Funding (institution): AbbVie; Advisory/Consultancy: Eisai; Advisory/ 11 Consultancy, Research grant/Funding (institution): G1 Therapeutics; Advisory/ Medical Oncology Department, The Christie NHS Foundation Trust, Consultancy: Takeda; Advisory/Consultancy: Seattle Genetics; Advisory/ 12 Manchester, UK; University Hospitals, Seidman Cancer and Case Western Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy: Reserve University, Cleveland, OH, USA; 13Amgen Inc., Thousand Oaks, CA, MedImmune; Advisory/Consultancy: BerGenBio; Advisory/Consultancy: Lilly; USA; 14Drug Development Department (DITEP), Gustave Roussy, Paris- Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/ Consultancy: AstraZeneca; Advisory/Consultancy: PharmaMar; Advisory/ Saclay University, Villejuif, France Consultancy: Boehringer Ingelheim; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Xcovery; Advisory/Consultancy, Research grant/Funding Background: AMG 757 simultaneously binds DLL3 on SCLC cells and (institution): Bayer; Advisory/Consultancy: Heron Pharmaceutical; Advisory/ CD3 on T cells leading to T cell- mediated tumor lysis. Data from an Consultancy: ARMO BioSciences; Shareholder/Stockholder/Stock options: ongoing phase I study of AMG 757 in SCLC are reported. Cambium Medical Technologies; Research grant/Funding (self): Stem CentRx; Methods: Safety and efficacy were evaluated in a phase I trial of Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): AstraZeneca/MedImmune; Research grant/Funding (institution): AMG 757 for patients (pts) with relapsed/refractory SCLC after >= 1 Corvus Pharmaceuticals; Research grant/Funding (institution): United platinum-based regimen (NCT03319940). AMG 757 was administered Therapeutics; Research grant/Funding (institution): Loxo/Lilly; Research grant/ intravenously (9 dose levels (DLs); dose range: 0.003−30 mg q2w, ± Funding (institution): Fujifilm; Research grant/Funding (institution): Pfizer; step dosing). Research grant/Funding (institution): Aeglea Biotherapeutics; Research grant/ − Funding (institution): Incyte; Research grant/Funding (institution): Merck; Results: As of 03 Nov 2020, 52 pts (median age, 64 [32 80] y; median Licensing/Royalties: Emory University School of Medicine, Atlanta, GA; prior lines of therapy, 2 [1−6]) were enrolled. 79% (41/52) of pts Honoraria (self), Received fees for non-CME/CE services : Roche/Genentech; reported treatment (tx)-related adverse events (TRAEs) (Grade [Gr] >= Honoraria (self), Received fees for non-CME/CE services: EMD Serono; Non- 2, 29/52 [56%], Gr >= 3, 12/52 [23%], Gr >= 4, 4/52 [8%]). TRAEs remunerated activity/ies: Reflexion Medical; Research grant/Funding (institution): Astellas Pharma. M. Johnson: Advisory/Consultancy: Otsuka; Advisory/ accounted for 1 tx discontinuation and 1 death (Gr 5 pneumonitis, DL, Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/ 0.3 mg). Cytokine release syndrome (CRS; 44%; Lee criteria (2014): Gr Consultancy, Research grant/Funding (institution), Travel/Accommodation/ 2, 5/52 [10%], Gr 3, 1/52 [2%], no Gr >= 4) was the most common Expenses: Boehringer Ingelheim; Advisory/Consultancy, Research grant/ TRAE and typically occurred in cycle 1. Median time to onset of CRS was Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/ − Consultancy: Calithera Biosciences; Advisory/Consultancy, Research grant/ 9(3 52) h following an AMG 757 dose; median duration was 60 Funding (institution), Travel/Accommodation/Expenses: Merck; Advisory/ (3−197) h. Fever (31%), tachycardia (19%), and nausea (14%) were the Consultancy, Research grant/Funding (institution): Loxo; Advisory/Consultancy: most common CRS-related symptoms. Significant increases in cytokine Sanofi; Advisory/Consultancy, Research grant/Funding (institution): Mirati (IL-8, MCP-1, IFN-g, IL-10, IL-6, MIP-1a, MIP-1b, TNF-a) levels from Therapeutics; Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas Pharma; Advisory/Consultancy, Research grant/Funding (institution), Travel/ baseline in the 24 h following the first AMG 757 dose in cycle 1 were Accommodation/Expenses: Pfizer; Advisory/Consultancy: Mersana; Advisory/ observed in pts experiencing CRS vs. pts who did not experience CRS Consultancy, Research grant/Funding (institution): BeiGene; Advisory/ symptoms. CRS did not result in tx discontinuation or deaths and was Consultancy, Research grant/Funding (institution), Travel/Accommodation/ managed with supportive care, corticosteroids, and/or anti-IL-6R. 14% Expenses: Incyte; Advisory/Consultancy, Research grant/Funding (institution): Guardant Health; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; (7/51) of pts achieved a confirmed partial response (PR) (modified Advisory/Consultancy, Research grant/Funding (institution): Ribon Therapeutics; RECIST 1.1) in 4 DLs (0.3 mg [8% of PR], 1 mg [13%], 3 mg [33%], and Advisory/Consultancy: Achilles Therapeutics; Advisory/Consultancy: Atreca; 10 mg [20%]). Stable disease was seen in 24% (12/51). Median time to Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; response was 1.8 months; the estimated duration of response was > 6 Advisory/Consultancy: Gristone Oncology; Advisory/Consultancy, Travel/ Accommodation/Expenses: Janssen Oncology; Advisory/Consultancy, Research months in 83% (95% CI: 27%, 98%) of pts with a confirmed PR. An grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Advisory/ unconfirmed PR was noted in an additional pt (30 mg DL). Consultancy: Association of Community Cancer Centers [ACCC]; Research grant/ Conclusions: AMG 757 showed an acceptable safety profile and Funding (institution), Travel/Accommodation/Expenses: AbbVie; Travel/ preliminary evidence for efficacy in pts with SCLC. The most common Accommodation/Expenses: Clovis Oncology; Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi Sankyo; Research grant/Funding

Journal of Thoracic Oncology Vol. 16 No. 4S: S720–S728 April 2021 Abstracts S721

(institution), Travel/Accommodation/Expenses: EMD Serono; Travel/ Advisory/Consultancy: Takeda; Advisory/Consultancy: Roche; Advisory/ Accommodation/Expenses: Exelixis; Travel/Accommodation/Expenses: Consultancy: Ipsen; Advisory/Consultancy: Cell Medica; Advisory/Consultancy: Genentech; Travel/Accommodation/Expenses: Sysmex; Travel/Accommodation/ MSD; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Expenses: Vapotherm; Research grant/Funding (institution), Travel/ Speaker Bureau/Expert testimony: Boehringer Ingelheim; Research grant/ Accommodation/Expenses: Novartis; Research grant/Funding (institution), Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Travel/Accommodation/Expenses: Sanofi; Research grant/Funding (institution): Research grant/Funding (institution): BMS; Research grant/Funding (institution): Kadmon; Research grant/Funding (institution): Janssen; Research grant/Funding Amgen. A. Dowlati: Advisory/Consultancy, Research grant/Funding (institution): (institution): Genmab; Research grant/Funding (institution): Stem CentRx; Takeda; Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Checkpoint Therapeutics; Research grant/ Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Funding (institution): Array BioPharma; Research grant/Funding (institution): Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BMS; Advisory/ Regeneron; Research grant/Funding (institution): Lycera; Research grant/Funding Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, (institution): Tarveda Therapeutics; Research grant/Funding (institution): Research grant/Funding (institution): Ipsen; Research grant/Funding (institu- CytomX Therapeutics; Research grant/Funding (institution): Dynavax; Research tion): Loxo; Research grant/Funding (institution): Incuron; Research grant/ grant/Funding (institution): Birdie; Research grant/Funding (institution): Corvus Funding (institution): Regeneron; Research grant/Funding (institution): Tesaro; Pharmaceuticals; Research grant/Funding (institution): Genocea Biosciences; Research grant/Funding (institution): Symphogen. Y. Zhang: Shareholder/ Research grant/Funding (institution): Gritstone Oncology; Research grant/ Stockholder/Stock options, Full/Part-time employment: Amgen Inc. Funding (institution): Amgen; Research grant/Funding (institution): S. Mukherjee: Shareholder/Stockholder/Stock options, Full/Part-time employ- Adaptimmune; Research grant/Funding (institution): Syndax; Research grant/ ment: Amgen Inc. B. Sable: Shareholder/Stockholder/Stock options, Full/Part- Funding (institution): Neovia Oncology; Research grant/Funding (institution): time employment: Amgen Inc. A. Pati: Shareholder/Stockholder/Stock options, Acerta Pharma; Research grant/Funding (institution): Takeda; Research grant/ Full/Part-time employment: Amgen Inc. A. Shetty: Shareholder/Stockholder/ Funding (institution): Shattuck Labs; Research grant/Funding (institution): Stock options, Full/Part-time employment: Amgen Inc. N. Hashemi Sadraei: Apexigen; Research grant/Funding (institution): Atreca; Research grant/Funding Shareholder/Stockholder/Stock options, Full/Part-time employment: Amgen Inc. (institution): OncoMed; Research grant/Funding (institution): Immunocore; S. Champiat: Honoraria (self), Advisory/Consultancy: Amgen Inc.; Honoraria Research grant/Funding (institution): Jounce Therapeutics; Research grant/ (self), Research grant/Funding (institution), Travel/Accommodation/Expenses, Funding (institution): University of Michigan; Research grant/Funding (institu- Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Research grant/ tion): WindMIL; Research grant/Funding (institution): TCR2 Therapeutics; Funding (institution): BMS; Honoraria (self): Janssen; Honoraria (self): Merck; Research grant/Funding (institution): Arcus Biosciences. R. Govindan: Advisory/ Honoraria (self), Travel/Accommodation/Expenses: MSD; Honoraria (self): Consultancy: GSK; Advisory/Consultancy: Genentech/Roche; Honoraria (self), Novartis; Honoraria (self), Research grant/Funding (institution), Travel/ Advisory/Consultancy: AbbVie; Advisory/Consultancy: Pfizer; Advisory/ Accommodation/Expenses, Non-remunerated activity/ies: Roche; Advisory/ Consultancy: AstraZeneca/MedImmune; Advisory/Consultancy: EMD Serono; Consultancy: AbbVie; Advisory/Consultancy: Adaptimmune; Advisory/ Advisory/Consultancy: Lilly; Advisory/Consultancy: Nektar; Advisory/ Consultancy: Aduro Biotech; Advisory/Consultancy: Agios Pharmaceuticals; Consultancy: Celgene; Advisory/Consultancy: BMS; Advisory/Consultancy: Advisory/Consultancy: Argen-X Bvba; Advisory/Consultancy: Arno Merck Serono; Advisory/Consultancy: Phillips Gilmore Oncology; Advisory/ Therapeutics; Advisory/Consultancy: Astex Pharmaceuticals; Advisory/ Consultancy: Ignyta; Advisory/Consultancy: Jounce Therapeutics; Advisory/ Consultancy: AstraZeneca Ab; Advisory/Consultancy: Aveo; Advisory/ Consultancy: Roche; Advisory/Consultancy: Janssen; Advisory/Consultancy: Consultancy: Basilea Pharmaceutica International Ltd; Advisory/Consultancy: Amgen; Advisory/Consultancy: Achilles Therapeutics; Advisory/Consultancy: Bayer Healthcare Ag; Advisory/Consultancy: Bbb Technologies Bv; Advisory/ Inivata; Honoraria (self): Genentech; Honoraria (self): Geneplus. V. Lai: Consultancy: Beigene; Advisory/Consultancy: Blueprint Medicines; Advisory/ Advisory/Consultancy: PharmaMar; Advisory/Consultancy: G1 Therapeutics; Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Jazz Boehringer Ingelheim; Advisory/Consultancy: Boston Pharmaceuticals; Advisory/ Pharmaceuticals; Research grant/Funding (institution): Amgen; Research grant/ Consultancy: Bristol Myers Squibb, Ca; Advisory/Consultancy: Celgene Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Corporation; Advisory/Consultancy: Chugai Pharmaceutical Co; Advisory/ AbbVie. H. Borghaei: Advisory/Consultancy, Research grant/Funding (institution), Consultancy: Clovis Oncology; Advisory/Consultancy: Cullinan-Apollo; Advisory/ Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Research grant/ Consultancy: Daiichi Sankyo; Advisory/Consultancy: Debiopharm; Advisory/ Funding (institution), Travel/Accommodation/Expenses: Lilly; Advisory/ Consultancy: Eisai; Advisory/Consultancy: Eisai Limited; Advisory/Consultancy: Consultancy, Travel/Accommodation/Expenses: Genentech; Advisory/ Eli Lilly; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Faron Consultancy, Research grant/Funding (institution): Celgene; Honoraria (self), Pharmaceuticals Ltd; Advisory/Consultancy: Forma Tharapeutics; Advisory/ Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding Consultancy: Gamamabs; Advisory/Consultancy: Genentech; Advisory/ (institution): Merck; Advisory/Consultancy, Travel/Accommodation/Expenses: Consultancy: Glaxosmithkline; Advisory/Consultancy: H3 Biomedicine; EMD-Serono; Advisory/Consultancy: Boehringer-Ingelheim; Advisory/ Advisory/Consultancy: Hoffmann La Roche Ag; Advisory/Consultancy: Imcheck Consultancy: AstraZeneca; Advisory/Consultancy: Novartis; Advisory/ Therapeutics; Advisory/Consultancy: Innate Pharma; Advisory/Consultancy: Consultancy: Genmab; Advisory/Consultancy: Regeneron; Advisory/ Institut De Recherche Pierre Fabre; Advisory/Consultancy: Iris Servier; Consultancy: BioNTech; Advisory/Consultancy: Cantargia AB; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Janssen Cilag; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/ Advisory/Consultancy: Janssen Research Foundation; Advisory/Consultancy: Consultancy: AbbVie; Advisory/Consultancy: Axiom; Advisory/Consultancy: Kura Oncology; Advisory/Consultancy: Kyowa Kirin Pharm. Dev; Advisory/ PharmaMar; Advisory/Consultancy, Officer/Board of Directors, Data and Safety Consultancy: Lilly France; Advisory/Consultancy: Loxo Oncology; Advisory/ Monitoring Board: Takeda; Advisory/Consultancy: HUYA Bioscience Consultancy: Lytix Biopharma As; Advisory/Consultancy, Non-remunerated International; Advisory/Consultancy: GLG; Honoraria (self), Advisory/ activity/ies: Medimmune; Advisory/Consultancy: Menarini Ricerche; Advisory/ Consultancy: Daiichi; Research grant/Funding (institution): Millenium; Officer/ Consultancy: Merck Sharp & Dohme Chibret; Advisory/Consultancy: Merrimack Board of Directors, Data and Safety Monitoring Board: University of Pennsylvania Pharmaceuticals; Advisory/Consultancy: Merus; Advisory/Consultancy: [CAR T Progam; Officer/Board of Directors, Data and Safety Monitoring Board: Millennium Pharmaceuticals; Advisory/Consultancy: Molecular Partners Ag; Incyte; Travel/Accommodation/Expenses: Lilly; Advisory/Consultancy, Advisory/Consultancy: Nanobiotix; Advisory/Consultancy: Nektar Therapeutics; Shareholder/Stockholder/Stock options: Sonnetbio; Advisory/Consultancy, Advisory/Consultancy: Novartis Pharma; Advisory/Consultancy: Octimet Shareholder/Stockholder/Stock options: Rgenix. M. Boyer: Honoraria (self), Oncology Nv; Advisory/Consultancy: Oncoethix; Advisory/Consultancy: Advisory/Consultancy, Research grant/Funding (institution), Travel/ Oncopeptides; Advisory/Consultancy: Orion Pharma; Advisory/Consultancy: Ose Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Pharma; Advisory/Consultancy, Research grant/Funding (institution), Non- Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: BMS; remunerated activity/ies: Pfizer; Advisory/Consultancy: Pharma Mar; Advisory/ Advisory/Consultancy: Janssen; Honoraria (self), Research grant/Funding (insti- Consultancy: Pierre Fabre; Advisory/Consultancy: Medicament; Advisory/ tution), Travel/Accommodation/Expenses: Genentech/Roche; Honoraria (self), Consultancy: Sanofi Aventis; Advisory/Consultancy: Seattle Genetics; Advisory/ Research grant/Funding (institution): Boehringer Ingelheim; Research grant/ Consultancy: Sotio A.S; Advisory/Consultancy: Syros Pharmaceuticals; Advisory/ Funding (institution): Pfizer; Research grant/Funding (institution): Lilly; Research Consultancy: Taiho Pharma; Advisory/Consultancy: Tesaro; Advisory/ grant/Funding (institution): Amgen; Research grant/Funding (institution): Consultancy: Xencor; Research grant/Funding (institution), Non-remunerated BeiGene; Research grant/Funding (institution): Ascentage Pharma; Research activity/ies: Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Benitec Biopharma; Research grant/Funding (insti- grant/Funding (institution): Onxeo; Research grant/Funding (institution): Sanofi; tution): Novartis. H-D. Hummel: Travel/Accommodation/Expenses: Janssen-Cilag; Non-remunerated activity/ies: Bayer; Non-remunerated activity/ies: MBS; Non- Travel/Accommodation/Expenses: Boehringer Ingelheim; Travel/ remunerated activity/ies: Johnson & Johnson; Non-remunerated activity/ies: Lilly; Accommodation/Expenses: Amgen. F. Blackhall: Advisory/Consultancy: Non-remunerated activity/ies: NH TherAGuiX. All other authors have declared no Regeneron; Advisory/Consultancy: Medivatin; Advisory/Consultancy: AbbVie; conflicts of interest. S722 Journal of Thoracic Oncology Vol. 16 No. 4S

49MO 50P Patterns of relapse following thoracic radiotherapy in patients A phase Ib study of CC-90011, a potent, reversible, oral LSD1 with limited-stage small cell lung cancer as part of the inhibitor, plus etoposide and cisplatin (EP) or carboplatin (EC) CONVERT trial in patients (Pts) with first-line (1L) extensive-stage (ES) small cell lung cancer (SCLC): Updated results R. Portner1, E. Vasquez Osorio2, R. Iype1, C. Faivre-Finn1 1Clinical Oncology Department, The Christie NHS Foundation Trust, Manchester, S. Ponce Aix1, O. Juan-Vidal2, E. Carcereny3, J.M. Trigo4, UK; 2Division of Cancer Sciences, University of Manchester, Manchester, UK M. Provencio5, L. Greillier6, A. Navarro7, J. Bennouna8, A. Santoro9, R. Berardi10, B. Besse11, H. Gonzalez12, J. de Alvaro12, Background: Small-cell lung cancer (SCLC) is an aggressive disease J.L. Parra-Palau12,T.Sánchez-Pérez12, I. Aronchik13, E. Filvaroff13, associated with poor prognosis despite curative-intent treatment. M. Lamba13, Z. Nikolova12, L. Paz-Ares1 1Hospital Universitario 12 de Recurrences within high-dose radiotherapy field can indicate radio- Octubre, H120-CNIO Lung Cancer Unit, Universidad Complutense and resistance. We aim to identify areas of relapse and whether they Ciberonc, Madrid, Spain; 2Hospital Universitari i Politecnic̀ La Fe, Valencia, occurred within high-dose areas. Spain; 3Institut Catalàd’Oncologia Badalona-Hospital Germans Trias i Methods: Patients with limited-stage SCLC treated at The Christie as Pujol, Badalona, Spain; 4Hospital Clınicó Universitario Virgen de la part of the phase III CONVERT trial from 2008 were included in the Victoria, Malaga,́ Spain; 5Universidad Autonomá de Madrid, Instituto de analysis. Patients received either 45 Gy in 30 twice-daily (BD) fractions Investigacioń Puerta de Hierro, Hospital Puerta de Hierro de or 66 Gy in 33 daily (OD) fractions with concurrent chemotherapy. Majadahonda, Majadahonda, Spain; 6Aix Marseille University, APHM, Elective nodal irradiation was not given. All follow-up CT scans were Marseille, France; 7Hospital Universitari Vall d’Hebron, Barcelona, Spain; retrospectively reviewed for evidence of relapse. Patients were classified 8Thoracic Oncology Unit, University Hospital of Nantes, Nantes, France; as thoracic-only relapses (i.e. within radiotherapy field), distant 9Humanitas Clinical and Research Center, IRCCS, Humanitas University, metastases or relapse in both areas. For thoracic relapses all lesions Department of Biomedical Sciences, Rozzano-Milan, Italy; 10Università that progressed were contoured on the relapse CT by a radiation Politecnica Marche, AOU Ospedali Riuniti, Ancona, Italy; 11Gustave Roussy oncologist. We estimated the planned mean dose over each relapse Cancer Campus, Villejuif, France; 12Centre for Innovation and lesions by mapping the planning dose from the planning CT onto the Translational Research Europe, A Bristol Myers Squibb Company, Seville, relapse CT using non-rigid registrations (Elastix). As extreme anatomical Spain; 13Bristol Myers Squibb, Princeton, NJ, USA changes existed for some patients, registration was repeated using NiftyReg. Lesions that resulted in disagreement of 2 Gy were visually Background: ES SCLC is an aggressive disease with relapses despite checked and manually tuned. initial response to chemotherapy. In the CC-90011-SCLC-001 study, CC- Results: 49 of 90 patients had evidence of relapse. 20 patients had 90011 in combination with EP was well-tolerated in 1L ES SCLC pts. thoracic-only relapses, 19 had only distant metastases and 10 patients Here, we report updated data for CC-90011 + EP and results with CC- relapsed in both areas. Of the 30 thoracic relapses 25 sets of scans were 90011 + EC. available for mapping analysis. We identified 67 lesions in total, a mean Methods: CC-90011-SCLC-001 (NCT03850067) is a phase Ib study of of 2.7 lesions per patient (range 1–9). Mean size of lesions was 18.8 cm3 CC-90011 + EP and CC-90011 + EC in 1L ES SCLC. In the chemotherapy (range 0.01 cm3–549 cm3). 16 of 25 patients relapsed within 95% phase, pts received EP or EC + escalating doses of CC–90011 (20, 40, isodose region (11/25 received BD radiotherapy) and 6 also had distant 60 mg) on days 1 and 8 of a 21-d cycle for 4–6 cycles. Responders metastases. The remaining 9 of 25 thoracic relapses progressed within entered a maintenance phase and received CC-90011 60 mg once/wk in 20% to 95% isodoses (6/9 received OD radiotherapy). a 28-d cycle. Primary endpoints were safety, tolerability, and recom- Conclusions: 3 out of 4 patients who relapsed had thoracic progression. mended phase II dose (RP2D). Other endpoints were efficacy (RECIST The mapping analysis showed that the majority of thoracic relapses 1.1 criteria), pharmacokinetics (PK), and pharmacodynamics (PD). (64.0%) occurred within the high-dose radiotherapy region. This Results: As of 11 Sept 2020, 19 pts received CC-90011 at 20 (n = 8), 40 suggest that there is scope for further local treatment intensification. (n = 7), and 60 mg (n = 4) + EP and 5 received CC-90011 at 20 (n = 3) Clinical trial identification: 06_DOG07_68 ISRCTN91927162 and 40 mg (n = 2) + EC. Of the 19 pts (CC-90011 + EP) and 5 pts (CC- CONVERT Trial protocol: Version 3, 10JUN2008. 90011 + EC), 12 and 3 received CC-90011 maintenance for a median of Legal entity responsible for the study: Corinne Faivre-Finn. 7.5 and 4.0 wk; 6 and 1 pts discontinued treatment due to adverse Funding: Has not received any funding. events (AEs; n = 4), withdrawal by patient (n = 1), or progressive Disclosure: All authors have declared no conflicts of interest. disease (n = 2). The RP2D of CC-90011 was established as 40 mg with EP and the evaluation of the RP2D of CC-90011 with EC is ongoing. Four pts had dose-limiting toxicity, 1 with grade 3 neutropenia at CC-90011 20 mg + EP, 2 with grade 2–4 thrombocytopenia or grade 4 neutropenia/ febrile neutropenia at CC-90011 60 mg + EP, and 1 with grade 4 thrombocytopenia at CC-90011 40 mg + EC. The most common grade 3/ 4 AEs were neutropenia (63%) and thrombocytopenia (42%) with CC- 90011 + EP, and thrombocytopenia (80%) and neutropenia (40%) with CC-90011 + EC. All 19 efficacy-evaluable pts achieved a partial response. PK profiles of the combinations were consistent with CC-90011 monotherapy. MMD expression decreased ≥50% at CC-90011 20 mg and 40 mg + EP and CC-90011 20 mg + EC in available samples. Conclusions: CC-90011 + EP/EC is well tolerated in 1L ES SCLC with no new safety signals. The study is ongoing to further evaluate CC-90011 + EP/EC with nivolumab. Clinical trial identification: NCT03850067; EudraCT: 2018-002799-42. Editorial acknowledgement: This study was supported by Celgene, a Bristol Myers Squibb Company, with special thanks for the work performed by Li Li from Bristol Myers Squibb. Writing and editorial April 2021 Abstracts S723 assistance were provided by Hannah Chang, PhD, of Bio Connections Perez:́ Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock LLC, funded by Bristol Myers Squibb Company. options, Full/Part-time employment: Celgene - Bristol Myers Squibb Company. I. Aronchik: Shareholder/Stockholder/Stock options, Full/Part-time employment: Legal entity responsible for the study: Celgene, a Bristol Myers Squibb BMS. E. Filvaroff: Travel/Accommodation/Expenses, Shareholder/Stockholder/ Company. Stock options, Licensing/Royalties, Full/Part-time employment: BMS; Funding: Celgene, a Bristol Myers Squibb Company. Shareholder/Stockholder/Stock options: Amgen; Shareholder/Stockholder/ Disclosure: S. Ponce Aix: Advisory/Consultancy, Speaker Bureau/Expert Stock options: Gilead; Shareholder/Stockholder/Stock options: Genentech/Roche. testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; M. Lamba: Research grant/Funding (self), Shareholder/Stockholder/Stockoptions, Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/ Full/Part-time employment: Pfizer; Research grant/Funding (self), Shareholder/ Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/ Stockholder/Stock options, Full/Part-time employment: Celgene (now part of Expert testimony: Takeda. O. Juan-Vidal: Honoraria (self), Advisory/Consultancy: Bristol Myers Squibb); Research grant/Funding (self), Shareholder/Stockholder/ Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Bristol-Myers Stock options, Full/Part-time employment: Bristol Myers Squibb. Z. Nikolova: Squibb; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme; Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/ Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Part-time employment: Celgene, A Bristol-Myers Squibb Company. L. Paz-Ares: Roche/Genetech; Honoraria (self), Advisory/Consultancy: AstraZeneca; Leadership role: ALTUM Sequencing; Leadership role: Genomica; Honoraria (self): Advisory/Consultancy: Pfizer; Advisory/Consultancy: Eli Lilly; Advisory/ Adacap; Honoraria (self): Amgen; Honoraria (self), Research grant/Funding (self): Consultancy: AbbVie; Honoraria (self): Takeda; Travel/Accommodation/ AstraZeneca; Honoraria (self): Bayer; Honoraria (self): Blueprint Medicines; Expenses: MSD. E. Carcereny: Advisory/Consultancy, Travel/Accommodation/ Honoraria (self): Boehringer Ingelheim; Honoraria (self), Research grant/Funding Expenses: Takeda; Advisory/Consultancy, Travel/Accommodation/Expenses: (self): Bristol-Myers Squibb; Honoraria (self): Celgene; Honoraria (self): Eli Lilly; Roche; Travel/Accommodation/Expenses: MSD; Advisory/Consultancy: BMS. J. Honoraria (self): Incyte; Honoraria (self): Ipsen; Honoraria (self): Merck; M. Trigo: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/ Honoraria (self), Research grant/Funding (self): Merck Sharp and Dohme; Accommodation/Expenses: MSD; Speaker Bureau/Expert testimony, Travel/ Honoraria (self): Novartis; Honoraria (self), Research grant/Funding (self): Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony: Eisai; Pfizer; Honoraria (self): Pharmamar; Honoraria (self): Roche; Honoraria (self): Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Sanofi; Honoraria (self): Servier; Honoraria (self): Sysmex; Honoraria (self): Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/ Takeda. All other authors have declared no conflicts of interest. Accommodation/Expenses: BMS; Advisory/Consultancy: Bayer; Advisory/ Consultancy: Boehringer; Advisory/Consultancy: Takeda; Advisory/Consultancy: GSK. L. Greillier: Research grant/Funding (institution): Celgene; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): BMS; Honoraria 51P (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/ Liver kinase B1 (LKB1) and phosphorylated AMP kinase (AMPK) Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; expression in small cell lung cancer (SCLC): Association with Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Honoraria prognosis and tumour immune microenvironment (TIME) (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; features Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Sanofi; Advisory/Consultancy, Research grant/Funding (institution): 1 2 3 4 4 Takeda; Honoraria (self), Research grant/Funding (institution): Pfizer; L. Bonanno , A. Dal Maso , A. Pavan , E. Zulato , G. Esposito , Honoraria (self), Travel/Accommodation/Expenses: Boehringer. A. Navarro: M. Fassan5, G. Nardo4, G. Pasello2, V. Guarneri2, F. Calabrese6, Speaker Bureau/Expert testimony: Oryzon Genomics; Advisory/Consultancy, F. Rea6, S. Indraccolo4, P.F. Conte2 1Oncologia 2, Istituto Oncologico Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/ 2 Accommodation/Expenses: Boehringer Ingelheim; Speaker Bureau/Expert testi- Veneto IOV - IRCCS, Padua, Italy; Dipartimento di Scienze Chirurgiche, mony, Travel/Accommodation/Expenses: Roche. J. Bennouna: Honoraria (self), Oncologiche e Gastroenterologiche, Universitàdegli Studi di Padova, Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Padua, Italy; 3Oncologia Medica, AULSS 3 Serenissima, Mestre, Italy; Advisory/Consultancy, Research grant/Funding (institution), Travel/ 4Immunologia e Diagnostica Molecolare Oncologica, Istituto Oncologico Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/ 5 ̀ Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Veneto IOV - IRCCS, Padua, Italy; Dipartimento di Medicina, Universita 6 Advisory/Consultancy: MSD; Honoraria (self): Boehringer-Ingelheim; Honoraria degli Studi di Padova, Padua, Italy; Dipartimento di Scienze Cardio- (self): Servier; Honoraria (self): Bayer. A. Santoro: Speaker Bureau/Expert Toraco-Vascolari e SanitàPubblica, Universitàdegli Studi di Padova, testimony: Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony: Padua, Italy BMS; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: AbbVie; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert Background: SCLC is characterised by high metastatic potential and testimony: Celgene; Speaker Bureau/Expert testimony: Servier; Advisory/ Consultancy, Speaker Bureau/Expert testimony: Gilead; Speaker Bureau/Expert dismal prognosis. LKB1 is a cell metabolism regulator and oncosup- testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testi- pressor. LKB1 downregulation has been associated with a cold TIME. mony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Arqule; LKB1 activates its main effector AMPK by phosphorylation. We aimed to Speaker Bureau/Expert testimony: Lilly; Speaker Bureau/Expert testimony: analyse the role of LKB1 in SCLC in relationship to TIME and its Sandoz; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker association with prognosis. Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert Methods: We retrospectively evaluated all SCLCs consecutively treated testimony: MSD; Advisory/Consultancy: Sanofi. R. Berardi: Advisory/Consultancy: at Istituto Oncologico Veneto and with available tissue from 1996 to MSD; Advisory/Consultancy: Boehringer; Advisory/Consultancy: Ostura; 2015. LKB1, pAMPK, PD-L1 (22C3) on tumor cells (TC) and on tumor Advisory/Consultancy: Lilly. B. Besse: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding immune-infiltrating cells (TIIC), CD8 and FOXP3 were evaluated by (institution): AstraZeneca; Research grant/Funding (institution): BeiGene; immunohistochemistry (IHC). Semiquantitative scores were used to Research grant/Funding (institution): Blueprint Medicines; Research grant/ handle IHC results as categorical variables. Primary objectives were to Funding (institution): BMS; Research grant/Funding (institution): Boehringer assess the impact of LKB1 expression on overall survival (OS) and the Ingelheim; Research grant/Funding (institution): Celgene; Research grant/ Funding (institution): Cristal Therapeutics; Research grant/Funding (institution): association with TIME components. Daiichi-Sankyo; Research grant/Funding (institution): Eli Lilly; Research grant/ Results: 71 cases were included: 45 (63.4%) received surgery,10 (14.1%) Funding (institution): GSK; Research grant/Funding (institution): Ignyta; Research radical chemoradiotherapy, 16 (22.5%) chemotherapy. LKB1 IHC was grant/Funding (institution): Ipsen; Research grant/Funding (institution): Inivata; positive in 63 (88.7%) SCLCs. LKB1 was highly positive (score > 3) in 55 Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Merck KGaA; Research grant/Funding (institution): MSD; Research grant/ (77.4%) cases. pAMPK was expressed in 38(54.3%) out of 70cases: 25/54 Funding (institution): Nektar; Research grant/Funding (institution): Onxeo; (46.3%) in LD SCLCs vs. 13/16 (81.3%) in extended SCLCs (p = 0.021). Research grant/Funding (institution): OSE immunotherapeutics; Research LKB1 score > 3 was associated with pAMPK expression (p = 0.047). LKB1 grant/Funding (institution): Pfizer; Research grant/Funding (institution): expression was significantly associated with a prolonged OS in the entire Pharma Mar; Research grant/Funding (institution): Roche-Genentech; Research – grant/Funding (institution): Sanofi; Research grant/Funding (institution): Servier; study population (median OS [mOS] 53.2 months [m], 95% CI: 20.8 72.4 Research grant/Funding (institution): Spectrum Pharmaceuticals; Research grant/ vs. 21.9 m, 95% CI 1.6–not calculable [NC], p = 0.017; hazard ratio [HR] Funding (institution): Takeda; Research grant/Funding (institution): Tiziana 0.40, 95% CI 0.18–0.87, p = 0.021) and in patients with LD-SCLCs (N = 55; Pharma; Research grant/Funding (institution): Tolero Pharmaceuticals. J.L. mOS 65.7 m, 95% CI 44.5–107.1 vs. 27.4 m, 95% CI 16.3–NC,p=0.013;HR Parra-Palau: Honoraria (self), Travel/Accommodation/Expenses, Shareholder/ – Stockholder/Stock options, Full/Part-time employment: Celgene/BMS. T. Sanchez-́ 0.31, 95% CI 0.11 0.82, p = 0.019). No significant association was found S724 Journal of Thoracic Oncology Vol. 16 No. 4S between LKB1 and TIME; pAMPK was significantly associated with absent Methods: We retrospectively identified patients with extended SCLC in PD-L1expressiononTC(p=0.040)andTIIC(p=0.016). which a Next Generation Sequencing (NGS) test was performed. Clinical Conclusions: LKB1/pAMPK deregulation may be associated with characteristics and treatment outcomes were described. The statistical metastatic stage and lack of LKB1 expression warrants further validation analysis was carried out with Stata15®. as poor prognostic marker. Studies on a validation cohort of metastatic Results: 1745 patients with lung carcinoma were analyzed. A tissue NGS SCLC are ongoing while DNA genotyping of LKB1 is planned in LD. was performed only in 15 out of 232 SCLC patients. Clinical Legal entity responsible for the study: Istituto Oncologico Veneto – characteristics of these were: median age 64 years, 53% male, 80% IRCCS. stage IV, 53,3% four or more metastatic localizations (liver (53,3%), CNS Funding: Has not received any funding. (40%)). ECOG 1, 69,2% and 0, 30,8% of patients. All patients received Disclosure: All authors have declared no conflicts of interest. standard first-line chemotherapy. The median progression free survival (PFS) was 7 months, the median number of treatment lines was 2 and the median overall survival was 22 months. Molecular findings are 52P described in the table. Most frequent alterations were mutations in RB1 Genetic and clinical profiling of a cohort of extended small and TP53. A third of patients (33%) had tumor mutational burden over 10 muts/Mb. One patient showed a pathogenic RET mutation but the cell lung carcinoma PFS with a targeted treatment as third line was only 40 days. Conclusions: Our cohort achieved longer survival than expected for E.M. Vida Navas1, J. Chamorro Pérez1, E. Corral de la Fuente1, advanced SCLC patients, although we only found one patient with a Y. Lage1,A.Gómez Rueda1, J. Torres Jiménez1, L. Sanz Gómez1, mutation suitable for targeted therapy. Further investigations are J.J. Soto Castillo1, P. Álvarez Ballesteros1, J. Esteban Villarrubia1, needed to understand the complexity of these tumors and the best V. Albarrán Fernández1, D.I. Rosero Rodrıgueź 1, M. San Román Gil1, therapeutic approaches for the different subgroups. J. Pozas Pérez1, M. Lario1, A. Caminoa Lizarralde2, Legal entity responsible for the study: The authors. P. Garrido Lopez1, M.E. Olmedo Garcıá1 1Medical Oncology Funding: Has not received any funding. Department, Hospital Universitario Ramon y Cajal, Madrid, Spain; Disclosure: All authors have declared no conflicts of interest. 2Pathology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain

Background: Small cell lung carcinoma (SCLC) is an extremely 53P aggressive malignancy with poor prognosis. Recently, there have been Antitumoral effects of the Met inhibitor savolitinib in improvements in identifying molecular subgroups and genetic pathways combination with durvalumab in a syngeneic small cell involved in the carcinogenesis of these tumors, but more effective lung cancer mouse model therapies are needed. Table 52P: Pathogenic mutations R. Del Rey-Vergara1, M.A. Galindo-Campos1, M. Hardy-Werbin1, L. Moliner2,A.Rıos-Hoyó 2, C. Martıneź 3, M. Carpes3, Pathogenic S. González-Gallardo1, Á. Taus2, A. Rovira1, E. Arriola2 1Cancer mutations Frequency Percentage Research Programme, IMIM - Institut Hospital del Mar d’Investigacions RB1 15 100 Mediques, Barcelona, Spain; 2Hospital del Mar, Barcelona, Spain; TP53 13 86,7 3Experimental Pathology Unit, IMIB-LAIB-Arrixaca, Murcia, Spain MYCL1 3 20 CREBBP 2 13,3 Background: Small cell lung cancer (SCLC) accounts for 15% of total RICTOR 2 13,3 lung cancers and its 5-years overall survival is less than 10%. Recently, PI3KCA 2 13,3 addition of anti-programmed death-ligand 1 (PD-L1) agents to ARID1A 2 13,3 chemotherapy has demonstrated marginally improved outcomes. The BAP1 1 6,6 hepatocyte growth factor (HGF)/Met pathway activation is associated TET2 1 6,6 RET 1 6,6 with chemo- and immune therapy resistance, and a worse prognosis in CDK12 1 6,6 cancer. The aim of this study was to test the antitumoral effect of FGF10 1 6,6 combining Met inhibition (savolitinib) with an anti-PD-L1 agent AKT1 1 6,6 (durvalumab) in SCLC. NOTCH1 1 6,6 Methods: Expression of the targets of interest (Met and PD-L1) was BARD1 1 6,6 determined by flow cytometry in the mouse KP1 SCLC cell line (Park K BRD4 1 6,6 et al. Nature Medicine 2011). B16-F10 (Met exon 14 mutated) mouse EP300 1 6,6 melanoma cell line was used as positive control for expression. KP1 and NF1 1 6,6 B16-F10 cells were subcutaneously injected in B6129SF1/J and FBXW7 1 6,6 FH 1 6,6 C57BL6/J mice, respectively. They were randomised into four groups – – NKX2-1 1 6,6 (SCLC n = 7; melanoma n = 6 per group) and treated starting day-3 CSF3R 1 6,6 post-cell implantation with vehicle and isotype IgG (control group), MPL 1 6,6 savolitinib (30 mg/kg P.O. 5 days/week), durvalumab (10 mg/kg I.P. NTRK1 1 6,6 twice a week) or a combination of both compounds. Tumour growth was CRKL 1 6,6 followed-up twice a week. NOTCH2 1 6,6 Results: KP1 cells showed low and no expression of Met and PD-L1, FAM123 1 6,6 respectively, whereas B16-F10 cells showed high levels of both proteins INPP4B 1 6,6 in vitro. In in vivo models, tumour growth was significantly reduced (p < CDKN2A 1 6,6 0.05) by savolitinib plus durvalumab compared to the control after 18 IRS2 1 6,6 3 PDCD1LG2 1 6,6 days or 14 days of treatment in both KP1 (714.74 ± 124.35 mm vs. 418.17 3 3 JAK2 1 6,6 ±153.73mm ) and B16-F10 (1295.31 ± 893.39 mm vs. 494.95 ± 3 C274 1 6,6 156.08 mm ) syngeneic models, respectively. Moreover, we observed MYCN 1 6,6 little effect of each drug alone in both Met mutant and wild-type models. April 2021 Abstracts S725

Conclusions: Our results show that combinatorial treatment with Methods: Newly diagnosed patients in the years 2010–2017 were savolitinib plus durvalumab provides a significantly more effective identified from the records of the Thoraxklinik Heidelberg and antitumor effect than each agent alone and warrants further studies in retrospectively analysed. SCLC. We hypothesize that this greater effect might be due to the Results: Among 1189 primary patients, two-thirds (63%, n = 755) modulation of certain functional immune cell subsets. Currently, presented with extensive (ED), and 37% (n = 434) with limited disease immune infiltrates in both tumour models are being evaluated. (LD). For most ED-SCLC patients (66%, n = 496), first-line chemother- Legal entity responsible for the study: FundacióIMIM. apy consisted exclusively of PE, 27% received other chemotherapies, Funding: Instituto de Salud Carlos III (PI19/00003). mainly vincristine-etoposide, upfront or after switch in subsequent Disclosure: Á. Taus: Honoraria (self), Advisory/Consultancy, Speaker Bureau/ treatment cycles due to clinical deterioration, while 7% forewent Expert testimony, Travel/Accommodation/Expenses: Boehringer-Ingelheim; systemic treatment altogether. The full course of 6 PE cycles was given to Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, 47% of ED patients, with an average number of cycles per patient 4.6, a Speaker Bureau/Expert testimony: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Honoraria (self), Advisory/Consultancy, median duration of treatment 3.5 months, and a median progression- Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; free survival of 5.8 months. In LD-SCLC, PE was used for 79% of patients Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: exclusively, and for 16% along with other chemotherapeutics, while 5% Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: of patients did not receive systemic treatment. Relapse or progression AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Tesaro-GSK. E. Arriola: Honoraria (self), Advisory/Consultancy, occurred in 80% of LD patients, in 27% already within the same year of Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/ initial diagnosis. Median overall survival (mOS) was 9.9 months for PE- Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, treated ED and 20.4 months for PE-treated LD-SCLC patients, with a 5- Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; year OS rate of 1% and 21%, respectively. Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/ Conclusions: PE is the first-line systemic treatment for approximately Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), two-thirds of ED and 80% of LD SCLC patients, but has limited activity, Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ with mOS below 1 year and long-term benefit in only about 20% of cases, Funding (self): Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/ respectively. Besides highlighting the need for novel therapeutic Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, strategies, these results define the size of the target population and Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, the efficacy threshold for promising add-on drugs in the routine setting. Speaker Bureau/Expert testimony: Takeda. All other authors have declared no Legal entity responsible for the study: Thoraxklinik Heidelberg conflicts of interest. gGmbH. Funding: Has not received any funding. Disclosure: F. Bozorgmehr: Honoraria (self), Research grant/Funding (self): 54P BMS; Honoraria (self): MSD. R. Elshafie: Honoraria (self), Research grant/Funding Determining the utilization and clinical impact of (self): Accuray; Honoraria (self): AstraZeneca; Honoraria (self): BMS; Honoraria (self): Novocure; Honoraria (self): Merck; Honoraria (self): Takeda. J. Kuon: platinum-etoposide for treatment of small cell lung Honoraria (self), Research grant/Funding (institution): AstraZeneca; Research cancer in the routine setting grant/Funding (self): Celgene. C-P. Heussel: Honoraria (self): Novartis; Honoraria (self): Basilea; Honoraria (self): AstraZeneca; Shareholder/Stockholder/Stock K. Dimitriou1, F. Bozorgmehr1, S. Liersch2, R. Elshafie3, J. Kuon1, options: GSK. F. Herth: Honoraria (self), Research grant/Funding (self): 4 4 5 6 7 AstraZeneca; Honoraria (self), Research grant/Funding (self): Roche; Honoraria L-A. Dinges , T. Eichkorn , C-P. Heussel , F. Eichhorn , H. Winter , (self), Research grant/Funding (self): Novartis. A. Stenzinger: Honoraria (self), 8 9 1 10 11 M. Schneider , F. Herth , M. Steins , A. Stenzinger , M. Thomas , Research grant/Funding (self): AstraZeneca; Honoraria (self), Research grant/ P. Christopoulos11 1Oncology Dept., Thoraxklinik Heidelberg, Funding (self): BMS; Honoraria (self), Research grant/Funding (self): Novartis; Heidelberg, Germany; 2Pharmacy Dept., Thoraxklinik Heidelberg, Honoraria (self), Research grant/Funding (self): Thermo Fisher; Research grant/ 3 Funding (self): Chugai; Research grant/Funding (self): Illumina. M. Thomas: Heidelberg, Germany; Radiation Oncology, Heidelberg University Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self), Hospital and Translational Research Center Heidelberg, Member of the Research grant/Funding (self): AstraZeneca; Honoraria (self), Research grant/ German Center for Lung Research (DZL), Heidelberg, Germany; 4Radiation Funding (self): Roche; Honoraria (self), Research grant/Funding (self): Takeda; Oncology, Heidelberg University Hospital, Heidelberg, Germany; Honoraria (self), Research grant/Funding (self): Novartis. P. Christopoulos: 5 Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria Radiology Dept., Thoraxklinik Heidelberg and Translational Research (self), Research grant/Funding (institution): Roche; Honoraria (self), Research Center Heidelberg, Member of The German Center for Lung Research grant/Funding (self): Takeda; Honoraria (self): Pfizer; Honoraria (self): (DZL), Heidelberg, Germany; 6Surgery Dept., Thoraxklinik Heidelberg, Boehringer; Honoraria (self), Research grant/Funding (self): Novartis. All other Heidelberg, Germany; 7Surgery Dept., Thoraxklinik Heidelberg and authors have declared no conflicts of interest. Translational Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, Germany; 8Translational Research Unit, Thoraxklinik Heidelberg and Translational Research Center 55P Heidelberg, Member of the German Center for Lung Research (DZL), Assessment of cardiovascular biomarkers for individualised Heidelberg, Germany; 9Pneumology Dept., Thoraxklinik Heidelberg and treatment decision in small cell lung cancer (SCLC) Translational Research Center Heidelberg, Member of the German Center 10 for Lung Research (DZL), Heidelberg, Germany; Pathology, Heidelberg E. Gezelius1, P-O. Bendahl2, W. Gallo3, K. Goncalves de Oliveira2, University Hospital and Translational Research Center Heidelberg, L. Ek4, B. Bergman5, J. Sundberg6, O. Melander3, M. Belting1 Member of the German Center for Lung Research (DZL), Heidelberg, 1Department of Clinical Sciences Lund, Lund University - Faculty of 11 Germany; Oncology Dept., Thoraxklinik Heidelberg and Translational Medicine, Lund, Sweden; 2Lund University - Faculty of Medicine, Lund, Research Center Heidelberg, Member of the German Center for Lung Sweden; 3Lund University - Faculty of Medicine, Malmo, Sweden; Research (DZL), Heidelberg, Germany 4Department of Respiratory Medicine, Skåne University Hospital, Lund, Sweden; 5Department of Respiratory Medicine, Sahlgrenska University Background: Small-cell lung cancer (SCLC) accounts for 15% of Hospital, Gothenburg, Sweden; 6Department of Hematology, Radiophysics pulmonary malignancies and is an aggressive disease with only little therapeutic progress in the last years. Aim of the current study is to and Oncology, Skåne University Hospital, Lund, Sweden characterize the utilization of platinum-etoposide (PE) chemotherapy in Background: Comorbidity is increasingly common in SCLC and may real-world SCLC management, as a basis for the predicting the potential significantly affect treatment tolerability and patient outcome. penetration, and benchmark for assessing the clinical benefit of novel Cardiopulmonary comorbidity thus needs to be carefully considered drugs in combination therapies. when making treatment choices. However, cardiopulmonary stress can S726 Journal of Thoracic Oncology Vol. 16 No. 4S be challenging to evaluate clinically in these patients, which warrants inhalation history. After PSM, smoking status made no statistical biomarkers as a tool for objective assessment and individualised difference on PFS(p = 0.163) and OS(p = 0.983). However, patients treatment decision. Here, we have investigated circulating levels of the with long-time second-hand smoking history had worse PFS (No vs. vasoactive peptides adrenomedullin (ADM), atrial natriuretic peptide Yes,11.1 m vs. 8.7 m, HR = 1.451, 95%CI: 1.093–1.927, p = 0.009) and (ANP) and arginine vasopressin (AVP), known to correlate with various OS(No vs. Yes,18.9 m vs. 15.8 m, HR = 1.460, 95%CI: 1.088–1.960, p = aspects of cardiopulmonary pathology, in a large cohort of SCLC patients 0.011). Multivariate analysis of clinical characteristics showed that long within a randomised controlled trial (RASTEN; Ek L. et al, Ann Oncol time second-hand smoking history(p = 0.004), cTNM stage(p < 0.001), 2018). surgery(p = 0.018), chemotherapy(p < 0.001) and PCI(p < 0.001) were Methods: Plasma concentrations of stable fragments of the peptide independent prognostic factors of OS. EGFR mutation was identified in 7 precursors midregional pro-ADM (MR-proADM), midregional pro-ANP never-smoke cases, 3 SCLC combined with adenocarcinoma. (MR-proANP) and C-terminal pre-provasopressin (copeptin, surrogate Conclusions: Although most female patients with SCLC had no history of marker of AVP) were measured in EDTA-plasma collected at baseline, smoking, the proportion of them with long-term history of second-hand using a standardised, commercial immunoluminometric sandwich assay smoke inhalation was very high. And patients with second-hand (KRYPTOR, Thermo Fisher Scientific, Germany). smoking history were tend to have worse prognosis. A relatively Results: A total of 252 RASTEN trial patients were included in the higher frequency of EGFR mutations were observed in female patients, present cohort, of which 104 (41%) had limited disease (LD) and 148 though it is still unclear how effective EGFR-TKIs are for EGFR-mutated (59%) had extensive disease (ED). For all three biomarkers, increasing SCLCs. levels were associated with reduced survival, particularly in patients Legal entity responsible for the study: Lei Yuqiong. with ED. The associations were strongest with MR-proADM, where the Funding: Has not received any funding. top versus bottom quartile was associated with an adjusted hazard ratio Disclosure: All authors have declared no conflicts of interest. (HR) for overall survival of 2.13 (95% CI 1.34–3.40; P = 0.001) in the entire cohort, and 4.08 (95% CI 2.12–7.84; P = <0.001) in patients with ED. This corresponded to a median overall survival (OS) of 6.7 months 57P and 17.1 months, in patients with the highest and lowest MR-proADM Prognostic role of lung immune scores for prediction of levels, respectively. survival in limited-stage small cell lung cancer Conclusions: In this large clinical trial cohort, we have shown that in particular MR-proADM may be a useful cardiovascular biomarker that L. Käsmann, L. Schnöller, J. Taugner, C. Eze, C. Belka, F. Manapov strongly correlates to survival in SCLC. Further prospective studies are Radiation Oncology, Ludwig Maximilians University - Grosshadern, warranted to validate the clinical utility of MR-proADM for improved, Munich, Germany individualised treatment decisions in SCLC and potentially other malignancies. Background: Definitive chemoradiotherapy is still the standard Legal entity responsible for the study: Lund University, Sweden. treatment for limited stage small cell lung cancer (LS-SCLC). Previous Funding: Governmental funding of clinical research within the national studies suggested the prognostic value of the Lung Immune Prediction health services, ALF Swedish Research Council Swedish Cancer Society. Index (LIPI) and the Gustave Roussy Score (GRIM) as prognostic markers Disclosure: All authors have declared no conflicts of interest. in advanced small cell lung cancer (SCLC). However, LIPI and GRIM score have not been evaluated in patients with LS-SCLC. Methods: Pretreatment LIPI and GRIM score of 33 (43%) patients out of 56P 77 LS-SCLC patients treated with chemoradiotherapy (CRT) during Long-time second-hand smoking as an independent 2004–2015 were included. The LIPI score was based on dNLR greater prognostic factor in female patients with small cell lung than 3 and LDH greater than upper limit of normal (ULN) and cancer: A Chinese cohort study using propensity score characterizes 3 groups (good, 0 factors; intermediate, 1 factor; poor, 2 matching factors). The GRIM score is calculated by neutrophil-to-lymphocyte ratio (>6), lactate dehydrogenase (LDH) greater than upper ULN, and serum L. Yuqiong, H. Qiang, X. Fan, T. Chu Shanghai Chest Hospital Affiliated to albumin concentration (<3,5). Both scores were calculated before start of chemoradiotherapy and follow-up was conducted until death or at Shanghai Jiao Tong University, Shanghai, China least 2 years. Background: Small cell lung cancer (SCLC) generally occurs in men, Results: The median overall survival (OS) time in the good, intermedi- mainly related to smoking. However, the main risk factors of female non- ate, and poor LIPI subgroups were 14, 17 and 3 months (p = 0.973) and smoking patients with small cell cancer are unknown. This study aims to 14, 17 and 17months in the GRIM subgroups (p = 0.984). In univariate explore the clinical characteristics of female SCLC and the influence of analysis, patients age <65years (p = 0.008), concurrent chemotherapy two major risk factors: smoking and long-term second-hand smoke (p = 0.028), and administering prophylactic cranial irradiation (PCI) inhalation on the disease. (p = 0.031) were associated with improved OS. Using Cox regression Methods: Female patients with SCLC diagnosed in Shanghai Chest analysis, age remained significant (HR = 3.299, p = 0.031) and PCI Hospital from 2014 to 2018 were enrolled. The information of smoking showed a trend (HR = 2.801, p = 0.06). history, long-term second-hand smoking history and other character- Conclusions: Independent predictors of overall survival were identified istics were evaluated. In order to reduce the bias and to scientifically and can contribute to improved treatment personalization. Concurrent evaluate the impact of smoking status and long time second-hand chemotherapy and PCI after CRT were associated with improved OS smoking status on female SCLC, we used the Propensity score matching compared to LIPI- and GRIM score, which had no prognostic impact in (PSM) analysis method to compare them in a 1:1 ratio in this non LS-SCLC. randomized study. Comprehensive genomic profiling was performed on Legal entity responsible for the study: The authors. DNA extracted from 35 samples by next generation sequencing (NGS) Funding: LMU university hospital. with a panel of 68 cancer-related genes. Disclosure: All authors have declared no conflicts of interest. Results: 323 patients were finally enrolled, including only 21(6.5%) smokers but 206(63.8%) cases with long-time second-hand smoke April 2021 Abstracts S727

Results: A total of 171 patients were included in this study. The first 58P recurrence was mainly outside the chest cavity (54.8%) and mainly Outcome and toxicity of reirradiation for locally recurrent blood tract (67.4%). Patients with liver metastasis had the worst small cell lung cancer: An international multicenter study prognosis (median DFS 9.367 months, median OS 11.900 months). The median DFS of patients with single and multiple metastatic involved L. Käsmann1, S. Janssen2, A.M. Baschnagel3, T.J. Kruser4, H. Harada5, lymph nodes were 19.233 and 9.367months(P = 0.001); the median OS M. Aktan6, D. Rades2 1Radiation Oncology, Ludwig Maximilians of patients with single and multiple metastatic involved lymph nodes University - Grosshadern, Munich, Germany; 2Radiation Oncology, were 43.033 and 17.100 months(P < 0.001). The median DFS of patients University of Luebeck, Luebeck, Germany; 3Department of Human with single- and multiple-station metastatic involved lymph nodes were Oncology, University of Wisconsin, Madison, WI, USA; 4Radiation 18.067 and 8.100 months(P < 0.001); the median OS of patients with Oncology, Northwestern University, Chicago, IL, USA; 5Division of single- and multiple-station metastatic involved lymph nodes were Radiation Therapy, Shizuoka Cancer Center, Shizuoka, Japan; 34.667 and 14.767 months(P < 0.001). 6Radiation Oncology, Necmettin Erbakan University, Konya, Turkey Conclusions: In patients with p-N2 small-cell lung cancer who had undergone radical surgery +chemotherapy +radiotherapy, the first Background: Recurrent small cell lung cancer (SCLC) is associated with progression was mainly extra-thoracic recurrence in the form of a dismal prognosis and treatment options are still limited. In this study, hematogenous metastasis. What’s more, if N2 SCLC with single lymph we evaluated the outcome of thoracic reirradiation for locally recurrent node metastasis can be identified preoperatively, surgery is also a small cell lung cancer in order to identify prognostic factors and assess treatment option. treatment-related toxicity. Legal entity responsible for the study: The authors. Methods: Data of 33 patients with a loco-regional recurrence of SCLC, Funding: The Science and Technology Innovation program of Shanghai who underwent reirradiation at 4 international university hospitals [grant number 20Y11913800]. between 2008 and 2015, were analyzed. Initial treatment consisted of Disclosure: All authors have declared no conflicts of interest. concurrent platinum-based chemoradiotherapy in 91% of all patients. Prophylactic cranial irradiation after definitive chemoradiotherapy was applied in 76% of the patients. Reirradiation doses ranged from 20 to 60TiP 87.50 Gy (median: 32.50 Gy). At the time of the second radiation course, ORIENTAL: An open label, multicenter, phase IIIb study of concurrent chemotherapy was given in 3 patients (9%) using topotecan. first-line durvalumab plus platinum-based chemotherapy Overall survival (OS), acute and late toxicities of thoracic reirradiation were evaluated and prognostic factors were identified. in Chinese patients with extensive stage small cell lung Results: Reirradiation was performed at a median interval time of 24 cancer (ES-SCLC) months after the first thoracic radiation course. Median survival after 1 2 3 4 5 6 7 reirradiation was 7 months (range, 1–54 months). The 1- and 2-year OS Y. Cheng , J. Wang , S. Cang , L. Cao , E. Chen , X. Dong ,Y.Fan , 8 9 10 11 12 13 14 were 33% and 17%, respectively. Patients with a good performance B. Gao , Q. Guo , D. Huang ,S.Li , A. Liu ,D.Lv ,Y.Pan , 15 16 17 18 19 20 1 status (KPS >70%, p = 0.016), absence of extrathoracic disease (p = K. Tang ,W.Yao ,F.Ye ,Y.Yu , A. Zang , M. Gao Jilin 2 0.001), reirradiation dose (EQD2) of >40 Gy (p = 0.019) and a Provincial Cancer Hospital, Changchun, China; National Cancer Center/ cumulative dose of first plus second series of radiotherapy (EQD2) Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union 3 >90 Gy (p = 0.019) were associated with improved OS. Acute pulmonary Medical College, Beijing, China; Henan Provincial People’s Hospital, 4 Grade 1–2 toxicity from re-irradiation was recorded in 11 patients Zhengzhou, China; The First Affiliated Hospital of USTC, University of 5 (33%) and grade 3 acute toxicity was encountered in 1 patient (3%). Science and Technology of China, Hefei, China; Sir Run Run Shaw Conclusions: Reirradiation for locally recurrent SCLC is safe and shows Hospital, Zhejiang University School of Medicine, Hangzhou, China; 6 7 promising outcomes. Patients reirradiated with doses >40 Gy experi- Wuhan Union Hospital, Wuhan, China; The Cancer Hospital of the enced more favorable survival rates. In contrast, patients with a poor University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 8 9 performance status or extrathoracic disease have a poor prognosis and Hangzhou, China; Ruijin Hospital, Shanghai, China; Shandong Cancer 10 should be considered only for symptom control in this group. Hospital and Institute, Jinan, China; Tianjin Lung Cancer Center, Tianjin, 11 Legal entity responsible for the study: The authors. China; Huashan Hospital, Fudan University, Shanghai, China; 12 Funding: LMU University Hospital. Oncology, The Second Affiliated Hospital of Nanchang University, 13 Disclosure: All authors have declared no conflicts of interest. Nanchang, China; Affiliated Taizhou Hospital of Zhejiang Province of Wenzhou Medical University, Taizhou, China; 14The First Affiliated Hospital of USTC, Anhui Provincial Hospital, Hefei, China; 15The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 16Sichuan 59P Cancer Hospital, Chengdu, China; 17First affiliated Hospital of Xiamen Patterns of recurrence and survival after complete resection University, Xiamen, China; 18Harbin Medical University Cancer Hospital, of pathological stage N2 small cell lung cancer Harbin, China; 19Affiliated Hospital of Hebei University, Baoding, China; 20Medical Affairs, AstraZeneca China, Shanghai, China L. Yu, J. Xu, R. Qiao, H. Zhong, B. Han, R. Zhong Department of Pulmonary Medicine, Shanghai Chest Hospital Affiliated to Shanghai Jiao Background: Durvalumab plus EP (etoposide with cisplatin or Tong University, Shanghai, China carboplatin) had demonstrated a significant OS benefit compared to EP alone in the 1st-line treatment naïve ES-SCLC patients in CASPIAN Background: The research on the benefits of surgical resection for study. However, there is limited safety data with the durvalumab plus EP patients with stage N2 small-cell lung cancer (SCLC) remains relatively regimen in a larger cohort of Chinese ES-SCLC patients in clinical limited. Our study was to analyse the recurrence patterns and survival of practice including in PS 2 patients and with more flexible cycles of EP. this population, especially their relationship with lymph node status, in Trial design: This study is an open-label, single-arm, multicenter, phase order to explore whether these patients could benefit from surgery in IIIb study to determine the safety of durvalumab + etoposide and addition to chemoradiotherapy. cisplatin or carboplatin as first-line treatment in Chinese patients with Methods: We retrospectively reviewed completely resected pathological ES-SCLC. About 300 eligible patients will be enrolled. Eligibility include stage N2 SCLC patients at Shanghai Chest Hospital from July 2005 to June age ≥18, histologically or cytologically documented extensive stage 2015. SCLC, ECOG performance status 0–2. Patients with PS 2 will be limited to S728 Journal of Thoracic Oncology Vol. 16 No. 4S

20% of the total study population. Patients enrolled will receive progression free at 12 months (APF12), ORR, DoR, OS, OS12, and treatment with durvalumab + etoposide with either cisplatin or incidence of AE, SAE, AESI, AE resulting in treatment discontinuation. carboplatin (EP) for 4 to 6 cycles per investigators’ clinical decision. There will be no formal interim analysis in this study. Enrollment is Durvalumab will be administered at a dose of 1500 mg every 3 weeks ongoing. (Q3W) with first-line chemotherapy (EP) and will continue to be Clinical trial identification: NCT04449861. administered as monotherapy every 4 weeks (Q4W) post-chemotherapy Legal entity responsible for the study: AstraZeneca. until progressive disease (PD) or intolerable toxicity. Prophylactic Funding: AstraZeneca cranial irradiation (PCI) is allowed at the investigators’ discretion. The Disclosure: M. Gao: Full/Part-time employment: Astrazeneca. All other authors primary endpoints are incidence of Grade ≥3 AE and incidence of imAE. have declared no conflicts of interest. Secondary endpoints include: PFS, proportion of patients alive and ABSTRACTS

Methods: The data of stage I elderly NSCLC patients (≥ 70 years) with EARLY STAGE NSCLC tumours ≤ 3 cm in diameter were extracted. Propensity-matched analysis was used. Overall survival (OS) and lung cancer-speciﬁc 61MO survival (LCSS) were compared among the patients after lobectomy Safety and efficacy of protracted stereotactic body and sub-lobar resection. The proportional hazards model was applied to identify multiple prognostic factors. radiotherapy for ultra-central lung tumours Results: 3,504 patients met criteria after propensity score matching (PSM). Although the OS was better for lobectomy than for sublobar J.E. Lodeweges1, P. Van Rossum1, M. Bartels2,V.Brand1, J. Pomp1, resection in patients with tumours ≤ 3 cm after PSM (p < 0.01), no M. Peters1, J.J.C. Verhoeff1 1Radiation Oncology, University Medical significant difference in LCSS was identified between the two treatment Center Utrecht, Utrecht, Netherlands; 2Imaging and Oncology, University groups after PSM (p = 0.144). According to subgroups of tumour sizes Medical Center Utrecht, Utrecht, Netherlands and histologic types (adenocarcinoma and other carcinomas), there were Background: For patients with early stage or medically inoperable lung no significant difference for LCSS between lobectomy and sub-lobar cancer, stereotactic body radiotherapy (SBRT) is a general accepted and resection (all P > 0.05). As for the squamous cell carcinoma, significant effective treatment option. While most successful data come from difference was observed in LCSS and OS between lobectomy and sub- peripherally located tumours, the role of SBRT in ultra-central tumours lobar resection (P < 0.05). In terms of lymph nodes, the results showed remains controversial. The aim of this single-center cohort study was to that ≥ 4 regional LNs dissection was no difference in LCSS and OS evaluate the safety and efficacy of protracted SBRT with 60 Gy in 12 between the treatment groups (p = 0.132, p = 0.713, respectively). fractions (with a biological effective dose (BED10) of 90 Gy) for patients Multivariate Cox regression showed the elder age, poor/undifferentiated with ultra-central lung tumours. grade and a large tumour size were associated with poor LCSS. The Methods: All patients with ultra-central lung tumours treated in our sublobar resection was divided into segmentectomy or wedge resection. institution with 60 Gy in 12 fractions from January 2012 until April 2020 Regardless of tumour sizes, histologic types and LNs, no significant were included. Ultra-central tumours were defined as planning target differences in LCSS were identified among the treatment subgroups (all volume (PTV) abutting or overlapping the main bronchi, trachea and/or p > 0.05). Multivariate Cox regression analysis showed the elder age, oesophagus. Data regarding patient-, tumour-, and treatment-related poor grade and large tumour size were a statistically significant characteristics were extracted from the institutional database. All patients independent factor associated with survival. were treated as per institutional protocol following International Conclusions: In terms of LCSS, lobectomy has no significant advantage Commission on Radiation Units and Measurements (ICRU) guidelines. over sub-lobar resection in elderly patients with stage IA NSCLC if lymph Results: A total of 72 patients met the criteria for ultra-central tumour node assessment is performed adequately. As for the histology of location. The PTV abutted the main bronchus, trachea or oesophagus in squamous cell carcinoma, lobectomy is still the standard surgical 78%, 21% and 21% of cases, respectively. At a median follow-up of 19 procedure. months, 1- and 2-years local failure-free survival rates were 98% and Legal entity responsible for the study: The authors. 85%, respectively. Overall survival rates at 1 and 2 years were 80% and Funding: Has not received any funding. 52% respectively. Grade 3 or higher toxicity was observed in 21%, of Disclosure: All authors have declared no conflicts of interest. which 10 patients (14% of total) died of lung haemorrhage after a median time of 11 months. A significant difference between patients ≥ with or without grade 3 toxicity was found for the mean dose (Dmean) 63MO ≥ to the main bronchus (p = 0.015), where a DmeanBED3 of 90 Gy Safety analysis of durvalumab following stereotactic body ≥ increased the risk of grade 3 toxicity significantly. radiotherapy (SBRT) in early-stage non-small cell lung cancer Conclusions: A protracted SBRT regimen of 60 Gy in 12 fractions for (NSCLC) patients: A first report of a randomized phase II trial ultra-central lung tumours leads to high local control rates with acceptable toxicity, albeit at the risk of serious toxicity and even (ASTEROID) mortality. Therefore, possible risk factors of lung hemorrhage such as 1 2 3 3 4 dose to the main bronchus, peri- or endobronchial tumour location and A. Hallqvist , H. Koyi , L. de Petris , K. Lindberg , S. Farooqi , 4 ̈ 5 6 7 8 anti–vascular endothelial growth factor (anti-VEGF) or antithrombotic Å. Helland , A. Wikstrom , M. Johansson , M. Planck , L. Lindberg , Ø. Yksnøy9, B.H. Grønberg10, N. Helbekkmo11, J. Nyman1 1Institute of therapy should be taken into account. Legal entity responsible for the study: University Medical Center Clinical Sciences, Sahlgrenska Academy, Dept. of Oncology, Sahlgrenska University Hospital, Göteborg, Sweden; 2Dept. of Oncology-Pathology, Utrecht. Karolinska Biomics Center, Karolinska institutet, Dept. of Pulmonary Funding: Has not received any funding. Medicine, Gävle, Solna, Sweden; 3Thoracic Oncology Unit Karolinska Disclosure: All authors have declared no conflicts of interest. University Hospital, Solna, Sweden; 4Dept. of Oncology, Oslo University Hospital, Oslo, Norway; 5Dept. of Pulmonary Medicine, Linköpings University Hospital, Linköping, Sweden; 6Dept. of Radiation Sciences, 62MO Umeå University, Umeå, Sweden; 7Division of Oncology, Dept. of Clinical Comparison of lobectomy and sublobar resection for stage IA Sciences, Lund University, Dept. of Pulmonary Medicine, Skåne University elderly NSCLC patients (≥70 years): A population-based Hospital, Lund, Sweden; 8Dept. of Pulmonary Medicine, Sunderbyn propensity score matching study Hospital, Luleå, Sweden, 9Dept. of Pulmonary Medicine, Ålesund Hospital, Ålesund, Norway; 10Dept. of Clinical and Molecular Medicine, NTNU, B. Zhang, W.R. Liu, D. Ren, F.X. Li, Y.Y. Wang, D.H. Huo, S. Zhu, J. Chen, Norwegian University of Science and Technology, Dept. of Oncology, St Q.Z. Song, S. Xu Department of Lung Cancer, Tianjin Medical University Olavs Hospital, Trondheim, Norway; 11Dept. of Oncology, University General Hospital, Tianjin, China. Hospital of North Norway, Tromsö, Norway Background: To investigate the differences in survival between Background: SBRT is the standard treatment for early-stage NSCLC lobectomy and sublobar resection for elderly stage I non-small cell patients that are medically unfit for surgery and is associated with lung cancer (NSCLC) patients using the Surveillance, Epidemiology, and excellent results in terms of local control. However, approximately 30% End Results (SEER) registry. of patients develop distant metastases over time. Adjuvant chemotherapy is rarely administered because of a lack of data and the fragility of

Journal of Thoracic Oncology Vol. 16 No. 4S: S729–S736 S730 Journal of Thoracic Oncology Vol. 16 No. 4S this population. Theoretically, immunotherapy is an attractive option, Conclusions: Bronchoscopic transbronchial microwave ablation is a with less toxicity and a potential synergistic effect in combination with novel, feasible and safe technique for treatment of early stage lung radiation. The ASTEROID trial aims to assess whether durvalumab cancers, lung metastases or highly suspicious lung nodules. improves outcomes after SBRT in T1-2N0M0 NSCLC patients. Herein, we Legal entity responsible for the study: The authors. present a toxicity report for the first 47 included patients. Funding: Research Grants Council (RGC) University Grant Committee Methods: Randomized multicentre open-label phase II study comparing Hong Kong, no: 14119019. SBRT alone (arm A) in 3–4 fractions with SBRT followed by adjuvant Disclosure: R.W. Lau: Advisory/Consultancy: Medtronic; Advisory/ treatment with 1500 mg durvalumab every 4 weeks (arm B). The Consultancy: Siemens Healthineer. C.S. Ng: Advisory/Consultancy: Johnson & primary endpoint is time to progression (TTP). Johnson; Advisory/Consultancy: Medtronic; Advisory/Consultancy: Siemens Healthineer. All other authors have declared no conflicts of interest. Results: Hitherto, 25 + 22 (arms A + B) patients have been included. The majority were women (66%), 66% had adenocarcinomas, 28% had PS 0, 51% PS 1 and 21% PS 2. The median age was 76 (58–89) years, 98% of the patients were former or current smokers and the mean FEV1 was 1.6 65P (0.64–4.5) L. The median number of durvalumab infusions were 11 (3– EGFR mutation (EGFRm) prevalence and mortality in patients 12) for the 24 patients who have completed treatment and 6 (1–12) for with stage IB–IIIA NSCLC: A cohort study in Denmark all patients included in this primary report. Adverse events (CTCAE v4.0) related to SBRT were reported in 7/25 patients (28%) in arm A and 6/22 E. Jakobsen1, A. Taylor2, V. Ehrenstein3 1Department of Thoracic (27%) in arm B. They were all grade 1–2 events and encompassed Surgery, Odense University Hospital, Odense, Denmark; 2Oncology pneumonitis, cough, dyspnoea, skin reactions, fatigue and pain. In arm B Business Unit, AstraZeneca, Cambridge, UK; 3Department of Clinical 12/22 patients (55%) reported AEs related to durvalumab, mainly grade Medicine, Department of Clinical Epidemiology, Aarhus University, 1 and 2, where the most common events were skin reactions/rash Aarhus, Denmark (45%), pruritus (27%) and thyroid disorders (18%). Two patients Background: Around 30% of patients with non-small cell lung cancer experienced grade 3 pneumonitis, and 1 patient grade 3 dyspnoea. Three (NSCLC) present with early-stage disease (stage I–IIIA), the primary patients had grade 3 asymptomatic hepatitis and 1 patient had grade 4 treatment for which is curative-intent complete surgical resection. asymptomatic increased lipase. Adjuvant chemotherapy is standard of care in patients with resected Conclusions: SBRT followed by adjuvant durvalumab appears to be stage II–III and selected high-risk stage IB, but recurrence rates are high. feasible and well tolerated. The trial will continue enrolment as planned This study examines the association between EGFRm and all-cause to assess the primary endpoint of TTP. mortality by stage at diagnosis and surgery in patients with stage IB–IIIA Clinical trial identification: EudraCT: 2016–005225-37 NSCLC in Denmark. NCT03446547. Methods: Historical cohort study in patients aged ≥18 years with stage Legal entity responsible for the study: Sahlgrenska University IB–IIIA NSCLC from the Danish Lung Cancer Registry (2013–2018). Hospital, Gothenburg, Sweden. Hazard ratios (aHRs) for EGFRm status and all-cause mortality rates Funding: AstraZeneca. were estimated using Cox proportional-hazards regression and stratified Disclosure: All authors have declared no conflicts of interest. by disease stage at diagnosis or surgery, adjusted for sex, age, lung function, ECOG, comorbidity, and surgery (if relevant). Results: Of 21282 NSCLC patients, 5478 (26%) had stage IB–IIIA 64MO disease, and EGFR test results were available for 2468/5478 patients Early experience of bronchoscopic transbronchial microwave (45%); of these, 195 (8%) tested positive (EGFRm). In patients with an ablation of lung nodules in the hybrid operating room available test result, 1402 (57%) were female and 1754 (71%) aged 60– 79 yrs. EGFRm prevalence was 11/5/7/7% in stage IB/IIA/IIB/IIIA, J.W.Y. Chan, R.W. Lau, C.S. Ng Cardiothoracic Surgery, The Chinese respectively. Among EGFRm patients, surgery was recorded for 124 University of Hong Kong - Prince of Wales Hospital, Sha Tin, Hong Kong, (64%), and 56/124 (45%) received adjuvant chemotherapy/radiother- China. apy. Among EGFR mutation-negative patients 1208 (53%) had record of surgery and 497/1208 (41%) received adjuvant chemotherapy/ Background: Microwave ablation of lung nodules produces faster and radiotherapy. Table shows aHRs for EGFR status associated with 1- larger ablation zones than other energy sources, while bronchoscopic year and 5-year all-cause mortality. route of access may avoid pleural-based complications associated with traditional percutaneous access. The combination of both is a novel Table 65P: EGFR status & all-cause mortality by stage/surgery approach in management of suspicious or malignant lung nodules. Methods: Lung nodule microwave ablation was performed in hybrid Mortality Stage at diagnosis Surgery operating room under electromagnetic navigation bronchoscopy guid- n/N (%) IB IIA IIB IIIA Yes No ance. Our center’s experience between March 2019 and December 2020 1 year EGFRm NR NR NR 7/62 (11) NR 10/71 (14) EGFR 81/673 37/188 98/591 230/ 117/1208 329/1065 was retrospectively analyzed. Patients had high surgical risks while lung negative (12) (20) (17) 821 (28) (10) (31) nodules were either proven malignant or radiologically suspicious. aHR (95% 0.5 NC 0.2 0.3 0.3 (0.1, 1.0) 0.3 (0.1, 0.8) Technical feasibility and safety were primarily evaluated. CI) (0.2, 1.6) (0.0, 1.4) (0.1, 0.9) Results: Total of 44 lung nodules from 36 patients were treated. Mean 5 years EGFRm 12/74 NR 10/34 26/52 25/110 26/58 (16) (29) (50) (23) (45) nodule size was 15.2 mm. Technical success rate was 100%, although EGFR 154/557 47/139 154/454 277/565 257/1020 375/695 some nodules required double ablation for adequate coverage. Mean negative (28) (34) (34) (49) (25) (54) minimal ablation margin was 5.79 mm. The mean actual ablation zone aHR (95% 0.5 0.9 (0.2, 0.8 0.8 1.0 (0.6, 1.5) 0.6 (0.3, 0.9) volume was -20.9% compared to predicted, likely due to significant CI) (0.3, 1.1) 4.0) (0.4, 1.8) (0.5, 1.3) tissue contraction ranging from 0 to 43%. There was no significant heat Values <5 masked; percent not reportable (NR); NC, not computed. sink effect. Mean hospital stay was 1.93 days, and only 2 patients stayed for more than 3 days. Complications included pneumothorax requiring drainage (6.8%), post-ablation reaction (4.5%), pleural effusion (4.5%), hemoptysis (2.3%) and bronchopleural fistula (2.3%). After median follow up of 1 year, none of the nodules had evidence of progression. April 2021 Abstracts S731

Conclusions: In this real-world Danish cohort study, EGFRm prevalence Results: Of 14452 eligible patients with stage I–III NSCLC, 3121 patients was 8% (range 5–11%) in patients with stage IB–IIIA NSCLC, and over (22%) had record of an EGFR test ≤30 days before or any time after half of EGFR-tested patients had surgery. EGFRm was associated with index; 493 (16%) were EGFRm positive (Table). Median (IQR) follow-up lower mortality, although due to small population sizes, most subgroup was 23.3 (11.2, 39.7) months (mo). In the 3121 patients with a recorded estimates should be interpreted with caution. EGFR test, median OS was 72.0 mo (95% CI 56.4, NC) in stage I, 55.5 mo Editorial acknowledgement: We acknowledge and thank Katrine (95% CI 45.9, NC) in stage II and 29.5 mo (95% CI 27.4, 33.6) in stage III. Eriksen and Bianka Darvalics for substantial input to this work. We One-yr, 2-yr and 5-yr survival rates in EGFRm-positive patients were thank Clare McCleverty PhD, contractor for Ashfield Healthcare 97%, 85% and 54% respectively, vs 83%, 64% and 38% in EGFR- Communications, Macclesfield, UK, part of UDG Healthcare plc, who negative patients, respectively. provided medical writing support funded by AstraZeneca in accordance Conclusions: In this large US analysis, 22% of patients with stage I–III with Good Publication Practice (GPP3) guidelines. NSCLC had record of an EGFR test; 16% tested were EGFRm positive. Legal entity responsible for the study: AstraZeneca. Survival rates were higher in EGFRm-positive patients vs EGFR-negative. Funding: AstraZeneca. These results reinforce the need for early diagnosis and EGFR testing to Disclosure: E. Jakobsen: Research grant/Funding (self), AstraZeneca sponsored identify patients for EGFR-TKI therapy to maximise survival outcomes. this research: AstraZeneca. A. Taylor: Shareholder/Stockholder/Stock options, Editorial acknowledgement: We thank Sally Cotterill, PhD, CMPP, from Full/Part-time employment: AstraZeneca. V. Ehrenstein: Research grant/Funding iMed Comms, an Ashfield Company, part of UDG Healthcare plc, who (institution): AstraZeneca; Full/Part-time employment: Aarhus University. provided medical writing support funded by AstraZeneca in accordance with Good Publication Practice (GPP3) guidelines. Legal entity responsible for the study: AstraZeneca. 66P Funding: AstraZeneca. EGFR testing patterns and survival in stage I–III non-small cell Disclosure: D. Potter: Research grant/Funding (self), Shareholder/Stockholder/ lung cancer (NSCLC): Analysis using the CancerLinQ Stock options: AstraZeneca. P. Sun: Shareholder/Stockholder/Stock options, Full/ ® Part-time employment: AstraZeneca. J. Li: Shareholder/Stockholder/Stock Discovery (CLQD) database options, Full/Part-time employment: AstraZeneca. L. Luo: Full/Part-time employment: AstraZeneca. A. Taylor: Shareholder/Stockholder/Stock options, Full/Part- D. Potter1,P.Sun2,J.Li3, L. Luo3, A. Taylor2 1CancerLinQ, American time employment: AstraZeneca. Society of Clinical Oncology, Alexandria, VA, USA; 2AstraZeneca, Cambridge, UK; 3AstraZeneca, Gaithersburg, MD, USA Background: The preferred treatment for early stage NSCLC (stage I– 67P IIIA) is curative-intent complete surgical resection, with adjuvant Clinical outcomes of resected EGFR positive stage I-III NSCLC chemotherapy as standard of care in resected stage II–III and selected patients in the Midlands, UK IB. Adjuvant osimertinib showed improved disease-free survival vs placebo in resected early stage EGFR mutation (EGFRm) positive NSCLC, R.L. Powell1, N. Murukesh2, P. Seeva2, A. Solanki3, A. Singh3, A. Jain4, highlighting a need for EGFR testing. Retrospective analysis of patients A.R. Elmasry5, A. Jegannathen5, A. Irwin6, Q. Ghafoor6, with stage I–III NSCLC and evidence of EGFRm testing, using the CLQD B. O’Sullivan6, P. Taniere7, S. Baijal8 1Clinical Haematology and database (de-identified electronic health record data from 47 US Oncology Department, Heartlands Hospital - University Hospitals oncology organisations). Birmingham NHS Foundation Trust, Birmingham, UK; 2Oncology Methods: Patients aged ≥18 years (yrs) with primary diagnosis of stage Department, Worcestershire Royal Hospital, Worcester, UK; 3Deanesly I–III (A and B inclusive) NSCLC 01/01/2014–31/12/2018 (index date) Centre - New Cross Hospital - The Royal Wolverhampton NHS Trust, were included. Primary objectives were to describe frequency of EGFRm Wolverhampton, UK; 4The Royal Wolverhampton Hospitals NHS Trust testing, patient characteristics, EGFRm prevalence and overall survival New Cross Hospital, Wolverhampton, UK; 5University Hospitals of North (OS). OS was defined as time from NSCLC diagnosis to death and Midlands, Stoke On Trent, UK; 6Oncology, New Queen Elizabeth Hospital summarised by Kaplan-Meier analysis. Patients without death events Birmingham, Birmingham, UK; 7Queen Elizabeth Hospital - University had OS censored at their last clinic encounter on/before 30/09/2020. Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 8Heartlands Hospital-Heart of England NHS Foundation Trust, Table 66P: Characteristics of patients with record of an EGFR test Birmingham, UK Stage I Stage II Stage III Total Background: Recently presented ADAURA study shows there is a N (%) (n = 1034) (n = 560) (n = 1527) (N = 3121) potential indication for EGFR TKIs to be offered in an adjuvant setting for Median age (IQR), years 70 (62, 76) 69 (61, 76) 67 (60, 74) 68 (60, 75) early stage resected EGFR mutant NSCLC that may improve long term Sex, female 642 (62) 304 (54) 790 (52) 1736 (56) outcomes for patients. We conducted a regional audit to collect clinical Race, white 782 (76) 401 (72) 1093 (72) 2276 (73) outcomes for EGFR positive stage I-III resected NSCLC patients. ECOG PS Methods: We used a database sourced by our pathology department 0–1 353 (34) 232 (41) 730 (48) 1315 (42) who identified all resected specimens with adenocarcinoma histology ≥ 2 80 (8) 36 (6) 138 (9) 254 (8) over a 10 year period. Those with EGFR mutation positive histology were Missing 601 (58) 292 (52) 659 (43) 1552 (50) identified and post resection treatment and clinical outcomes were EGFR mutation status* Positive 206 (20) 74 (13) 213 (14) 493 (16) obtained retrospectively from their clinical records. Negative 763 (74) 457 (82) 1246 (82) 2466 (79) Unknown 65 (6) 29 (5) 68 (4) 162 (5) *includes any EGFRm. ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; IQR, interquartile range. S732 Journal of Thoracic Oncology Vol. 16 No. 4S

Results: The primary endpoint was DFS in stage II/III (TNM 8th) patients with exploratory endpoint regarding DFS in stage I patients. Sensitivity Table 67P analyses were based on propensity score matched (PSM) cohorts. Treatment failure pattens between different TKIs were also compared. N = 31 % Results: Of 588 eligible patients, 198 patients (33.7%) received Male Female 9 22 29 71 gefitinib, 106 patients (17.9%) received erlotinib, and 284 patients Stage I Stage II Stage III 19 11 1 61.2 35.5 3.2 (48.2%) received icotinib. The median DFS of stage II/III patients in the Adenocarcinoma Adenosquamous 30 1 96.8 3.2 gefitinib, erlotinib and icotinib group were 36.1 months (95% CI, 23.9– Del exon 19 L858R G719X Other 17 10 2 2 54.8 32.3 6.5 – – 6.6 49.4), 42.8 months (95% CI, 29.6 97.8), and 32.5 months (95% CI, 23.9 Adjuvant chemotherapy 8 25.8 49.4), respectively, with no significant difference (log-rank test P = 0.22). Disease free survival (DFS) at 2 years 16 51.6 There was also no significant difference in DFS among stage I patients Progression free survival (months) 26 (95% CI 21.85– receiving different TKIs (P = 0.12). PSM adjustments and multivariate 30.15) analyses adjusting for other confounders revealed similar results. In Disease recurrence 20 64.5 addition, there was no significant differences in treatment failure pattens Treatment at recurrence TKI 16 1 1 80 5 5 in different EGFR-TKI arms, especially in terms of brain metastases Resection radiotherapy (6.1% in gefitinb, 7.5% in erlotinib, 3.9% in icotinib) and bone 2L treatment TKI IO/chemo/VEGF 4 1 20 5 metastases(8.6% in gefitinb, 9.4% in erlotinib, 7.0% in icotinib). Overall survival (months) 34 (95% CI 29.9–28.09) Conclusions: This first and largest real-world study showed that gefitinib, erlotinib, and icotinib demonstrated comparable clinical effectiveness as adjuvant therapy in completely resected patients with Conclusions: Within our cohort of patients, approximately a quarter of EGFR mutated NSCLC. our patients received adjuvant chemotherapy, relatively similar to what Legal entity responsible for the study: The authors. was observed in the ADAURA study. The majority of our patients had Funding: Has not received any funding. stage I disease which would explain the low numbers of patients Disclosure: All authors have declared no conflicts of interest. receiving adjuvant treatment. Our 2 year disease free survival was 51.6% which was highly comparable to the control arm seen in ADAURA study. Pending licensing and reimbursement of Osimertinib in the adjuvant settting for EGFR positive NSCLC patients, the treatment 69P landscape for this subgroup will change dramatically. Although our data VMAT based SBRT in early stage NSCLC: Outcomes and shows consistency with the ADAURA study control arm, the interpret- toxicities ation is limited by the small sample size and the retrospective data collection methodology. E. Martin Garcia Radiation Oncology, Hospital Universitari i Politecnic̀ La Legal entity responsible for the study: Rachel Powell. Fe, Valencia, Spain Funding: Has not received any funding. Background: For patients with early stage NSCLC unfit or unwilling to Disclosure: R.L. Powell: Advisory/Consultancy, Speaker Bureau/Expert testi- undergo surgical resection, stereotactic body radiation therapy (SBRT) is mony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker considered the election treatment. Our purpose is to analyze outcomes Bureau/Expert testimony: Bristol Myers Squibb; Speaker Bureau/Expert testi- and toxicity in primary-lung tumors treated with SBRT at our institution. mony: Boehringer Ingelheim. Q. Ghafoor: Advisory/Consultancy, Speaker Bureau/ Methods: Data from 177 patients with 203 NSCLC irradiated from May Expert testimony: AstraZeneca. S. Baijal: Advisory/Consultancy, Speaker Bureau/ 2012 to November 2018 at a single institution were retrospectively Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer. All other authors have declared no conflicts of interest. collected. Tumors were classified into central and non-central (medial or peripheral) and we reported local control (LC), overall survival (OS) and toxicity scored with CTCAE v4.03. Internal Target Volume (ITV) was defined by 4D RPM-Varian™ and expanding it uniformly 5 mm for 68P Planning Target Volume (PTV). Biologically Effective Dose (BED) Comparison of first-generation EGFR-TKIs (gefitinib, prescription was always over 100 Gy10 in 3-5-8 fractions following a erlotinib, and icotinib) as adjuvant therapy in resected risk-adapted protocol. Treatments were performed with volumetric- NSCLC patients with sensitive EGFR mutations modulated-arc-therapy planning (VMAT), 4D Cone beam CT and 4D- RPM were used to control intra-fraction movement. Follow-up was W. Liang, Q. He, C. Li, H. Liang, B. Cheng, J. He The First Affiliated performed with PET-CT or CT. Statistical analysis was conducted with R Hospital of Guangzhou Medical University, Guangzhou, China program. Results: Median age was 75 years old. The median GTV/PTV size was Background: Several randomized controlled trials have suggested that 5.6/23.7cc. Median follow-up was 17 months. Estimated global local adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase control was 96.8% (89.9–99), 87.8% (76.5–93.9) and 69.2% (40.5– inhibitors (TKIs) were associated with prolonged disease-free survival 86.1) at 24, 30 and 54 months. For central tumors: 89.1% (70–96.4) and (DFS) in EGFR-mutated NSCLC patients after radical resection, 80% (66–89) at 24 and 30 months. For non-central tumors: 96.6% comparing with chemotherapy or placebo. Herein, we aimed to (89.4–99) and 87.1% (75.2–93.5) at 24 and 30 months. Estimated global compare the effectiveness of different first-generation EGFR-TKIs as overall survival was 84.7% (78.2–89.4), 60.1% (50.9–68.2) and 50.5% adjuvant treatment in real-world setting. (40.7–59.6) at 6, 24 and 30 months. For central tumors: 85.4% (77.2– Methods: Early stage EGFR mutated NSCLC patients who underwent 89.6) and 55.8% (34.1–72.9) at 12 and 24 months. For non-central radical resection and treated with first-generation EGFR-TKIs (gefitinib, tumors: 84.5% (77.2–89.6) and 58.3% (48.7–66.8) at 12 and 24 months. erlotinib, icotinib) as adjuvant therapy between Feb 2006 and Jan 2019 From the 72 patients deceased, 27.8% were cancer-specific deaths were retrieved from a prospectively-maintained database in our center. April 2021 Abstracts S733 whilst 72.2% were attributed to other causes, mostly by cardiovascular or respiratory underlying comorbidities. Cough, dermitis or dyspnea 71P were described as mild (G1) acute toxicity in 7 patients. Chronic toxicity Assessment of chest wall toxicity after SABR for early stage was G1 pneumonitis or fibrosis in 11 patients and one patient developed lung cancers and osteoporotic risk G5 hemoptysis in a local relapse context. Conclusions: Primary lung cancer VMAT based SBRT achieves good D. Abhi1, J. Wood2, K. Mactier3, I. Phillips1, T. Evans3 1Oncology local control rates with a tolerable toxicity. Overall survival may be Department, Edinburgh Cancer Centre, Edinburgh, UK; 2Edinburgh influenced by patient selection. Cancer Centre - SCAN, Edinburgh, UK; 3Clinical Oncology, Edinburgh Legal entity responsible for the study: The author. Cancer Centre - SCAN, Edinburgh, UK Funding: Has not received any funding. Disclosure: The author has declared no conflicts of interest. Background: Aim – To identify the incidence and risk factors of chest wall toxicity in patients who have undergone stereotactic radiotherapy for early stage lung cancers at the Edinburgh Cancer Centre between 70P 2014 and 2019, particularly focusing on osteoporotic risk. 4D CT analysis of organs at risk (OARs) in stereotactic Methods: Retrospective data was collected from radiotherapy physics records to assess dose to chest wall (V30). Patient were divided into two radiotherapy cohorts. We identified 62 patients with a chest wall V30 > 30 Gy as our high-risk cohort and selected 58 patients as a random sample with a V30 V. Nardone1, F.M. Giugliano1, A. Reginelli2, S. Cappabianca3, of <30 Gy. Patient electronic notes and radiological scans were also used M. Mormile1, C. Guida1 1UOC Radioterapia, Ospedale del Mare, Naples, to collect information regarding patient demographics, pre-treatment Italy; 2Department of Precision Medicine, University of Campania, Naples, tumour characteristics and post-treatment complications. Chest wall Italy; 3Medicina di Precisione, Universitàdegli Studi della Campania Luigi toxicity was defined and graded as per CTCAE v5.0. To investigate a Vanvitelli, Caserta, Italy correlation with osteoporotic risk factors we used the FRAX clinical Background: Organs at risk (OARs) are prone to the same movements of scoring tool, scores were generated using factors at time of treatment. target volumes induced by respiratory, cardiac, and gastrointestinal Results: We identified 22 patients out of 120 with chest wall toxicity motion. OAR’s contouring usually does not consider their movements, grade 1 or above. 8 from 58 in low-risk cohort (14%, V30 < 30 Gy) and thus there are uncertainties regarding OAR dose estimation, toxicity 14 of 62 (23%, V30 > 30 Gy). Radiologically reported rib fractures were evaluation, and dose-toxicity relationship. OARs can be propagated to found in 8 of 62 patients in the high-risk cohort (12.9%, V30 > 30 Gy); obtain an internal organ at risk volume (IRV), although IRVs were never and 4 of 58 (6.89%) in the lower-risk cohort. Patient factors related to tested in a clinical setting. This work aims at studying the IRVs in a chest wall pain/rib fractures after treatment included advanced age and retrospective database of lung SABR. female sex (81.8% of those affected were female). Tumour factors Methods: Sixty patients that underwent 4DCT between August 2018 included larger sized tumours and proximity to the chest wall. We and January 2020 were included. These patients underwent radiother- calculated FRAX scores for all 120 patients and 14/22(68%) with CWT apy for either primary NSCLC or metastatic malignancies. All patients’ were below the treatment threshold. Using a chi square test (p = 0.47) clinical and pathological data, collected before RT, were recorded. For no significant correlation was found between median 10-year osteopor- each patient, OARs (heart, esophagus, trachea, spinal cord and great otic fracture and hip fracture probability in patients with chest wall vessels) were contoured using contouring atlases and international toxicity compared to the entire study cohort. guidelines and were deformably propagated across phases for obtaining Conclusions: We found that there was an increased risk of chest wall IRVs using MIM Maestro software, a commercially deformable image toxicity in patients who were older with higher rates in female patients registration tool (MIM Software Inc., Cleveland, OH, US). We correlated and an increase in median chest wall dose with higher rates in the high- the volumes of OARs with the volumes of IRVs, with the Wilcoxon sign risk cohort (V30 > 3000CGy). We assessed the risk of chest wall toxicity correlation test. A p-value ≤ 0.05 was considered as statistically and the 10-year probability of major osteoporotic fractures and hip significant. We also calculated whether IRVs still respected the fractures as calculated by the FRAX scoring tool and found no dosimetric dose constraints. The respect of dose constraints was statistically significant correlation. finally correlated with the lesions’ localization (central vs peripheral), Legal entity responsible for the study: Edinburgh Cancer Centre. with the Chi-Square test. Funding: Has not received any funding. Results: All the patients respected SABR dose constraints for standard Disclosure: All authors have declared no conflicts of interest. OARs (21). Conversely, the IRVs not respecting the dose constraints were, respectively, 7/60 (11,7%) for Heart IRV, 7/60 (11,7%) for Esophagus IRV, 11/60 (18,3%) for Trachea IRV, 16/60 (26,6%) for 72P Bronchial Tree IRV and 0/60 (0%) for great vessel IRV and spinal cord Reduction or elimination of opioids following robotic IRV. In the subset (n.38) of central targets, the percentage of the IRVs not lobectomy complying with the dose constraints are 18,4% for Heart IRV, 18,4% for Esophagus IRV, 28,9% for Trachea IRV and 42% for Bronchial Tree IRV. A. de Hoyos1, E. Stone1, E. Jaruseski2, S. Brinkman2, C. Lawson2 Conclusions: In our analysis, IRVs do not respect dose constraints in a 1Thoracic Surgery, Ascension Columbia-St Mary, Milwaukee, WI, USA; significant percentage of patients, which is even higher in central lesions 2Ascension Columbia St Mary, Milwaukee, WI, USA (up to 42%). The correlation of IRVs with clinical parameters and toxicity deserves future investigation. Background: Thoracic incisions are considered the most painful of all Legal entity responsible for the study: The authors. surgical incisions. Even with minimally invasive approaches, pain is the Funding: Has not received any funding. main driver of length of stay after uncomplicated surgery. The most Disclosure: All authors have declared no conflicts of interest. common methods for pain control include epidural catheters and opioid medications. However, many side effects are associated with them, including addiction. S734 Journal of Thoracic Oncology Vol. 16 No. 4S

Methods: Analysis of a data base analyzing the impact of a pain chemoradiotherapy groups, whereas the 5-year OS for pneumonectomy management protocol and opioid consumption after robotic lobectomy is 33–43.1% (not reported). There was no difference in efficacy between as part of ERAS pathway. Our protocol begins with admnistration of post-operative radiation therapy and chemoradiotherapy in patients acetaminophen (1 g po), celecoxib (400 mg po) and gabapentin (600 mg with NSCLC stage 1–2 in the absence of lymph node lesions or with the po) 2 hours before anesthesia. Intraoperatively, we utilize cryoanalgesia lymph node lesions. (T4-T9) and intercostal blockade with bupivacaine (01.25%). At the end Conclusions: Thus, we found a lack of high methodological quality of the operation, we give ketorolac (15–30 mg IV) and acetaminophen randomized controlled trials and works that support the great efficacy of (1 g IV). Postoperatively patients receive a combination of acetamino- any treatment method. Further large comparative studies are needed to phen, ibuprofen, gabapentin and tramadol. Other opioids are prescribed assess the intervention’s effectiveness. for brakethrough pain as prn medications. Our database and the Legal entity responsible for the study: The author. electronic health record were analyzed looking at the consumption of IV Funding: Has not received any funding. or oral opioids until the time of discharge. The Morphine Milligram Disclosure: The author has declared no conflicts of interest. Equivalent (MME) was calculated using a standard opioid conversion calculator. Pain scores and length of stay were additionally analyzed. Results: 27 patients (M = 14, F = 13) underwent robotic lobectomy for 74P – lung cancer. Mean age was 63 (55 81). Mean length of stay was 1.7 days EBUS-TBNA/EUS-B for detecting N2/N3 disease in (1–4). Pain score mean was 1.6 (0–5). Twelve patients did not receive radiologically N0/N1 non–small cell lung cancer any doses of hydromorphone (IV) or oxycodone (po). Five patients received oxycodone but not hydromorphone. Four patients received S. Rodrigues Sousa1, M.P. Valério1, J.N. Caldeira1, M. Santis2, hydromorphone but not oxycodone. The remaining six patients received P. Matos2, A.L. Fonseca2, L. Barradas2 1CHUC - Centro Hospitalar e both hydromorphone and oxycodone. Cryoanalgesia was utilized in all Universitarió de Coimbra, Coimbra, Portugal; 2Instituto Portugues patients. The calculated morphine milligram equivalents (MME) were 2 Oncologia de Coimbra Francisco Gentil E. P. E. (IPO Coimbra), Coimbra, for hydromorphone and 11.75 for oxycodone. Portugal Conclusions: A multimodality protocol for pain management in thoracic surgery patients that includes a variety of medications and techniques Background: The extent of mediastinal lymph node involvement is (including cryoanalgesia and intercostal blockade), results in a crucial in staging of potentially resectable non-small cell lung cancer significant reduction or elimination of opioid consumption, while (NSCLC). The ERS/ESTS recommends sampling of mediastinal lymph providing excellent pain relief and a short length of stay. nodes with EBUS-TBNA prior to surgery for tumours with a central Legal entity responsible for the study: The authors. location, size larger than 3 cm or N1 disease on imaging. The aim of this Funding: Has not received any funding. study was to determine the prevalence of occult N2/3 detected by EBUS- Disclosure: All authors have declared no conflicts of interest. TBNA/EUS-B for tumours radiologically staged N0/1. Methods: Data was collected from patients with radiologically staged N0/1 NSCLC by PET/CT and without metastatic disease (M0), who 73P underwent EBUS-TBNA/EUS-B for staging between 2016 and 2020, Comparison of effectiveness of different treatment tactics in based on ERS/ESTS criteria. patients with non-small cell lung cancer (stage 1A-2B) and Results: A total of 40 patients were included in the analysis. The mean age of patients was 67 years (± 9.6) and 70% were males. Of these, positive resection margin: A systematic review 82,5% (33/40) underwent EBUS-TBNA and 17,5% (7/40) underwent combined EBUS-TBNA/EUS-B. The majority of patients had radiological A. Ryzhov Medical Standardization Department, Center for Healthcare N0 disease (92,5%) and 7,5% had N1 disease. The mean size of the Quality Assessment and Control of the Ministry of Health of the Russian primary tumor on CT was 4,4 cm (± 1,6) and 37% were centrally located. Federation, Moscow, Russian Federation The prevalence of unexpected N2/N3 disease detected by EBUS-TBNA/ Background: A positive resection margin is a rather serious factor EUS-B was 15% (6/40). The totality of these occult mediastinal which negatively affects the survival of patients with locally advanced metastases was found in the subgroup of patients which were staged NSCLC. In spite of this, there is still no consensus on the tactics for previously as radiological N0. In this group, 66,7% patients (4/6) were management of such patients. In this systematic review, we have upstaged to N2 disease and 33,3% (2/6) were upstaged to N3 disease. summarized the available data of studies. There were no statistically significant differences in the prevalence of Methods: We performed a systematic literature search in PubMed, occult mediastinal metastases regarding age, gender, histology, central Elibrary, clinicaltrials.gov, and also in references of articles published location or diameter > 3 cm. The prevalence of mediastinal disease was prior to December 2020, to evaluate the possibility of these treatment also not influenced by the expression patterns of programmed death methods in indirect comparison in patients with NSCLC 1A-2B stages. In ligand 1 or the presence of any mutation in the common gene panel. In addition, we contacted some experts in this field to clarify the availability contrary, tumor location on lower right lobe showed noticeably higher of current studies on this topic. We also evaluated the methodological prevalence of occult mediastinal metastases (60%) in comparison of quality of the studies. It was not possible to perform a reliable other locations (8,8%) (p < 0,05). comparative efficacy analysis due to the study design and the data Conclusions: In this study, EBUS-TBNA/EUS-B detected occult N2/N3 presentation in the selected studies. disease in 15% of patients with radiological N0 disease. Similar rates of Results: 233 published clinical studies were found and 6 retrospective occult nodal involvement addressed by EBUS-TBNA in N0 patients were studies were selected from these. The total number of patients was 5707. found in several studies. Therefore, EBUS-TBNA can improve the Most publications had moderate methodological quality. A systematic preoperative staging of these patients compared with radiographic literature search found no studies evaluating the effectiveness of staging with PET/CT alone. combining reoperation and chemotherapy. The 3-year OS for post- Legal entity responsible for the study: The authors. operative radiation therapy is 67% (p = .86) and 59% (not reported) for Funding: Has not received any funding. reoperation. The 5-year OS is 25% to 32% (p < 0.05) for post-operative Disclosure: All authors have declared no conflicts of interest. radiation therapy groups and 33% to 44% (p ≤ 0.05) for post-operative April 2021 Abstracts S735

Legal entity responsible for the study: AstraZeneca Portugal. 75P Funding: AstraZeneca Portugal. Locally advanced, stage III non-small cell lung cancer: A highly Disclosure: F. Bernardo: Full/Part-time employment: AstraZeneca. S. Figueiredo: Full/Part-time employment: AstraZeneca. All other authors have heterogenous patient population declared no conflicts of interest.

M.A.S. Soares1, S. Gonçalves-Monteiro2, L. Antunes3, F. Bernardo4, S. Figueiredo5, M. Borges6, M.J. Bento7, P.V. Redondo2 1Medical Oncology, Instituto Portugues de Oncologia Centro do Porto (IPO-Porto), 76P Porto, Portugal; 2Outcomes Research Lab, Management, Outcomes Epithelial-to-mesenchymal transition circulating tumor cells Research and Economics in Healthcare Group, IPO Porto Research Center subtype as a biomarker in resectable NSCLC (CI-IPO), Portuguese Oncology Institute of Porto (IPO Porto), Porto, M.J. Moyano Rodriguez1, C.I. Bayarri-Lara1, D. De Miguel-Perez2, Portugal; 3Cancer Epidemiology Group, IPO Porto Research Center P. Bravo-Carmona1, A. Garcia-Diaz2, M.J. Serrano-Fernandez2 (CI-IPO), Portuguese Oncology Institute of Porto (IPO Porto), Porto, 1Thoracic Surgery, Hospital Universitario Virgen de las Nieves, Granada, Portugal; 4Evidence Generation, AstraZeneca Portugal, Barcarena, Spain; 2Biology, Centro de Genomicá e Investigacioń Oncologicá (GENYO), Portugal; 5Medical Affairs Oncology, AstraZeneca Portugal, Barcarena, Granada, Spain Portugal; 6Management, Outcomes Research and Economics in Healthcare Group, IPO Porto Research Center (CI-IPO), Portuguese Oncology Institute Background: Circulating Tumor Cells (CTCs) originate from solid of Porto (IPO Porto), Porto, Portugal; 7Department of Epidemiology, tumors and can be detected in peripheral blood by liquid biopsy due Cancer Epidemiology Group, IPO Porto Research Center (CI-IPO), to their shedding. CTCs can avoid the immune system defense, Portuguese Oncology Institute of Porto (IPO Porto). Population Studies disseminate, and participate in the metastatization process. The Department, Institute of Biomedical Sciences Abel Salazar, University of mechanism might be related to the epithelial-to-mesenchymal transition Porto, Porto, Portugal (EMT), by which CTCs are able to change their epithelial phenotype to more aggressive mesenchymal subtypes. The aim of this study is to Background: Non-small cell lung cancer (NSCLC) accounts for 85% of analyze the EMT-CTCs subtype in patients with resectable NSCLC. all lung cancers and is often diagnosed at an advanced stage. Locally Methods: We present a retrospective study based on a prospective advanced stage III NSCLC represents a highly heterogenous group of database of 97 patients with early stages (I-IIIA) of NSCLC who patients; treatment poses a challenge, as an accurate evaluation and underwent radical surgery between 2012 and 2015. Liquid biopsy staging must occur to ensure the selection of an optimal management. consisted of 15 ml of blood sample before the surgery. CTCs were Our goal was to characterize a cohort of patients diagnosed with stage III enriched by immunomagnetic techniques, EMT-CTCs were detected by NSCLC, concerning disease characteristics and treatment procedures. immunofluorescence techniques, and EGFR expression was evaluated in Methods: Real-world retrospective cohort study, including patients these EMT cells. The association between the clinical-pathological diagnosed with locally advanced stage III NSCLC between January 1st, characteristics and the presence of EMT-CTCs was analyzed, as well as 2017 and April 30th, 2018 in a Portuguese Comprehensive Cancer the value of EMT-CTCs as a prognostic factor. Center (PCCC). Data, collected from medical/administrative records, Results: Of a total of 97 patients, 50 had squamous cell carcinoma (SCC) covered demographics, tumor histology, TNM staging, ECOG perform- and 47 had adenocarcinoma (ADC) histological subtype. The TNM ance status, surgical resection, EGFR status, PD-L1 expression, treatment classification for stages was: I (45.4%), II (36.1%) y III-A (18.6%). CTCs and outcomes. Descriptive statistics analysis was conducted for were detected in 41.2% of patients. EMT-CTCs were analyzed in 54 demographic, clinical and resource utilization data. The Kaplan-Meier patients, being present in 20.4% of them. In this group, the ratio resulted method was used for survival analysis. in 1 EMT per 9.13 epithelial CTCs. All EMT-CTCs expressed EGFR. In the Results: 92 patients were included. Only 18.5% (n = 17) had resectable ADC subtype, the presence of EMT-CTCs was associated with a higher N disease. Before surgery, 29.4% (n = 5) of the patients received neo- state (p = 0.007), in contrast with the SCC subtype, which showed no adjuvant treatment. 81.5% (n = 75) had unresectable disease, and over relation with the tumor stage. During a median follow-up of 28 months, one third (37.3%) received either concurrent (17.9%; n = 5) or 43% of patients relapsed and the global mortality was 38.3%. The sequential (82.1%; n = 23) chemoradiotherapy (CRT). Tumor histology presence of EMT-CTCs in the ADC subtype was related to higher relapse of patients who received CRT was adenocarcinoma (n = 14) or risk (HR = 2.3) and worse overall survival (HR = 1.6) but with a non- squamous-cell carcinoma (n = 14). 57.1% (n = 16) of patients had statistically significant association. partial response to treatment, 21.4% (n = 6) had stable disease, and Conclusions: CTCs detection and EMT-CTCs isolation is possible by disease progression was found in 14.3% (n = 4) of patients. Those who liquid biopsy in resectable early stages of NSCLC. Further research is did not receive CRT were mostly treated only with systemic anti-cancer necessary to validate the value of EMT-CTCs as a prognosis biomarker in therapy (SACT) (66%; n = 31). The median overall survival of stage III NSCLC. – NSCLC was patients was 19.4 months (95%CI 13.9 NA). Legal entity responsible for the study: Maria Jose Moyano-Rodriguez. Conclusions: Advanced stage III NSCLC is incompatible with a unique Funding: Has not received any funding. schematic treatment approach. Multiple therapeutic strategies are Disclosure: All authors have declared no conflicts of interest. employed as a result of the high variability in tumor extent and nodal involvement. Further research on molecular and immunological characterization is required to better define targeted and effective approaches, with improved outcomes. S736 Journal of Thoracic Oncology Vol. 16 No. 4S

approach, with the aim of decreasing relapse and increasing cure rates in 77TiP early-stage NSCLC pts. From liquid biopsy to cure: Using CtDNA detection of minimal Trial design: CtDNALung is a phase II, open-label, randomized study in ≥ residual disease to identify patients for curative therapy after pts ( 18 years) with resected T1-3N0 NSCLC with elevated ctDNA levels non-small cell lung cancer (NSCLC) resection post-surgery. CtDNALung includes a screening study that enrolls pts with completely resected clinical Stage IB (≥1 cm)–IIB (per AJCC 7) NSCLC. Prospective tissue and blood is collected.Up to 180 pts will be D.C. Kelly1, L.W. le2,J.Law1, T. Stockley3, T. Waddell4, S. Bratman5, screened with ctDNA testing prior to complete surgical resection. Pts N. Leighl1 1Medical Oncology Department, University Health Network - with detectable ctDNA levels pre-operatively will be asked to repeat Princess Margaret Cancer Center, Toronto, ON, Canada; 2Department of ctDNA testing 3–6 weeks post-op. Those with detectable ctDNA levels Biostatistics, University Health Network - Princess Margaret Cancer post-operatively will be eligible to participate in a randomized Center, Toronto, ON, Canada; 3Division of Clinical Laboratory Genetics, controlled trial. From this cohort, 66 pts will be randomized (1:1) to Laboratory Medicine Program, University Health Network, Toronto, ON, receive chemo-IO or standard care observation. In the intervention Canada; 4Division of Thoracic Surgery, Toronto General Hospital, Toronto, cohort, platinum doublet will be administered for 4 cycles. It will be ON, Canada; 5Department of Radiation Oncology, University Health administered concurrently with nivolumab. The primary objective is to Network - Princess Margaret Cancer Center, Toronto, ON, Canada evaluate the impact of intensified adjuvant therapy on relapse-free Background: For resectable Stage IA2 to IIB (T1b-T3N0) NSCLC, the survival in pts with resected T1-3N0 NSCLC- with post-operative current practice is surgery followed by observation for Stage IA disease. evidence of minimal residual disease. Additional objectives include the Adjuvant platinum-based doublet chemotherapy is offered to patients safety and tolerability of adjuvant chemo-IO, overall survival, and (pts) with stage IB disease with high-risk pathological and radiological exploration of ctDNA clearance overtime. Enrolment for the ctDNA features and is recommended for those with Stage II NSCLC. In pts with screening study began in January 2021. resected lung cancer, post-operative ctDNA predicts and precedes Legal entity responsible for the study: Natasha Leighl. radiographic recurrences. The survival benefit seen with 1st-line Funding: Natasha Leighl, University Health Network, Toronto, ON, chemo-immunotherapy (chemo-IO) for advanced NSCLC provided the Canada. rationale to launch this trial offering concurrent immunotherapy with Disclosure: N. Leighl: Research grant/Funding (institution): Guardant Health; adjuvant chemo to selected pts. The current study will evaluate post- Research grant/Funding (institution): Roche; Honoraria (self), CME: BMS. All other authors have declared no conflicts of interest. operative ctDNA profiles to identify NSCLC pts at high risk for cancer recurrence that may benefit from an intensified adjuvant chemo-IO ABSTRACTS

LOCALLYADVANCED NSCLC provided by Andrew Gannon of Cirrus Communications (New York, NY), an Ashfield company, and was funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca. 78MO Funding: AstraZeneca. Disclosure: M.C. Garassino: Advisory/Consultancy, Speaker Bureau/Expert Early safety assessment of durvalumab after sCRT in patients testimony, Research grant/Funding (self), PI, MISP in Thimic malignancies; with stage III, unresectable NSCLC (PACIFIC-6) Speaker, advisory board: Eli Lilly; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ M.C. Garassino1, J. Mazieres2, M. Reck3, A. Delmonte4, H.G. Bischoff5, Funding (self), Local PI, Enrollment in clinical Trials in NSCLC; Speaker;advisory 6 7 8 7 9 board: Otsuka Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony, R. Bernabe , I. Diaz Perez ,W.Sawyer , N. Trunova , C. Faivre-Finn Research grant/Funding (self), PI, Enrollment and Steering Committee in clinical 1 2 Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Institut Trials in NSCLC; Consulting, advisory boards, lectures; steering committee: Universitaire du Cancer de Toulouse, Toulouse, France; 3Lung Clinic AstraZeneca; Advisory/Consultancy, Research grant/Funding (self), PI, Grosshansdorf, Airway Research Center North, German Center for Lung Enrollment in clinical Trials in NSCLC; advisory board: Novartis; Advisory/ 4 Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), PI, Research, Grosshansdorf, Germany; Istituto Scientifico Romagnolo per lo Enrollment in clinical Trials in NSCLC; Speaker, advisory board: BMS; Advisory/ 5 Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy; Thoraxklinik Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), PI, Heidelberg, Heidelberg, Germany; 6Hospital Universitario Virgen del Enrollment in clinical Trials in NSCLC; Speaker, advisory board: Roche; Advisory/ Rocio, Seville, Spain; 7AstraZeneca, Gaithersburg, MD, USA; 8AstraZeneca, Consultancy, Research grant/Funding (self), PI, MISP MISP Sunitinib in thymic 9 malignancies; advisory board: Pfizer; Advisory/Consultancy, Speaker Bureau/ Cambridge, UK; The University of Manchester and The Christie NHS Expert testimony, Research grant/Funding (self), PI, Enrollment in clinical Trials in Foundation Trust, Manchester, UK NSCLC; Speaker, advisory board: Celgene; Advisory/Consultancy, Speaker Bureau/ Expert testimony, Research grant/Funding (institution): Incyte; Advisory/ Background: In the ph III PACIFIC trial, durvalumab after concurrent Consultancy: Inivata; Advisory/Consultancy, Speaker Bureau/Expert testimony: chemoradiotherapy (cCRT) significantly improved survival outcomes in Takeda; Research grant/Funding (self), PI, Enrollment in clinical Trials Thimic pts with Stage III, unresectable NSCLC with manageable safety. As many malignancies: Tiziana Sciences; Research grant/Funding (self), PI, Enrollment in clinical Trials in NSCLC: Clovis; Research grant/Funding (self), PI, Enrollment in pts are ineligible for cCRT, we aimed to assess durvalumab after clinical Trials in NSCLC: Merck Serono; Advisory/Consultancy, Research grant/ sequential (s)CRT in pts with Stage III, unresectable NSCLC in the ph II Funding (self), PI, Enrollment in clinical Trials in Mesothelioma; advisory board: PACIFIC-6 trial (NCT03693300). Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ Methods: Up to 120 pts with ECOG PS ≤2 and no progression after sCRT Funding (self), PI, Enrollment in clinical Trials in NSCLC; consulting, advisory ≤ boards, lectures; steering committee: MSD; Advisory/Consultancy, Research will receive durvalumab 1500 mg IV q4w 24 months or until grant/Funding (self), Local PI, Enrollment and Steering committee in clinical progression, unacceptable toxicity or consent withdrawal. The primary Trials in NSCLC; advisory board: GlaxoSmithKline S.p.A.; Advisory/Consultancy, endpoint is assessment of safety/tolerability, defined by gr 3/4 Research grant/Funding (self), Advisory board; PI, Enrollment in clinical Trials: treatment-related AEs occurring within 6 months. Pre-specified early Sanofi-Aventis; Advisory/Consultancy, Research grant/Funding (self), PI, ≥ ∼ – Enrollment in clinical Trials; Advisory board; steering committee: Spectrum assessment was planned after 50 pts in a PS 0/1 cohort ( 100 120 Pharmaceutcials; Advisory/Consultancy, Research grant/Funding (self), PI, expected) had received durvalumab ≥6 months. Enrollment in clinical Trials; Advisory board; steering committee: Blueprint Results: As of August 24, 2020, 50 pts with ECOG PS 0/1 (46%/54%) Medicine; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Daiichi had received durvalumab for a median 24.0 weeks. Median age was 67.0 Sankyo; Research grant/Funding (institution): Merck KGaA; Advisory/ Consultancy, Research grant/Funding (self): Janssen; Non-remunerated activity/ years; 64% were male; 64% had adenocarcinoma histology; 38%/52%/ ies, Principal Investigator Keynote 189;MISP pembrolizumab in low expressors 10% had Stage IIIA/B/C disease; and 48%/52% had PD-L1 tumor cell PD-L1(J. Mazieres: Advisory/Consultancy: Merck; Advisory/Consultancy, expression ≥/< 1%. Many pts had past/present medical conditions, Research grant/Funding (self): Roche; Advisory/Consultancy, Research grant/ including vascular (62%), metabolism (54%) and respiratory (50%) Funding (self): AstraZeneca; Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Hengrui; Advisory/ disorders. Pts had received a median 4 CT cycles, with 68% receiving a Consultancy: Daiichi; Advisory/Consultancy: Boehringer; Advisory/Consultancy, total RT dose of ≥54 to ≤60 Gy and 32% receiving >60 to ≤66 Gy. In Research grant/Funding (self): Pierre Fabre. M. Reck: Honoraria (self), Honoraria most pts (84%), CT and RT did not overlap. Best response to prior sCRT for lectures and consultancy: Amgen; Honoraria (self), Honoraria for lectures and (RECIST 1.1) included PR (74%) and SD (18%). In all, 88% had any AEs consultancy: AstraZeneca; Honoraria (self), Honoraria for lectures and consultancy: BMS; Honoraria (self), Honoraria for lectures and consultancy: Boehringer and 12% had gr 3/4 AEs; 70% had any possibly related AEs (PRAEs) and Ingelheim; Honoraria (self), Honoraria for lectures and consultancy: Lilly; 4% had gr 3/4 PRAEs (including 2% with the gr 3/4 PRAE Honoraria (self), Honoraria for lectures and consultancy: Merck; Honoraria pneumonitis). 22% had SAEs (10% PRSAEs) and 2 pts had fatal AEs (self), Honoraria for lectures and consultancy: MSD; Honoraria (self), Honoraria (1 pt fatal PRAE). 72% had AESIs, including pneumonitis (32%) and for lectures and consultancy: Novartis; Honoraria (self), Honoraria for lectures and consultancy: Pfizer; Honoraria (self), Honoraria for lectures and consultancy: dermatitis/rash (28%). 9/25 pts who discontinued did so due to AEs, Roche; Honoraria (self), Honoraria for lectures and consultancy: Samsung. most commonly pneumonitis (n = 8). R. Bernabe: Research grant/Funding (institution): Roche. I. Diaz Perez: Conclusions: Based on early assessment, durvalumab after sCRT Shareholder/Stockholder/Stock options, Full/Part-time employment: appears to have a similar safety profile to that with durvalumab after AstraZeneca. W. Sawyer: Full/Part-time employment, Contractor: AstraZeneca. N. Trunova: Shareholder/Stockholder/Stock options, Full/Part-time employment: cCRT in PACIFIC pts with Stage III, unresectable NSCLC. Full cohort AstraZeneca. C. Faivre-Finn: Advisory/Consultancy, Research grant/Funding results for safety primary analysis in the near future are awaited. (self), Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding Clinical trial identification: NCT03693300. (self), Travel/Accommodation/Expenses: Elekta. All other authors have declared Editorial acknowledgement: Medical writing support, which was in no conflicts of interest. accordance with Good Publication Practice (GPP3) guidelines, was

Journal of Thoracic Oncology Vol. 16 No. 4S: S737–S747 S738 Journal of Thoracic Oncology Vol. 16 No. 4S

(except France: durvalumab start ≤6 weeks from end of CRT per 79MO protocol). Permanent discontinuation due to AESIs was infrequent. PACIFIC-R: Real-world characteristics of unresectable stage III Clinical trial identification: NCT03798535. NSCLC patients treated with durvalumab after Editorial acknowledgement: Medical writing support, which was in chemoradiotherapy accordance with Good Publication Practice (GPP3) guidelines, was provided by Carole Mongin-Bulewski of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca. F. McDonald1, F. Mornex2, M.C. Garassino3, A.R. Filippi4, Legal entity responsible for the study: AstraZeneca plc. D. Christoph5, V.D. Haakensen6, A. Agbarya7, M. Van den Heuvel8, Funding: AstraZeneca. P. Vercauter9, C. Chouaid10, E. Pichon11, S. Siva12, L. Steinbusch8, 13 14 15 16 17 Disclosure: F. McDonald: Honoraria (self), Advisory/Consultancy: AstraZeneca; I. Peretz , B. Solomon , L. Decoster ,W.Sawyer , A. Allen , Honoraria (self): Elekta; Advisory/Consultancy: Accuracy; Research grant/ 18 19 1 M. Licour , N. Girard Lung Unit, Royal Marsden Hospital NHS Funding (institution): MSD. M.C. Garassino: Advisory/Consultancy, Speaker Foundation Trust, London, UK; 2Department of Radiation Oncology, Centre Bureau/Expert testimony, Research grant/Funding (self), PI, MISP in Thimic Hospitalier Universitaire de Lyon, Lyon, France; 3Medical Oncology malignancies; Speaker, advisory board: Eli Lilly; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony, Division, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, 4 Research grant/Funding (self), Local PI, Enrollment in clinical Trials in NSCLC; Milan, Italy; Radiation Oncology Department, Fondazione IRCCS Speaker; advisory board: Otsuka Pharma; Advisory/Consultancy, Research grant/ Policlinico San Matteo and University of Pavia, Pavia, Italy; 5Medical Funding (self), PI, Enrollment and Steering Committee in clinical Trials in NSCLC; Oncology Department, Evangelische Kliniken Essen-Mitte, Evangelische consulting, advisory boards, lectures;steering committee: AstraZeneca; Advisory/ 6 Consultancy, Research grant/Funding (self), PI, Enrollment in clinical Trials in Huyssens-Stiftung, Essen, Germany; Department of Oncology, Oslo NSCLC; advisory board: Novartis; Advisory/Consultancy, Speaker Bureau/Expert 7 University Hospital, Oslo, Norway; Oncology Department, Bney Zion testimony, Research grant/Funding (self), PI, Enrollment in clinical Trials in Medical Center, Haifa, Israel; 8Department of Thoracic Oncology, The NSCLC; Speaker, advisory board: BMS; Advisory/Consultancy, Speaker Bureau/ Netherlands Cancer Institute, Amsterdam, Netherlands; 9Department of Expert testimony, Research grant/Funding (self), PI, Enrollment in clinical Trials in NSCLC; Speaker, advisory board: Roche; Advisory/Consultancy, Research grant/ Pneumology, Onze-Lieve-Vrouw Ziekenhuis Aalst, Aalst, Belgium; 10 11 Funding (self), PI, MISP MISP Sunitinib in thymic malignancies; advisory board: Services de Pneumologie, CHI Creteil,́ Creteil,́ France; Services de Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ Pneumologie, CHRU de Tours, Hôpital Bretonneau, Tours, France; Funding (self), PI, Enrollment in clinical Trials in NSCLC; Speaker, advisory board: 12Department of Oncology, Sir Peter MacCallum Cancer Centre, Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research 13 grant/Funding (institution), Institutional Grants; Advisory board; Speaker: Melbourne, Australia; Institute of Oncology, Clalit Health Services, Tel Incyte; Advisory/Consultancy: Inivata; Advisory/Consultancy, Speaker Bureau/ 14 Aviv, Israel; Department of Medical Oncology, Sir Peter MacCallum Expert testimony: Takeda; Research grant/Funding (self), PI, Enrollment in Cancer Centre, University of Melbourne, Melbourne, Australia; clinical Trials Thimic malignancies: Tiziana Sciences; Research grant/Funding 15Department of Medical Oncology, Universitair Ziekenhuis Brussel, Vrije (self), PI, Enrollment in clinical Trials in NSCLC: Clovis; Research grant/Funding (self), PI, Enrollment in clinical Trials in NSCLC: Merck Serono; Advisory/ Universiteit Brussel, Brussels, Belgium; 16AstraZeneca, Cambridge, UK; 17 18 Consultancy, Research grant/Funding (self), PI, Enrollment in clinical Trials in AstraZeneca, Gaithersburg, MD, USA; Astrazeneca, Paris, France; Mesothelioma; advisory board: Bayer; Advisory/Consultancy, Speaker Bureau/ 19Institut du Thorax, Institut Curie et Montsouris, Paris, France Expert testimony, Research grant/Funding (self), PI, Enrollment in clinical Trials in NSCLC; consulting, advisory boards, lectures; steering committee: MSD; Advisory/ Consultancy, Research grant/Funding (self), Local PI, Enrollment and Steering Background: The PACIFIC regimen (up to 12 months of durvalumab committee in clinical Trials in NSCLC; advisory board: GlaxoSmithKline S.p.A.; treatment in pts with unresectable stage III non-small cell lung cancer Advisory/Consultancy, Research grant/Funding (self), Advisory board; PI, [NSCLC] who did not progress after platinum-based concurrent Enrollment in clinical Trials: Sanofi-Aventis; Advisory/Consultancy, Research grant/Funding (self), PI, Enrollment in clinical Trials; Advisory board; steering chemoradiotherapy [cCRT]) is now standard of care. Insights into committee: Spectrum Pharmaceutcials; Advisory/Consultancy, Research grant/ durvalumab use outside the clinical trial setting are needed. Funding (self), PI, Enrollment in clinical Trials; Advisory board; steering Methods: PACIFIC-R (NCT03798535) is a large international, observa- committee: Blueprint Medicine; Advisory/Consultancy: Seattle Genetics; tional study of pts with unresectable Stage III NSCLC who received ≥1 Advisory/Consultancy: Daiichi Sankyo; Research grant/Funding (institution): Merck KGaA; Advisory/Consultancy, Research grant/Funding (self): Janssen; Non- dose of durvalumab (10 mg/kg Q2W) as part of an AstraZeneca-initiated remunerated activity/ies, Principal Investigator Keynote 189;MISP pembrolizu- expanded access programme (September 2017–December 2018). Pts mab in low expressors PD-L1(A.R. Filippi: Advisory/Consultancy, Scientific must have completed platinum-based chemotherapy (CT) concurrent or consultancy; advisory board: AstraZeneca; Speaker Bureau/Expert testimony: sequential to radiotherapy (RT) within the previous 12 weeks without Roche; Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: MSD. D. Christoph: Honoraria (self), Non-remunerated activity/ies, evidence of disease progression. Data will be retrospectively collected up Personal fees and non-financial support: AstraZeneca; Honoraria (self), Non- to 5 years after enrolment. remunerated activity/ies, Personal fees and non-financial support: Boehringer Results: The full analysis set (N = 1155) showed no significant Ingelheim; Honoraria (self), Non-remunerated activity/ies, Personal fees and non- differences in baseline demographics and disease characteristics by financial support: Bristol-Myers Squibb; Honoraria (self), Non-remunerated ≥ activity/ies, Personal fees and non-financial support: Chugai; Honoraria (self), PD-L1 expression status (tested pts: 1% [n = 574] vs <1% [n = 138]). A Non-remunerated activity/ies, Personal fees and non-financial support: Merck, majority of pts had received cCRT (n = 893). Pts who had received Sharp & Dohme; Honoraria (self), Non-remunerated activity/ies, Personal fees and sequential CRT (sCRT; n = 163) were generally older (37.4% vs 28.4% non-financial support: Novartis; Honoraria (self), Non-remunerated activity/ies, aged ≥70 years); a higher proportion had larger tumour volume (25.0% Personal fees and non-financial support: Pfizer; Honoraria (self), Non-remunerated activity/ies, Personal fees and non-financial support: Roche; Honoraria (self), vs 15.9% >70 mm). Median total RT dose (overall: 65 Gy) and duration Non-remunerated activity/ies, Personal fees and non-financial support: Takeda; (overall: 1.5 months) reflected local practice. For platinum-based CT Honoraria (self), Non-remunerated activity/ies, Personal fees and non-financial regimens, vinorelbine was favoured in France/Germany/UK; paclitaxel support: Bayer. A. Agbarya: Non-remunerated activity/ies, Non-financial support: in Australia/Israel; and etoposide in Netherlands/Belgium/Norway. AstraZeneca. M. Van den Heuvel: Research grant/Funding (self), Research projects, not related to Pacific R: AstraZeneca. C. Chouaid: Advisory/Consultancy, Speaker Median CT duration ranged from 0.8 to 2.3 months (overall: 1.6 months). Bureau/Expert testimony, Research grant/Funding (self), Received fees for Median time of durvalumab start from end of CRT varied from 39 to 89 attending scientific meetings; speaking; organizing research; consulting within days (overall: 52 days). Most commonly reported adverse events of past five years: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert special interest (AESIs) in the first 3 months of durvalumab treatment testimony, Research grant/Funding (self), Received fees for attending scientific meetings; speaking; organizing research; consulting within past five years: were pneumonitis (10.6%) and endocrinopathies (6.8%), leading to Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony, permanent treatment discontinuation in 4.8% and 0.2% of pts, Research grant/Funding (self), Received fees for attending scientific meetings; respectively. speaking; organizing research; consulting within past five years: GSK; Advisory/ Conclusions: Real-world characteristics of PACIFIC-R pts reflect the Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Received fees for attending scientific meetings; speaking; organizing research; PACIFIC population (only cCRT was allowed per protocol in PACIFIC). consulting within past five years: Roche; Advisory/Consultancy, Speaker Bureau/ Time to durvalumab start from end of CRT was longer than in PACIFIC Expert testimony, Research grant/Funding (self), Received fees for attending April 2021 Abstracts S739 scientific meetings; speaking; organizing research; consulting within past five Methods: In two lung cancer centers, 35 patients with NSCLC and a years: Sanofi Aventis; Advisory/Consultancy, Speaker Bureau/Expert testimony, potentially curative stage (including 12 patients with oligometastatic Research grant/Funding (self), Received fees for attending scientific meetings; speaking; organizing research; consulting within past five years: BMS; Advisory/ disease) were prospectively included if curative treatment (either Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), definitive RCT or resection) could not be performed due to large tumor Received fees for attending scientific meetings; speaking; organizing research; size or for functional reasons (e. g. too large radiation field or consulting within past five years: MSD; Advisory/Consultancy, Speaker Bureau/ functionally inoperable for the required resection). For these patients, Expert testimony, Research grant/Funding (self), Received fees for attending scientific meetings; speaking; organizing research; consulting within past five the multidisciplinary tumor board (MDB) recommended palliative C-IO years: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research and re-evaluation including PET-CT if indicated. After review of the grant/Funding (self), Received fees for attending scientific meetings; speaking; MDB, patients received either definitive curative treatment or palliative organizing research; consulting within past five years: Novartis; Advisory/ treatment. Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), – Received fees for attending scientific meetings; speaking; organizing research; Results: 14, 14, and 7 patients had a PD-L1 score (TPS) of 50%, 1 49%, consulting within past five years: Pfizer; Advisory/Consultancy, Speaker Bureau/ and 0%, respectively. Patients completed 1–4 cycles of neoadjuvant Expert testimony, Research grant/Funding (self), Received fees for attending therapy, 5 as mono immunotherapy, and 30 as chemo-immunotherapy. scientific meetings; speaking; organizing research; consulting within past five The primary endpoint of definitive therapy was reached by 29 patients years: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Received fees for attending scientific meetings; (83%). Of these, 11 were R0-resected, 18 received curative-dose radio- speaking; organizing research; consulting within past five years: Takeda; chemotherapy. Six patients remained palliative (2 incomplete resections Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ (R1-R2), 4 palliative systemic therapy). The study is positive for the Funding (self), Received fees for attending scientific meetings; speaking; primary endpoint (predefined >80%). According to RECIST, 76% had organizing research; consulting within past five years: Bayer; Advisory/ Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), complete or partial response. Of 27 patients evaluable for metabolic Received fees for attending scientific meetings; speaking; organizing research; response (PERCIST), 7 (26%) had complete metabolic response. Of the consulting within past five years: Amgen. E. Pichon: Honoraria (self), Non- surgical patients, 6 of 11 completely resected patients (56%) had a remunerated activity/ies, Personal fees and non-financial support: Bristol Myers complete or major pathological response. After a median follow-up of 15 Squibb; Honoraria (self), Non-remunerated activity/ies, Personal fees and non- financial support: Takeda; Non-remunerated activity/ies, Non-financial support: months, there were 13 recurrences (9 of 29 curative patients [31%], 4 of Merck Serono; Non-remunerated activity/ies, Non-financial support: AstraZeneca; 6 palliative patients [67%]), and 5 patients had died (3 of 29 curative Honoraria (self), Personal fees: Roche. S. Siva: Speaker Bureau/Expert testimony, patients [10%], 2 of 6 palliative patients [33%]). Treatment was well Travel/Accommodation/Expenses, Speaker fees to institution and travel: tolerated with no new safety signals. AstraZeneca; Research grant/Funding (self), Research grant, un-related: Varian Industries. B. Solomon: Honoraria (self), Advisory/Consultancy: AstraZeneca; Conclusions: In routine clinical practice, neo-adjuvant C-IO is feasible Honoraria (self), Advisory/Consultancy: Roche/Genentech; Honoraria (self), for patients with locally advanced or oligometastatic NSCLC and results Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Novartis; in a high rate of curative treatment. Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/ Legal entity responsible for the study: The authors. Consultancy: Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy: Merck. L. Decoster: Research grant/Funding (self), Data monitoring: Funding: Has not received any funding. AstraZeneca; Travel/Accommodation/Expenses, Travel grant: Roche Belgium; Disclosure: M. Faehling: Advisory/Consultancy, Research grant/Funding Research grant/Funding (self): Boehringer Ingelheim; Travel/Accommodation/ (institution): Roche; Advisory/Consultancy: BMS; Advisory/Consultancy, Expenses, Travel grant: MSD Belgium. W. Sawyer: Full/Part-time employment: Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, AstraZeneca. M. Licour: Shareholder/Stockholder/Stock options, Full/Part-time Research grant/Funding (institution): MSD. All other authors have declared no employment, Employment/stock options: AstraZeneca. N. Girard: Honoraria (self), conflicts of interest. Non-remunerated activity/ies, Personal fees and non-financial support outside the submitted work: AstraZeneca; Honoraria (self), Non-remunerated activity/ies, Personal fees and non-financial support outside the submitted work: BMS; Honoraria (self), Non-remunerated activity/ies, Personal fees and non-financial support outside the submitted work: MSD. All other authors have declared no conflicts of interest.

80P Prospective analysis of patients with non-small cell lung cancer (NSCLC) receiving neoadjuvant (chemo-) immunotherapy (C-IO) prior to resection or definitive radiochemotherapy (RCT) in routine clinical care (KOMPASS neo)

M. Faehling1,A.Türk2, R. Saetzler2, S. Fallscheer1, J. Sträter3, S. Eschmann4, F. Heinzelmann5, H. Witte6 1Cardiology/Pneumology, Klinikum Esslingen, Esslingen am Neckar, Germany; 2Thoracic Surgery, Klinikum Esslingen, Esslingen am Neckar, Germany; 3Institut für Pathologie, Esslingen, Germany; 4Nuklearmedizin, Marienhospital Stuttgart, Stuttgart, Germany; 5Strahlentherapie, Klinikum Esslingen, Esslingen am Neckar, Germany; 6Haematology and Oncology, Bundeswehrkrankenhaus, Ulm, Germany Background: Recent phase I and phase II trials report the feasibilitiy of neoadjuvant C-IO prior to surgery or definitive RCT. Furthermore, the studies report high rates of pathological remission, a surrogate marker for overall survival. S740 Journal of Thoracic Oncology Vol. 16 No. 4S

immune status from blood is a valid source of pneumonitis predictive 81P biomarkers and supports further studies in larger cohorts. Predictive molecular parameters of pneumonitis Legal entity responsible for the study: Spanish Lung Cancer Group. development in stage IIIa NSCLC patients treated with Funding: Bristol-Myers Squibb, Instituto de Salud Carlos III, European ’ neo-adjuvant chemo-immunotherapy from NADIM Union s Horizon 2020 research and innovation programme. Disclosure: E. Nadal: Advisory/Consultancy: Bristol-Myers-Squibb; Advisory/ clinical trial Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Lilly; Advisory/ B. Sierra-Rodero1, Y. Garitaonaindia2, M. Martinez-Cutillas2, Consultancy: Amgen; Advisory/Consultancy: Boehringer Ingelheim. A. Insa: E. Nadal3, A. Insa4, M.R. Garcia Campelo5, J. Casal Rubio6, Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/ 7 8 9 Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony: M. Domine Gomez , M. Majem Tarruella , D. Rodriguez Abreu , AstraZeneca. M.R. Garcia Campelo: Advisory/Consultancy: AstraZeneca; A. Martinez-Marti10, J. De Castro Carpeno11, E. del Barco12, Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: MSD; N. Viñolas13, I.C. Barneto Aranda14, B. Massuti Sureda15, Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche. M. Domine Gomez: M. Casarrubios1, R. Laza-Briviesca1, A. Cruz-Bermudez1, Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bristol-Myers 2 1 Squibb; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: M. Provencio Medical Oncology, Fundacion Para La Investigacion MSD; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche. M. Majem Biomedica Del Hospital Universitario Puerta De Hierro Majadahonda, Tarruella: Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/ Majadahonda, Spain; 2Medical Oncology, Hospital Universitario Puerta de Consultancy: MSD; Advisory/Consultancy: Boehringer Ingelheim; Advisory/ Hierro-Majadahonda, Majadahonda, Spain; 3Medical Oncology Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Advisory/Consultancy: ̀’ ’ Kyowa Kirin; Advisory/Consultancy: Pierre Fabre. D. Rodriguez Abreu: Advisory/ Department, ICO - Institut Catala d Oncologia l Hospitalet (Hospital Consultancy: Bristol-Myers-Squibb; Advisory/Consultancy: Genentech/Roche; 4 Duran i Reynals), L′Hospitalet De Llobregat, Barcelona, Spain; Medical Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Advisory/ Oncology Department, Hospital Clınicó Universitario de Valencia, Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Novartis; Advisory/ Valencia, Spain; 5Dept. Medical Oncology, Instituto de Investigacioń Consultancy: Lilly. A. Martinez-Marti: Advisory/Consultancy: AstraZeneca; ́ ̃ ̃ 6 Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Merck Biomedica de A Coruna (INIBIC), A Coruna, Spain; Hospital Universitario Sharp and Dohme; Advisory/Consultancy: Pfizer; Advisory/Consultancy: 7 Alvaro Cunqueiro, Vigo, Ponteverdra, Spain; University Hospital Boehringer Ingelheim; Advisory/Consultancy: MSD Oncology. J. De Castro "Fundacion Jimenez Diaz", Madrid, Spain; 8Hospital de la Santa Creu i Carpeno: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Sant Pau, Barcelona, Spain; 9Medical Oncology Department, Hospital Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Travel/ Accommodation/Expenses: Merck Sharp and Dohme; Advisory/Consultancy, Universitario Insular de Gran Canaria - Complejo Hospitalario Materno- Travel/Accommodation/Expenses: Hoffmann-la Roche; Advisory/Consultancy: 10 Insular, Las Palmas De Gran Canaria, Canary Islands, Spain; Medical Bristol Myers Squibb; Advisory/Consultancy: Takeda; Advisory/Consultancy: Oncology Dept., Vall d’Hebron Institute of Oncology and University Pfizer; Advisory/Consultancy: Novartis. I.C. Barneto Aranda: Advisory/ Hospital, Barcelona, Spain; 11Departimento Oncologia Medica, Hospital Consultancy: Bristol-Myers-Squibb; Advisory/Consultancy: Takeda; Advisory/ 12 Consultancy: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Universitario La Paz, Madrid, Spain; Oncology, University Hospital of Boehringer Ingelheim. B. Massuti Sureda: Advisory/Consultancy, Research grant/ 13 Salamanca, Salamanca, Spain; Division of Medical Oncology, Hospital Funding (self), Personal fees: Roche; Advisory/Consultancy: BMS; Advisory/ Clinic of Barcelona, Barcelona, Spain; 14University Hospital Reina Sofia, Consultancy: Takeda; Advisory/Consultancy: Boehringer Ingelheim. M. Provencio: Cordoba, Spain; 15Medical Oncology Department, Hospital General Advisory/Consultancy, Research grant/Funding (self), Non-remunerated activity/ ies: BMS; Advisory/Consultancy, Research grant/Funding (self), Non-remunerated Universitario de Alicante, Alicante, Spain activity/ies: Roche; Advisory/Consultancy, Research grant/Funding (self), Non- remunerated activity/ies: AstraZeneca; Advisory/Consultancy: MSD; Advisory/ Background: Pneumonitis is a common adverse event in patients Consultancy: Takeda. All other authors have declared no conflicts of interest. treated with immunotherapy, involving treatment interruptions and potentially life-threatening situations. The aim of this study is to define a set of molecular parameters in pre-treatment blood samples of NSCLC 82P patients treated with neo-adjuvant chemoimmunotherapy that will help to predict patients likely to develop immune-mediated pneumonitis. Multicenter analysis of neoadjuvant (chemo-)immunotherapy Methods: Treatment related adverse events and clinical variables of 46 (C-IO) in stage IIB-IVB non-small cell lung cancer (NSCLC) potentially resectable stage IIIa NSCLC patients included in the NADIM resulting in curative surgery in routine clinical care clinical trial (NCT03081689) were analyzed. A semi-quantitative study (KOMPASS neo OP) of 200 plasma cytokine baseline levels was conducted in 30 patients, and peripheral blood mononuclear cells immunophenotype from 29 patients M. Faehling1, C. Meyer zum Büschenfelde2, M. Sebastian3, H. Witte4, at diagnosis was characterized by flow cytometry. A comparative M. Ulmer5,A.Türk6, R. Saetzler6, K. Steinestel7, W.M. Brueckl8, analysis was made with non-parametric methods between the A. Bleckmann9 1Cardiology/Pneumology, Klinikum Esslingen, Esslingen development of immune-mediated pneumonitis of any grade during am Neckar, Germany; 2St.Vincentius-Kliniken Karlsruhe, Karlsruhe, neoadjuvant treatment, and clinical and molecular variables. Germany; 3Department of Hematology/Medical Oncology, Results: Among pneumonitis patients 78.6% were men, with a median Universitätsklinikum Frankfurt (Johannes-Wolfgang Goethe Institute), age of 62.5 years and 42.9% smokers. No significant differences were Frankfurt am Main, Germany; 4Haematology and Oncology, found between patients developing pneumonitis in terms of age, sex Bundeswehrkrankenhaus, Ulm, Germany; 5Medizinische Klinik I, Klinikum and smoking habits. Patients who developed pneumonitis had Ludwigsburg, Ludwigsburg, Germany; 6Thoracic Surgery, Klinikum significant reduced cytokine levels of Cripto1, GCP2, and elevated Esslingen, Esslingen am Neckar, Germany; 7University Hospital of MSPa (p-values 0.010, 0.041 and 0.026). Referring to immune cells, Münster, Münster, Germany; 8Nuremberg Lung Cancer Center, Paracelsus pneumonitis patients had a significant higher percentage of CD56+PD1- Medical University, Klinikum Nuernberg Nord, Nürnberg, Germany; and CD8+PD1- populations, and reduced CD4+PD1+ (p-values 0.009, 9CCCM and Department of Hematology, Oncology and, UKM - University 0.019 and 0.032). The area under the ROC curves for pneumonitis Hospital of Münster, Münster, Germany development were 0.826, 0.758 and 0.783 for Cripto1, GCP2 and MSPa Background: Recent phase I and phase II trials report the feasibility of levels; and 0.831, 0.799 and 0.773 for CD56+PD1-, CD8+PD1- and CD4 neoadjuvant C-IO prior to surgery. Furthermore, the studies report high +PD1+ populations.. pathological response rates which might be a surrogate marker for Conclusions: In this study we describe a novel set of molecular overall survival (OS). parameters, such as cytokine levels and PBMCs populations at diagnosis, Methods: This is a retrospective multicenter real-world analysis of which are able to predict pneumonitis development in a context of patients with locally resectable NSCLC including oligometastatic disease, chemoimmunotherapy. These results indicate that the study of the basal who received neoadjuvant C-IO and subsequent resection. Following April 2021 Abstracts S741 resection, consolidating immunotherapy could be administered accord- evaluated retrospectively and the outcome in the group of PD-L1 <1% ing to multi-disciplinary board (MDB) recommendation. Primary and PD-L1 >1% was compared. endpoint was the rate of complete pathological response (CPR) or Methods: Clinical data and tumor characteristics were systematically major pathological response (MPR). Secondary endpoints included the captured from the data base of the certified lung cancer center, including proportion of partial remission (PR) or complete remission (CR) PD-L1-score. In case, PD-L1 expression had not been evaluated, the according to RECIST, the feasibility of R0 resection, recurrence-free available tissues samples were tested retrospectivley. The clinical survival, and overall survival. parameters comprise age, gender, histology, smoking history, ECOG- Results: Seven experienced thoracic oncology centers contributed status, type of first line treatment, Albumin, CRP, PFS and OS. 50 patients. At baseline, 30 and 20 patients were diagnosed UICC Results: The study showed that the expression of PD-L1 is independent stage IIB – IIIC and IVA – IVB with up to 3 oligometastatic sites, from gender and histology. The median OS of the patients with an respectively. 47 patients received neoadjuvant chemo-immunotherapy, expression of PD-L1 <1% was 27 months and with an expression ≥1% 3 patients received neoadjuvant mono immunotherapy. Postoperatively, 19 months, however this difference was not statistically significant. The 12 patients received consolidating immunotherapy. With respect median PFS of the patients with an expression of PD-L1 <1% was 9 to the secondary endpoints, 2, 39, and 9 patients (4%, 78%, and 18%) months and with an expression ≥1% 10 months, also not being had radiological CR, PR, and stable disease, respectively. 47 patients statistically significant. However, CRP values had a significant impact on (94%) were curatively resected (R0). 31 patients (62%) achieved OS with 27 months for low CRP vs.17 months for high CRP, this CPR (26) or MPR (5). After a median follow-up of 16 months, difference was statistically significant with a p-value of 0.035. The other there were 6 recurrences (12%). Of these, 3 occurred in patients with clinical parameters did not impact the OS. CPR, and 4 occurred in stage IV patients. 3 patients had died (1 due to Conclusions: This study showed that the assumption of lack of PD-L1 progression, 1 due to pneumonia post-operatively, 1 due to pneumonia expression after radio-chemotherapy conferring good outcome vs. PD- during follow-up). Treatment was well tolerated with no new safety L1 expression >1% couldn’t be approved in our patient cohort. signals. Legal entity responsible for the study: University Hospital for Internal Conclusions: In routine clinical practice, resection after neo-adjuvant C- Medicine-Oncology, Pius Hospital Oldenburg, University of Oldenburg. IO is feasible and safe with high rates of CPR or MPR, even in Funding: Has not received any funding. oligometastatic patients. Recurrences occurred despite CPR and were Disclosure: J. Roeper: Honoraria (self): Boehringer Ingelheim; Honoraria (self): found mainly in stage IV patients. Early follow-up data are encouraging AstraZeneca; Honoraria (self): Roche. L.C. Heukamp: Honoraria (self), Advisory/ and comparable to those in clinical trials. Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Legal entity responsible for the study: The authors. Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Novartis; Funding: Has not received any funding. Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/ Disclosure: M. Faehling: Advisory/Consultancy, Research grant/Funding Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Siemens. (institution): MSD; Honoraria (self), Advisory/Consultancy, Research grant/ F. Griesinger: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert Funding (institution): Roche; Honoraria (self), Advisory/Consultancy, Research testimony, Research grant/Funding (institution), Travel/Accommodation/ grant/Funding (institution): AstraZeneca; Advisory/Consultancy: BMS; Advisory/ Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Consultancy: Sanofi. C. Meyer zum Büschenfelde: Advisory/Consultancy: Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/ MSD; Advisory/Consultancy: Roche; Advisory/Consultancy: BMS. M. Sebastian: Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/ Advisory/Consultancy: Sanofi; Advisory/Consultancy: MSD; Advisory/ Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Consultancy: Roche; Advisory/Consultancy: BMS. M. Ulmer: Advisory/ Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/ Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Advisory/Consultancy: Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, MSD; Advisory/Consultancy: BMS. W.M. Brueckl: Advisory/Consultancy: Roche; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/ Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, AstraZeneca. A. Bleckmann: Advisory/Consultancy: AstraZeneca. All other authors Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/ have declared no conflicts of interest. Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/ Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/ 83P Accommodation/Expenses: Siemens; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/ Evaluation of the prognostic significance of PD-L1 expression Accommodation/Expenses: Celgene; Honoraria (self), Advisory/Consultancy, after combined radiochemotherapy in patients with stage III Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/ Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Speaker NSCLC Bureau/Expert testimony, Research grant/Funding (institution), Travel/ Accommodation/Expenses: Takeda; Honoraria (self), Advisory/Consultancy, J. Wagner1, J. Roeper1, K. Willborn2, L.C. Heukamp3, F. Griesinger4 Speaker Bureau/Expert testimony, Research grant/Funding (institution): 1Pius Hospital Oldenburg, University of Oldenburg, Oldenburg, Germany; AbbVie. All other authors have declared no conflicts of interest. 2Pius Hospital, Oldenburg, Germany; 3Hematopathology Hamburg, Hamburg, Germany; 4Pius-Hospital Medical Campus, University of Oldenburg, Oldenburg, Germany 84P Background: The PACIFIC study showed that patients with locally Impact of PTV on progression-free survival in inoperable stage advanced, unresectable NSCLC after radio-chemotherapy derived a III non-small cell lung cancer patients treated with benefit in progression-free survival and overall survival when treated chemoradioimmunotherapy with durvalumab, a PD-L1-inhibitor vs. placebo. This effect was limited 1 1 1 1 ̈ 1 to patients with a PD-L1 expression of >1%. In patients with PD-L1 J. Taugner , M. Karin , L. Kaesmann , C. Eze , B. Florsch , 1 2 1 1 1 expression of <1%, no benefit was seen partly due to the fact that the J. Guggenberger , A. Tufman , C. Belka , F. Manapov Radiation outcome in the control arm was surprisingly favorable. Thus, it could be Oncology, Ludwig Maximilians University - Grosshadern, Munich, 2 ̈ speculated that lack of PD-L1 expression confers a favorable outcome Germany; LMU Klinikum der UniversitatMünchen, Munich, Germany after radio-chemotherapy in stage III NSCLC. To address the question, Background: Present study evaluates outcome after chemoradiotherapy whether the prolonged OS in the control group with lack of PD-L1 (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD- expression was reproducible we analyzed the OS in group of 101 patients 1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for with stage III NSCLC homogeneously treated with radio-chemotherapy inoperable stage III NSCLC patients depending on planning target and not progressing after radio-chemotherapy. PD-L1 expression was volume (PTV). S742 Journal of Thoracic Oncology Vol. 16 No. 4S

Methods: Prospective data of thirty-three consecutive patients with failure were detected in 4 (15%) and 2 (8%) patients, respectively. Three inoperable stage III NSCLC completed CRT with sequential Durvalumab (13%) patients presented with symptomatic relapse. (77%, 22 patients) or concurrent and sequential Nivolumab (33%, 11 Conclusions: Our prospective study confirmed a favourable safety patients) were analyzed. Different cut offs for PTV were evaluated for profile of durvalumab after completion of CRT in PD-L1 expressing association with progression-free (PFS) survival. inoperable NSCLC patients in a real-world setting. In a median follow-up Results: All patients were treated with conventionally fractionated TRT; time of 20.6 months, durvalumab was discontinued in 27% of all 93% to a total dose of at least 60 Gy (range: 60–63.6Gy). 97% of patients patients due to progressive disease. All patients with progressive disease received two cycles of concurrent platinum-based chemotherapy. were eligible for second-line treatment. Median follow-up for the entire cohort was 19.9 (range: 6.0–42.4) Legal entity responsible for the study: The authors. months; median overall survival (OS) was not reached. Median Funding: Has not received any funding. Progression-free survival (PFS) was 22.8 (95% CI: 10.7–34.8) months. Disclosure: F. Manapov: Research grant/Funding (Institution): AstraZeneca. All Patients with PTV ≥ 900ccm had a significantly shorter PFS (6.9 vs 22.8 other authors have declared no conflicts of interest. months, p = 0.020) and extracranial metastasis free survival (eMFS) (8.1 months vs not reached, p = 0.026). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (TNM 8th Ed.) achieved a dismal median 86P PFS of only 3.5 months (vs. 26.3 months p = 0.022). Post-operative radiotherapy (PORT) vs non-PORT in Conclusions: PTV has a significant impact on the PFS and eMFS after non-small cell lung cancer patients: A systematic review CRT combined with concurrent and/or sequential CPI in inoperable and meta-analysis stage III NSCLC. Patients with PTV ≥ 900ccm had a significantly shorter 1 1 1 1 PFS and eMFS. A. Hadisurya , F. Tandy , M. Suciningtias , R.S. Heriyanto , 1 1 1 1 Legal entity responsible for the study: The authors. C. Chrystelle , F. Wijovi , A. Tancherla , T.I. Hariyanto , 2 1 Funding: Has not received any funding. A. Kurniawan Faculty of Medicine, UPH - Pelita Harapan University - 2 Disclosure: F. Manapov: Research grant/Funding (Institution): AstraZeneca. Faculty of Medicine, Tangerang, Indonesia; Department of Internal All other authors have declared no conflicts of interest. Medicine, Pelita Harapan University, Tangerang, Indonesia Background: Non-small cell lung cancer (NSCLC) is the leading cause of death globally. At a certain stage, there is a risk of recurrence so 85P Post-operative Radiation (PORT) is needed. Based on available data, Real-world analysis of treatment patterns and efficacy of PORT is performed in patients with N2 after adjuvant chemotherapy or durvalumab maintenance after chemoradiotherapy in after surgery while taking neoadjuvant chemotherapy. However, several NSCLC patients studies showed that the survival of patients treated with and without PORT was not significantly different. This systematic review aims to 1 ̈ 1 1 2 3 J. Taugner ,L.Kasmann , C. Eze ,A.Rühle , A. Tufman , evaluate the survival rate of the PORT and Non-PORT group in NSCLC 4 4 1 1 1 N. Reinmuth , T.H-G-F. Duell , C. Belka , F. Manapov Radiation patients. Oncology, Ludwig Maximilians University - Grosshadern, Munich, Methods: We searched PubMed, PMC, Science Direct, Google Scholar, 2 Germany; Radiation Oncology, Uniklinikum Freiburg, Freiburg, Germany; and Europe PMC, on January 3rd, 2021 using a combination of keywords 3 4 LMU Klinikum der UniversitätMünchen, Munich, Germany; Thoracic associated with PORT and NSCLC concerning their survival rate based on Oncology, Asklepios-Fachklinikum, Gauting, Germany overall survival (OS). Publications included are limited to English manuscripts with observational design studies that were published in Background: Evaluation of clinical use and real-world efficacy of durvalumab maintenance treatment after chemoradiotherapy (CRT) in the past 10 years. Patients who received neoadjuvant chemotherapy or radiotherapy were excluded from this review. All included studies were inoperable non-small cell lung cancer (NSCLC). reviewed by all 9 authors. The quality of each included study were Methods: Patients with PD-L1 expressing NSCLC treated after October 2018 were included. Follow up including PET/CT and/or contrasted CT assessed using the Newcastle-Ottawa Scale (NOS) and GRADE. Results: We included a total of 20 studies consisting of 36.134 lung were performed every three months after CRT. Descriptive treatment pattern analyses, including reasons of discontinuation and salvage cancer patients. Based on NOS, 18 studies showed good quality while 2 treatment, were undertaken. Statistics were calculated from the last day others showed fair quality. Based on GRADE, these studies were moderate in quality as there was a largely consistent and precise of CRT. Results: Twenty-six patients with PD-L1 expressing unresectable NSCLC outcome with publication bias. The association of PORT and OS were found in all included studies. Sixteen studies showed that PORT were included. Median follow up achieved 20.6 months (range:1.9– improved patients’ overall survival with NSCLC. However, four studies 30.6). Durvalumab was initiated after a median of 25 (range: 13–103) days after completion of CRT. In median 14 (range: 2–24) cycles of showed that there were no significant differences in OS between the PORT and Non-PORT group. Pooled analysis showed that statistically durvalumab were applied within 6.4 (range 1–12.7) months. Six patients – (23%) are still in treatment and seven (27%) have completed treatment PORT is associated with better OS (HR = 0.90; 95% CI, 0.83 0.99; p = 0.0005) when compared with Non-PORT and clinically, PORT showed no with 24 cycles. Maintenance treatment was discontinued in 13 (50%) significant result. patients: 4 (15%) patients developed grade 3 pneumonitis (CTCAE v5) after a median of 3.9 (range: 0.5–11.6) months and 7 (range: 2–17) Conclusions: There is no significant difference between PORT and OS from the collected studies since those studies are observational. Further cycles of durvalumab. Four (15%) patients developed grade 2 skin toxicity. One (4%) patient has discontinued treatment due to incom- clinical trial studies regarding PORT and OS are still needed to confirm the result. pliance. Six and 12- month progression-free survival (PFS) rates were Legal entity responsible for the study: Audrey Hadisurya. 82% and 62%, median PFS was not reached. No case of hyperprogression was documented. Eight (31%) patients have relapsed during Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest. maintenance treatment after a median of 4.8 (range: 2.2–11.3) months and 11 (range: 6–17) durvalumab cycles. Two patients (9%) developed a local-regional recurrence after 14 and 17 cycles of durvalumab. Extracranial distant metastases and brain metastases as first site of April 2021 Abstracts S743

been shown to improve ORR, PFS and OS in the metastatic setting. 87P Induction therapy with chemotherapy with or without radiotherapy is Impact of chemoradiotherapy on the survival of patients with an established approach in stages II and III, however no data exist for stage III NSCLC induction therapy with TKI and chemotherapy in EGFR mt+ NSCLC. Here we describe the outcome of 10 pts with EGFR mt+ NSCLC, all stage III, st rd R. Basto, J. Correia Magalhães, M.J.P. de Sousa, J.C. Monteiro, treated with 1 and 3 generation TKI in combination with I. Domingues, E. Jesus, G. Sousa Medical Oncology Department, chemotherapy as induction therapy. Instituto Portugues Oncologia de Coimbra Francisco Gentil E. P. E. (IPO Methods: 10/10 pts had adenocarcinoma, 6 with EGFR exon 19 and 4 Coimbra), Coimbra, Portugal. with EGFR L858R. Pts received erlotinib (n = 2), gefitinib (n = 5) or osimertinib (n = 3) for 10 days followed by TKI in combination with Background: Stage III NSCLC represents a heterogeneous group of chemotherapy (taxane /cisplatin (n = 5), paclitaxel/carboplatin (n = 5)) patients (pts). The treatment of such pts may be a challenge, requiring a for 3 cycles. RECIST radiologic response as well as regression grading multimodal approach and the need to adapt the treatment to the disease according to Junker et al. was performed on the resection specimens. and the patient. Definitive cure rates, as well as long-term prognosis Results: 7 pts are evaluable for response, 3 patients treated with differ significantly between the sub-stages. osimertinib are still on therapy. 7/7 pts achieved radiologic PR after 2 Methods: This retrospective study has as primary endpoint the cycles, all tumors were R0 resected. pCR was achieved in the primary evaluation of the impact of concomitant chemoradiotherapy (ChR) and tumor in 2/7 evaluable pts, 5/7 pts did not achieve pCR or MPR in the concomitant ChR at day 50 (chemoradiotherapy (Ch) starts D1 and primary tumor. In the mediastinal lymph nodes, MPR was achieved in 6/ radiotherapy starts concomitantly with Ch at D50) (ChR50) in the 7 evaluable pts (1 pCR). 2 patients achieving pCR in the primary tumor, 5 survival of stage III NSCLC pts. The secondary endpoint is to assess pts relapsed at 8 to 17 (median 12) months, 3/5 with CNS as 1st relapse survival by age group. The data were collected and analyzed using the site and 2/5 with other sites. With a median follow up of 46 months (13– software “IBM SPSS”® v25. 68), 6 pts are alive at 2+, 2+, 2+, 13+, 44+, 67+ months and one patient Results: From January 2017 to December 2020, 66pts were eligible died in CR of secondary cancer at 51 months. Median OS of the 10 pts as they underwent ChR (n = 30) or ChR50 (n = 36). In this sample: was 51 months and mPFS was 17 months. Further data with respect to 72.7% (n = 48) were male; median age at diagnosis was 66 years (yrs); osimertinib + chemotherapy induction will be presented at the meeting. 53% (n = 35) had ECOG-PS of 0; 37.9% (n = 25) were active smokers; Conclusions: In conclusion 1st and 3rd generation TKI-chemotherapy 51.4% (n = 34) of the tumors were adenocarcinoma (ADC); 50% (n = induction in EGFR mt+ NSCLC is feasible, leads to high MPR rates in 33) were stage IIIB (AJCC 7th edition) and PDL1 expression was positive mediastinal lymph nodes and lower pathologic response rates in the in 32 pts. In this study, 52pts had a disease progression, 25pts treated primary tumors. pCR in the primary tumor may predict better outcome. with ChR and 27pts treated with ChR50 (4-year follow-up). PFS As CNS is the most frequent site of relapse this site might be of special was 13.92mos in the ChR group and 12.70mos in the ChR50 group interest in further induction studies on EGFR mt+ NSCLC, including (p value = 0.014); PFS was 10.8mos in the group <65yrs (n = 23) and NeoADAURA study. 15.2mos in the group ≥ 65yrs (n = 29) (p value = 0.226); ADC showed Legal entity responsible for the study: University Hospital Internal higher PFS than SCC (17 vs 9.5mos) (p value = 0.059). The mortality rate Medicine-Oncology, Pius Hospital Oldenburg, University Oldenburg. in this study was 50% (n = 33), 20pts treated with ChR and 13pts treated Funding: Has not received any funding. with ChR50(4-year follow-up). OSwas not influenced by the administered Disclosure: F. Griesinger: Honoraria (self), Advisory/Consultancy, Speaker scheme. OS was 13.6mos in the group <65yrs and 15.1mos in the group ≥ Bureau/Expert testimony, Research grant/Funding (institution), Travel/ 65yrs (p value = 0.211). Histology, age, smoking habits, PDL1, ECOG-PS Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/ Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institu- and stage did not show SS in their relationship with PFS and OS. tion), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/ Conclusions: PFS was influenced by the treatment (ChR) instituted and Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institu- this result was independent of age, smoking habits, PDL1, ECOG-PS and tion), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/ stage. PFS was higher in the group ≥ 65yrs, although it is a trend that Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/ cannot be assumed due to the small sample size. PFS was higher in the Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institu- group ≥ 65yrs, although it is a trend that cannot be assumed due to the tion), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/ small sample size. Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institu- Legal entity responsible for the study: The authors. tion), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/ Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institu- Funding: Has not received any funding. tion), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/ Disclosure: All authors have declared no conflicts of interest. Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Siemens; Honoraria (self), Advisory/ Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Honoraria (self), Advisory/ 88P Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institu- Curative treatment in EGFR mt+ NSCLC stage III by induction tion), Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/ Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institu- TKI-chemotherapy combination: Feasibility and outcome in tion), Travel/Accommodation/Expenses: Takeda; Honoraria (self), Advisory/ 10 cases Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AbbVie. J. Roeper: Honoraria (self): Boehringer Ingelheim; Honoraria (self): 1 2 3 3 3 AstraZeneca; Honoraria (self): Roche. M. Sebastian: Honoraria (self), Advisory/ F. Griesinger , J. Roeper , K. Willborn , R. Prenzel , D. Scriba , Consultancy: Sanofi; Honoraria (self): Boehringer Ingelheim; Honoraria (self): M. Sebastian4 1Pius Hospital Oldenburg, University of Oldenburg, Tesaro; Honoraria (self): Amgen; Honoraria (self): Pfizer; Honoraria (self): Lilly; Oldenburg, Germany; 2Department of Internal Medicine-Oncology, Pius Honoraria (self): Roche; Honoraria (self): Takeda; Honoraria (self): BionTech; Hospital, Oldenburg, Germany; 3Pius Hospital, Oldenburg, Germany; Honoraria (self): Novartis; Honoraria (self): CuraVec. All other authors have declared no conflicts of interest. 4Department of Hematology/Medical Oncology, Universitätsklinikum Frankfurt (Johannes-Wolfgang Goethe Institute), Frankfurt am Main, Germany

Background: EGFR TKI’s are a mainstay in the treatment of metastatic NSCLC with EGFR mt+, however their use in the curative setting is not yet standard of care. Recently, combination of TKI and chemotherapy has S744 Journal of Thoracic Oncology Vol. 16 No. 4S

89P 90P Long-term clinical outcomes and prognostic factors of upfront Salvage radiotherapy for locoregional recurrence after lung surgery as a first-line therapy in pathological N2 NSCLC cancer resection: A UK cohort

L. Bertolaccini, E. Prisciandaro, G. Sedda, L. Girelli, L. Spaggiari R. Li, H. Ariyaratne Department of Oncology, Royal Free London NHS Thoracic Surgery, IEO European Institute of Oncology IRCCS, Milan, Italy. Foundation Trust, London, UK Background: Multimodality therapy offers the best opportunity to Background: Retrospective studies have shown good clinical outcomes improve the prognosis of pathologic N2 (pN2) NSCLC. Upfront surgery with 3D-conformal radiotherapy (RT) for locoregional recurrence of followed by adjuvant therapy is currently performed in resectable N2 non-small cell lung cancer (NSCLC). We investigated the outcomes of NSCLC. Aim: To evaluate long-term clinical outcomes and prognostic patients given salvage thoracic treatment using intensity-modulated factors of upfront surgery as first-line therapy in pN2. radiotherapy (IMRT) in our institution. Methods: Retrospective review of pN2 NSCLC (2007–2017). Exclusion Methods: We retrospectively reviewed all patients treated with radical criteria: other malignancies; incomplete surgical resections; incomplete RT or chemoradiotherapy (CRT) at the Royal Free Hospital for data. The preoperative staging was performed according to well- locoregional recurrence of NSCLC between November 2016 and established/widely accepted protocols. The multidisciplinary team November 2019. All patients had FDG-PET staging prior to surgery determined treatment strategies for biopsy-proven N2. Upfront- and at time of recurrence. surgery was considered if primary tumour was resectable, with single- Results: 14 patients were identified with a median age of 68 years station mediastinal nodal metastases, no evidence of extra-nodal (range 55–78 years). The most common histological type was invasion. OS/DFS were estimated using Kaplan–Meier. Cox hazards adenocarcinoma (71%). All patients had lobectomy, and the median model was used for univariable/multivariable analyses. time to recurrence from surgery was 16 months (range 3–48 months). Results: 285 R0 resections were included; 159 (55.8%) patients All patients had nodal recurrence, with 50% having multiple station received induction chemotherapy. recurrence. 9 patients received concurrent CRT, 1 received sequential Univariable/multivariable Cox analyses showed that older age and CRT and 4 received RT alone. Most patients had low-volume recurrence comorbidities were significantly associated with worse OS. Mean follow- with a median GTV volume of 19 cm3 (range 4–89 cm3). All patients were up time was 39.6 ± 24.7 months. At follow-up-end, 127 (44.6%) had treated with volumetric modulated arc IMRT. Patients receiving died. For the induction chemotherapy group, the median OS was 49 sequential CRT or RT alone received 55Gy in 20 fractions. Patients months (95%CI: 38–70 months) and 5-year OS was 44.4%. Median and who received concurrent CRT were treated with 60–66 Gy in 30–33 5-year OS for upfront surgery group were 66 months (95%CI: 40–119) fractions with cisplatin-vinorelbine. Only one patient experienced grade and 66.3%, respectively. There were no statistically significant differ- 3 toxicity requiring hospital admission for dehydration. Median follow- ences between treatments(p = 0.48). 137 (48.1%) developed recur- up was 16 months (range 6–44 months). 12-month overall survival was rence. 5-years DFS was 17% (95%CI: 11–25) for induction 86%. The sample was not large enough to detect any significant chemotherapy and 22% (95%CI: 9–32%) for upfront surgery; there correlates with prognostic factors. were no statistically significant differences (p = 0.93). Based on cN, no Conclusions: Excellent early survival outcomes and low toxicity were significant differences were observed (OS, p = 0.36/DFS, p = 0.65). seen with salvage IMRT for nodal recurrence of NSCLC after lobectomy. A larger sample size would be needed to assess prognostic factors and Table 89P compare the outcomes from CRT and RT alone. Legal entity responsible for the study: The authors. Induction Chemotherapy Upfront Surgery p-value Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest. Age 62.7 ± 9.0 66.3 ± 8.3 0.58 M/F Ratio 1.9 1.7 0.74 Comorbidities Cardiac 66 (41.5) 73 (57.9) 20 (15.9) 0.51 Pulmonary 14 (8.8) 91P FEV1% DLCO/VA% 88.1 ± 18.9 93.5 ± 20.3 0.96 The role of endobronchial ultrasound guided transbronchial 82.9 ± 20.6 90.4 ± 20.7 needle aspiration (EBUS-TBNA) in the diagnosis of large cell Adenocarcinoma 120 (75.5) 31 105 (83.3) 16 (12.7) 0.54 Squamous cell Other (19.5) 8 (5.0) 5 (4.0) neuroendocrine carcinoma (LCNEC) Open VATS Robot 155 (97.5) 100 (79.4) 11 (8.7) 0.026 1 1 2 2 2 1 4 (2.5) 15 (11.9) B. Teng , M. Rice , D. Rana , D. Shelton , N. Narine , H.M. Al-Najjar Segmentectomy 2 (1.3) 88 3 (2.4) 93 (73.8) 0.0038 1Respiratory, Manchester University Foundation Trust, Manchester, UK; Lobectomy Bilobectomy (55.3) 13 (8.2) 7 (5.6) 23 (18.2) 2Pathology, Manchester University Foundation Trust, Manchester, UK Pneumonectomy 56 (35.2) Complications 75 (47.2) 41 (32.5) 0.74 Background: LCNEC are rare pulmonary tumours conferring a poor prognosis. Achieving a pathological diagnosis is challenging, often ultimately made on resected surgical specimens. We hypothesise that Conclusions: Upfront surgery as first-line therapy in pN2 NSCLC EBUS-TBNA can provide cytology in a minimally invasive procedure on showed favourable clinical outcomes. Therefore, it should be considered which diagnosis can be achieved, allowing treatment planning. as a treatments option in resectable N2 NSCLC. Methods: A review of a prospectively maintained EBUS database Legal entity responsible for the study: The authors. between January 2014 and December 2019 in our institute was Funding: Has not received any funding. conducted to identify all those with a final cytological diagnosis of NSCLC with NE morphology. All procedures utilised Rapid On-Site Disclosure: All authors have declared no conflicts of interest. Evaluation (ROSE) by a consultant cytopathologist. Diagnoses of small cell carcinoma and low-grade neuroendocrine tumours were excluded. Pathological diagnoses were made according to IASLC/ATS/ERS criteria. Results: A total of 2456 patients underwent EBUS at our institute in the study period. 35 possible LCNEC patients were identified, age range 40– April 2021 Abstracts S745

89 years (mean 69). Of these 31 had a final cytological diagnosis of NSCLC with NE morphology (NE markers positive), 3 of which had a 93TiP small cell carcinoma component. Four of the 35 cases had negative NE MERMAID-2: Phase III study of durvalumab in patients with markers but were clinically considered to be LCNEC. At ROSE, the resected, stage II-III NSCLC who become MRD+ after cases were called carcinoma (n = 13), NSCLC (n = 14), small cell curative-intent therapy carcinoma (n = 5), NE carcinoma (n = 2) and no malignant cells (n = 1). Of 5 cases called small cell carcinoma at ROSE, 4 had positive NE D.R. Spigel1, S. Peters2, M-J. Ahn3, M. Tsuboi4, J. Chaft5, D. Harpole6, markers. LCNEC EBUS samples were either from the primary lesion (n = F. Barlesi7, C. Abbosh8, H. Mann9,R.May10, P.A. Dennis10, 2) or from mediastinal/hilar lymph nodes (n = 33). Most LCNEC cases C. Swanton11 1Sarah Cannon Research Institute/Tennessee Oncology, were advanced with 17/35 at stage III disease and 13/35 presenting at Nashville, TN, USA; 2Centre Hospitalier Universitaire Vaudois, Lausanne, stage IV and the remainder (5/35) stage I and II. Three patients had Switzerland; 3Sungkyunkwan University School of Medicine, Seoul, further histological confirmation from other sites (ultrasound guided Republic of Korea; 4Division of Thoracic Surgery and Oncology National biopsy of primary lesion and two post-operative surgical specimens) Cancer Center Hospital East, Kashiwa, Japan; 5Memorial Sloan Kettering corroborating the diagnosis. Cancer Center, New York, NY, USA; 6Duke University Medical Center, Conclusions: All our cases with further histology sampling were Durham, NC, USA; 7Gustave Roussy Cancer Campus, Villejuif, France; confirmed LCNEC. As most of our patients presented with advanced 8Cancer Research UK Lung Cancer Centre, University College London disease, the majority had no histological confirmation, making definite Cancer Institute, London, UK; 9AstraZeneca, Cambridge, MD, UK; conclusions on the specificity and sensitivity of cytology alone difficult. 10AstraZeneca, Gaithersburg, MD, USA; 11The Francis Crick Institute/ Overall, we have demonstrated that EBUS-TBNA is a suitable method to Cancer Research UK Lung Cancer Centre, University College London provide material to make an initial diagnosis of LCNEC. Cancer Institute/University College London Hospitals Foundation Trust, Legal entity responsible for the study: The authors. London, UK Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest. Background: In patients with resected, stage II-III NSCLC, the 5-year disease-free survival (DFS) rate with SoC adjuvant chemotherapy is ∼40%. Despite advances with immunotherapy (IO) in the metastatic 92P setting, overall survival (OS) rates for patients with recurrence remain Neuroimaging in staging patients for curative intent stage II low. Detection of minimal residual disease (MRD), as indicated by and III non-small cell lung cancer circulating tumor DNA (ctDNA), may indicate the presence of clinically indiscernible residual tumor following curative-intent therapy and enable earlier therapeutic intervention, thereby improving outcomes in S.A. Growcott1, J. Page2, S. Foster2, J. Walther1 1Oncology, Musgrove patients at highest risk of recurrence. In the phase III PACIFIC trial, Park Hospital - Taunton and Somerset NHS Foundation Trust, Taunton, consolidation durvalumab improved survival outcomes in patients with UK; 2Respiratory, Musgrove Park Hospital - Taunton and Somerset NHS unresectable, stage III NSCLC without detectable disease progression Foundation Trust, Taunton, UK after curative-intent chemoradiotherapy (Antonia, 2018), suggesting Background: Approximately 10% of patients with newly diagnosed MRD is vulnerable to additional therapy, particularly IO, a concept non-small cell lung cancer (NSCLC) will have brain metastases. National supported by recent data in MRD+ patients (Moding, 2020). MERMAID-2 Institute for Health Care Excellence (NICE) recommends that patients will assess the efficacy and safety of durvalumab, versus placebo, in with curative intent stage II and III NSCLC should have pre-treatment CT patients with resected, stage II-III NSCLC who become MRD+ after or MRI head, respectively. Early detection and management of brain curative-intent therapy. metastases may slow disease progression and increase survival. Trial design: MERMAID-2 (NCT04642469) is a global, phase III, double- Methods: Patients diagnosed with NSCLC between January 2019 and blind multicenter study that is currently recruiting patients. Patients October 2020 were reviewed. The local imaging portal was used to with histologically confirmed EGFR/ALK wild-type stage II-III NSCLC review neuroimaging. Two PDSA cycles were completed following who have completed curative-intent therapy (complete resection + baseline audit. These included presenting results at Lung MDT and optional neoadjuvant and/or adjuvant therapy) will be enrolled in a 96- creating a prompt on the Lung MDT list to remind clinicians to request week surveillance period. During this period, patients will be monitored appropriate neuroimaging. regularly for MRD emergence via ctDNA analysis of plasma samples, Results: 44 patients diagnosed with curative intent stage II and III based on personalized MRD panels. Patients who become MRD+ during NSCLC between January 2019 to October 2020 were audited for pre- the surveillance period will be further evaluated to confirm eligibility treatment neuroimaging. At baseline, correct neuroimaging was (no disease recurrence visible on imaging; known PD-L1 status) and performed in 40% of patients with stage II and III disease. Incorrect ∼284 MRD+ patients will be randomized 1:1 to receive durvalumab imaging was performed in 0% stage II and 20% stage III disease. No 1500 mg IV or placebo q4w, up to 24 months or until investigator- neuroimaging was performed in 60% stage II and 40% stage III patients. assessed disease recurrence. The primary endpoint is DFS in patients Following 2 PDSA cycles, correct neuroimaging was obtained in 33.3% with PD–L1 tumor cell expression ≥1%. Secondary endpoints include stage II and 72.7% stage III disease. Incorrect imaging was performed in DFS in the full analysis set, progression-free survival, OS, time to 0% stage II and 9% stage III disease. No neuroimaging was performed in subsequent therapy, patient-reported outcomes, and safety. 66.7% stage II and 18.2% stage III patients. Clinical trial identification: NCT04642469. Conclusions: Significant improvement has been demonstrated in Editorial acknowledgement: Medical writing support, which was in neuroimaging for stage III disease. However, increasing compliance for accordance with Good Publication Practice (GPP3) guidelines, was stage II has been more challenging. We feel our experience should provided by Andrew Gannon and Connor Keating of Cirrus prompt all centres to audit this practice, as despite clinicians’ belief that Communications (New York, NY), an Ashfield company, and was these investigations were being done appropriately, the figures do not funded by AstraZeneca. support this and interventions were necessary. We have since Legal entity responsible for the study: AstraZeneca. implemented a third intervention and a re-audit is planned in 6 months. Funding: AstraZeneca. Legal entity responsible for the study: The authors. Disclosure: D.R. Spigel: Research grant/Funding (institution), Conduct of Funding: Has not received any funding. clinical trials and consultancy: AstraZeneca/BMS/Celgene/EMD Serono/Roche/ Genetech/GSK/Ipsen/ Novartis/Takeda; Research grant/Funding (institution), Disclosure: All authors have declared no conflicts of interest. Conduct of clinical trials: Aeglea Biotherapeutics/Agios/Astellas Pharma/ S746 Journal of Thoracic Oncology Vol. 16 No. 4S

BIND Therapeutics/Celldex Therapeutics/Clovis/ Daiichi Sankyo/Eisai/Eli Lilly/ DT23–17). Stand Up To Cancer is a programme of the Entertainment Industry G1 Therapeutics/GRAIL; Research grant/Funding (institution), Conduct of clinical Foundation. Research grants are administered by the American Association for trials: ImClone Systems/Janssen/MedImmune/Merck/ Nektar Therapeutics/ Cancer Research, the Scientific Partner of SU2C. Charles Swanton also receives Neon Therapeutics/Tesaro/ Transgene/UT Southwestern/Cyteir Therapeutics/ funding from the European Research Council (ERC) under the European Union’s Apollomics/Elevation Oncology; Research grant/Funding (institution), Payment to Seventh Framework Programme (FP7/2007–2013) Consolidator Grant (FP7- institution for consulting services: Aptitude Health/Bayer/Dracen THESEUS-617844), European Commission ITN (FP7-PloidyNet 607722), an ERC Pharmaceuticals/Exelixis/Iksuda Therapeutics/ Intellisphere/ Jazz Advanced Grant (PROTEUS) from the European Research Council under the Pharmaceuticals/ Mirati Therapeutics/ Molecular Templates /Puma European Union’s Horizon 2020 research and innovation programme (835297) Biotechnology. S. Peters: Advisory/Consultancy, Personal fees (advisory board and Chromavision from the European Union’s Horizon 2020 research and and honorarium): AbbVie/Amgen/AstraZeneca/Bayer/Biocartis/Boehringer innovation programme (665233). All other authors have declared no conflicts of Ingelheim/Bristol-Myers Squibb/Clovis/Daiichi Sankyo/ Debiopharm/Eli Lilly/F, interest. Hoffman-La Roche/Foundation Medicine/Illumina/Janssen/MSD/Merck Serono/ Merrimack/Novartis; Advisory/Consultancy, Personal fees (advisory board and honorarium): Pharma Mar/ Pfizer/Regeneron/Bioinvent/Sanofi/Seattle Genetics and Takeda; Speaker Bureau/Expert testimony, Personal fees (talks and 94TiP honorarium): AstraZeneca/Boehringer Ingelheim/ Bristol-Myers Squibb/Eli Lilly/F. Hoffmann la Roche/MSD/Novartis/Pfizer/Takeda/Sanofi; Research Neoadjuvant tislelizumab or placebo + platinum-based grant/Funding (self), Non-financial support for clinical trial investigation: chemotherapy followed by adjuvant tislelizumab or placebo Amgen/AstraZeneca/Boehringer Ingelheim/ Bristol-Myers Squibb/Clovis/F. in patients with resectable non-small cell lung cancer Hoffmann-La Roche/Illumina/MSD/Merck Serono/Novartis /Pfizer. M. Tsuboi: Advisory/Consultancy, Personal fees for advisory boards and lectures: (NSCLC): A phase III trial in progress AstraZeneca KK/Chugai Pharmaceutical/MSD; Advisory/Consultancy, Personal fees for advisory boards: Novartis; Research grant/Funding (self), Personal fees C. Wang1, R. Wang2,Y.Ma2, X. Liang2 1Tianjin Medical University for lectures: Medtronic Japan/ONO Pharmaceutical/Johnson & Johnson Japan/Eli Cancer Institute & Hospital, Tianjin, China; 2BeiGene (Shanghai) Co., Ltd., Lilly Japan/Bristol-Myers Squibb KK/Teijin Pharma/Taiho Pharma; Research grant/Funding (institution), Research funding: Boehringer Ingelheim Japan; Shanghai, China Research grant/Funding (institution), Commissioned research for clinical trials: MSD/AstraZeneca KK/ONO Pharmaceutical/ Bristol-Myers Squibb KK/Eli Lilly Background: Adjuvant and neoadjuvant therapies have been proposed Japan. J. Chaft: Advisory/Consultancy: AstraZeneca/Bristol-Myers Squibb/ to improve the prognosis of patients (pts) with stage II/IIIA lung cancer Genentech/Flame Biosciences/Merck. D. Harpole: Speaker Bureau/Expert testi- but have provided only modest survival benefits. When added to mony: AstraZeneca; Advisory/Consultancy: AstraZeneca/Medtronic. F. Barlesi: chemotherapy, PD-(L)1 inhibitors have resulted in enhanced antitumor Research grant/Funding (self), Personal fees: AstraZeneca/Bayer/Bristol-Myers Squibb/Boehringer Ingelheim/Eli Lilly Oncology; Research grant/Funding (self), activity versus chemotherapy alone, but their ability to limit relapse in Personal fees: F. Hoffmann–La Roche Ltd/Novartis/Merc/MSD/Pierre Fabre/ pts who have undergone surgical resection has not yet been fully Pfizer/Takeda. C. Abbosh: Advisory/Consultancy: AstraZeneca; Speaker Bureau/ elucidated. Tislelizumab, a monoclonal antibody with high affinity Expert testimony: Bristol-Myers Squibb; Research grant/Funding (self), and specificity for PD-1, was engineered to minimize binding to FcγRon Contracted/support research grant: AstraZeneca; Research grant/Funding (institution), Current AstraZeneca Physician Fellow (grant to University College macrophages to abrogate antibody-dependent phagocytosis. London): AstraZeneca; Licensing/Royalties, Royalty/intellectual property/patent Tislelizumab, as a single agent and in combination with chemotherapy, holder - author on two pending patents: AstraZeneca. H. Mann: Full/Part-time has demonstrated a manageable tolerability profile and efficacy in pts employment: AstraZeneca. R. May: Full/Part-time employment: AstraZeneca. P.A. with advanced NSCLC. Dennis: Full/Part-time employment: AstraZeneca; Shareholder/Stockholder/ Stock options: AstraZeneca. C. Swanton: Honoraria (self), Research grant/ Trial design: This phase III, randomized, double-blind study Funding (self), Chief Investigator for the MeRmaiD1 clinical trial: AstraZeneca; (NCT04379635) compares the efficacy of neoadjuvant tislelizumab or Advisory/Consultancy, Chief Investigator for the MeRmaiD1 clinical trial: placebo + platinum-based doublet chemotherapy followed by adjuvant AstraZeneca; Honoraria (self), Research grant/Funding (self): Bristol-Myers tislelizumab or placebo. Adult pts (n≈380) with histologically con- Squibb; Honoraria (self), Research grant/Funding (self): Pfizer; Honoraria (self), Research grant/Funding (self): Roche-Ventana; Honoraria (self), Research firmed, squamous (sq) or nonsquamous (nsq) stage II/IIIA resectable grant/Funding (self): Ono Pharmaceutical; Research grant/Funding (self), NSCLC are eligible; key exclusion criteria include prior systemic collaboration in minimal residual disease sequencing technologies: Archer Dx anticancer treatment for lung cancer or known EGFR mutations or Inc; Research grant/Funding (self): Boehringer Ingelheim; Honoraria (self): ALK rearrangements. In the neoadjuvant phase, pts will be randomized Novartis; Honoraria (self): GSK; Honoraria (self): Celgene; Honoraria (self): MSD; Honoraria (self): Illumina; Honoraria (self): Genentech; Honoraria (self): Sarah 1:1 to receive tislelizumab (Arm A) or placebo (Arm B) plus cisplatin/ Cannon Research Institute; Honoraria (self): Medixci; Honoraria (self): Bicycle carboplatin + paclitaxel or pemetrexed on Day 1 of each 3-wk cycle for 3– Therapeutics; Shareholder/Stockholder/Stock options: GRAIL; Shareholder/ 4 cycles. Patients will be stratified by histology (sq vs nsq), disease stage Stockholder/Stock options: Apogen Biotechnologies; Shareholder/Stockholder/ (II vs IIIA), and PD-L1 expression (≥1% vs <1%). After surgery, adjuvant Stock options: Epic Biosciences; Honoraria (self), Shareholder/Stockholder/Stock options: Achilles Therapeutics; Intellectual property [patents issued]: Assay therapy (tislelizumab [A]; placebo [B]) will be administered on Day 1 of technology to detect tumour recurrence (PCT/GB2017/053289), Targeting each 6-wk cycle for up to eight cycles. Major pathological response rate neoantigens (PCT/EP2016/059401), Identifying patient response to immune (proportion of pts with ≤10% residual viable tumors) and event-free checkpoint blockade (PCT/EP2016/071471), Determining HLA LOH (PCT/ survival per RECIST v1.1 are dual primary endpoints. Secondary GB2018/052004), Predicting survival rates of patients with cancer (PCT/ GB2020/050221), Identifying patients who respond to cancer treatment (PCT/ endpoints include overall survival, objective response rate, disease- GB2018/051912), Detecting tumour mutations (PCT/US2017/28013), Insertion/ free survival, pathological complete response rate, safety/tolerability deletion mutation targets (PCT/GB2018/051892); Other: Charles Swanton is (assessed by monitoring incidence and severity of adverse events), and Royal Society Napier Research Professor (RP150154). His work is supported by health-related quality-of-life measures. the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001169), the UK Medical Research Council (FC001169) and the Wellcome Clinical trial identification: NCT04379635. Trust (FC001169). For the purpose of Open Access, the author has applied a CC BY Editorial acknowledgement: Writing and editorial assistance was public copyright licence to any Author Accepted Manuscript version arising from provided by Stephan Lindsey, PhD, and Elizabeth Hermans, PhD (OPEN this submission. Charles Swanton is funded by Cancer Research UK (TRACERx, Health Medical Communications, Chicago, IL), and funded by the study PEACE and CRUK Cancer Immunotherapy Catalyst Network), Cancer Research UK Lung Cancer Centre of Excellence, the Rosetrees Trust, Butterfield and Stoneygate sponsor. Trusts, NovoNordisk Foundation (ID16584), Royal Society Research Professorship Legal entity responsible for the study: BeiGene, Ltd. Enhancement Award (RP/EA/180007), the NIHR BRC at University College Funding: BeiGene, Ltd. London Hospitals, the CRUK-UCL Centre, Experimental Cancer Medicine Centre Disclosure: R. Wang: Full/Part-time employment: BeiGene, Ltd. Y. Ma: Full/Part- and the Breast Cancer Research Foundation, USA (BCRF). His research is time employment: BeiGene, Ltd. X. Liang: Full/Part-time employment: BeiGene, supported by a Stand Up To Cancer-LUNGevity-American Lung Association Lung Ltd. All other authors have declared no conflicts of interest. Cancer Interception Dream Team Translational Research Grant (SU2C-AACR- April 2021 Abstracts S747

Trial design: DUART (NCT04249362) is a phase II, open-label, single- 95TiP arm, multicenter, international study enrolling pts aged ≥18 years with DUART: A phase II study of durvalumab following radiotherapy histologically/cytologically confirmed unresectable, Stage III NSCLC, in patients with unresectable, stage III NSCLC ineligible for deemed ineligible for CT by investigator/physician criteria, with no PD – ≤ chemotherapy following RT (40 66 Gy; completed 42 days prior to receiving durvalumab), who have not received prior immunotherapy, and with ECOG PS ≤2. About 150 pts will be enrolled into 2 cohorts (1:1) A.R. Filippi1, R. Dziadziuszko2, M.R. Garcia Campelo3, J-B. Paoli4, according to prior RT dose delivered in enrolling centres (A: standard W. Sawyer5, I.E. Dıaź Pérez6 1Department of Radiation Oncology, RT, 60 Gy ± 10% or hypofractionated bioequivalent dose [BED]; B: Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, palliative RT, 40 to <54 Gy or hypofractionated BED). Pts will receive Italy; 2Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, 1500 mg durvalumab iv every 4 weeks for up to 12 months or until PD Poland; 3Medical Oncology Unit, University Hospital A Coruña, A Coruña, or unacceptable toxicity. The primary endpoint is safety and tolerability, Spain; 4Medical Oncology and Radiotherapy, Hôpital Saint Joseph, defined by incidence of grade 3/4 adverse events possibly related to Marseille, France; 5AstraZeneca, Cambridge, UK; 6AstraZeneca, treatment within 6 months of first dose. Secondary efficacy endpoints Gaithersburg, MD, USA include PFS, OS, objective response rate and duration of response. Background: About 30% of pts with NSCLC present with Stage III Clinical trial identification: NCT04249362. disease; most pts are deemed inoperable. In the phase III PACIFIC trial, Editorial acknowledgement: Medical writing support, which was in durvalumab, a selective, high–affinity, human IgG1 monoclonal antibody accordance with Good Publication Practice (GPP3) guidelines, was that blocks PD-L1 binding to PD-1 and CD80, significantly improved provided by Connor Keating of Cirrus Communications (Macclesfield, progression-free and overall survival (PFS/OS) in pts with unresectable, UK), an Ashfield company, and was funded by AstraZeneca. Stage III NSCLC without disease progression (PD) after ≥2 cycles of Legal entity responsible for the study: AstraZeneca plc. platinum-based concurrent chemoradiotherapy (cCRT). Consequently, Funding: AstraZeneca. the ‘PACIFIC regimen’ is now standard of care in this setting for pts with Disclosure: A.R. Filippi: Non-remunerated activity/ies, Non-financial support: good performance status (PS). Pts with poor PS, comorbidities, or AstraZeneca; Advisory/Consultancy, Advisory board: AstraZeneca/Roche; Speaker Bureau/Expert testimony, Speaker’s bureau: MSD/Ipsen. R. Dziadziuszko: Non- advanced age (a large proportion of this population) may be ineligible remunerated activity/ies, Non-financial support: AstraZeneca/Roche; Research for chemotherapy (CT) due to expected high toxicity. These pts typically grant/Funding (self), Personal fees: AstraZeneca/Roche; Research grant/Funding receive definitive radiotherapy (RT) alone, with poor survival rates (3- (self), Personal fees: Foundation Medicine/Seattle Genetics/Takeda/Boehringer year: 5–10%). Based on the PACIFIC trial data and the strong biological Ingelheim/Novartis/MSD/Pfizer/Regeneron. M.R. Garcia Campelo: Research grant/Funding (self), Personal fees: AstraZeneca/Roche/Lilly/Novartis/MSD/ rationale for combining RT with anti-PD-L1 consolidation therapy, Takeda/Pfizer. J-B. Paoli: Research grant/Funding (self), Personal fees relating durvalumab following RT could provide additional survival benefit vs to clinical trials in lung/renal/bladder/prostate cancer: MSD/Bristol-Myers RT alone in these pts. The DUART study will assess safety and Squibb/Pfizer/Janssen. W. Sawyer: Full/Part-time employment, Contractor: ́ ́ tolerability of durvalumab following RT in pts with unresectable, Stage AstraZeneca. I.E. Dıaz Perez: Full/Part-time employment: AstraZeneca; Shareholder/Stockholder/Stock options: AstraZeneca. III NSCLC ineligible for CT. ABSTRACTS

Disclosure: C. Zhou: Honoraria (self ): Roche; Honoraria (self ): Lily China; ADVANCED NSCLC Honoraria (self ): Boehringer Ingelheim; Honoraria (self ): Merck; Honoraria (self ), Advisory/Consultancy: Hengrui; Honoraria (self ), Advisory/Consultancy: Qilu; Honoraria (self ): Sanofi; Honoraria (self ): Merck Sharp & Dohme; Honoraria 96O (self ), Advisory/Consultancy: Innovent Biologics; Honoraria (self ): C-Stone; Honoraria (self ): Luye Pharma; Honoraria (self ), Advisory/Consultancy: Camrelizumab or placebo plus carboplatin and paclitaxel as TopAlliance Biosciences; Honoraria (self ): Amoy Diagnositics. Z. Yang: Full/ first-line treatment for advanced squamous NSCLC (CameL- Part-time employment: Jiangsu Hengrui Medicine. L. Wang: Full/Part-time sq): A randomized, double-blind, multicenter, phase III trial employment: Jiangsu Hengrui Medicine. All other authors have declared no conflicts of interest. C. Zhou1,S.Ren1, J. Chen2,X.Xu3, Y. Cheng4, G. Chen5,Y.Pan6, Y. Fang7, Q. Wang8, Y. Huang9,W.Yao10, R. Wang11,X.Li12, W. Zhang13, Y. Zhang14,S.Hu15, R. Guo16, Z. Yang17, L. Wang17 97O 1Shanghai Pulmonary Hospital, Tongji University, Shanghai, China; First-line pembrolizumab plus chemotherapy for patients 2Hunan Cancer Hospital, Changsha, China; 3Northern Jiangsu People’s with advanced squamous NSCLC: 3-year follow-up from Hospital, Yangzhou, China; 4Jilin Cancer Hospital, Changchun, China; KEYNOTE-407 5Harbin Medical University Cancer Hospital, Harbin, China; 6Anhui 7 Provincial Hospital, Hefei, China; Sir Run Run Shaw Hospital ZheJiang A.G. Robinson1, D. Vicente2, A. Tafreshi3, H. Soto Parra4, 8 University School of Medicine, Hangzhou, China; Henan Cancer Hospital, J. Mazieres5, I. Cicin6, B. Medgyasszay7, J. Rodrıguez-Cid́ 8, 9 Zhengzhou, China; Yunnan Cancer Hospital & The Third Affiliated I. Okamoto9, S. Lee10, R. Ramlau11, V. Vladimirov12, Y. Cheng13, Hospital of Kunming Medical University & Yunnan Cancer Center, B. Halmos14, C-C. Liu15, P. Schwarzenberger15, B. Piperdi15, 10 Kunming, China; Sichuan Provincial Cancer Hospital, Chengdu, China; L. Paz-Ares16 1Cancer Centre of Southeastern Ontario at Kingston 11 12 Anhui Chest Hospital, Hefei, China; The First Affiliated Hospital of General Hospital, Kingston, ON, Canada; 2Hospital Universitario Virgen 13 Zhengzhou University, Zhengzhou, China; The First Affiliated Hospital of Macarena, Seville, Spain; 3Wollongong Private Hospital and Wollongong 14 Nanchang University, Nanchang, China; Shaanxi Provincial Cancer Oncology, Wollongong, Australia; 4AOU Policlinico Vittorio Emanuele, 15 16 Hospital, Xian, China; Hubei Cancer Hospital, Wuhan, China; Jiangsu Catania, Italy; 5Hôpital Larrey, Centre Hospitalier Universitaire Toulouse, 17 Province Hospital, Nanjing, China; Jiangsu Hengrui Medicine Co., Ltd., Toulouse, France; 6Department of Medical Oncology, Trakya University, Shanghai, China Edirne, Turkey; 7Veszpreḿ Megyei Tüdőgyogyinté zet́ Farkasgyepű, ű 8 Background: Cytotoxic agents may potentiate immune-checkpoint Farkasgyep , Hungary; Oncology Center, Medica Sur Hospital, Mexico City, Mexico; 9Kyushu University Hospital, Fukuoka, Japan; 10Department inhibitors with immunological effects. Camrelizumab plus pemetrexed and platinum is a current standard of care for Chinese patients (pts) of Hematology-Oncology, Inje University College of Medicine, Busan, Republic of Korea; 11Poznan University of Medical Sciences, Poznan, with advanced non-squamous NSCLC and negative EGFR/ALK mutation. Poland; 12State Healthcare Institute, Pyatigorsk Oncology Dispensary, Here we evaluated first-line camrelizumab plus chemotherapy (chemo) 13 for pts with squamous NSCLC. Pyatigorsk, Russian Federation; Department of Oncology, Cancer Hospital of Jilin Province, Changchun, China; 14Montefiore Medical Center/ Methods: In this double-blind, multicenter, phase III trial, previously 15 untreated pts with histologically or cytologically confirmed stage IIIB-IV Albert Einstein College of Medicine, Bronx, NY, USA; Merck & Co., Inc., Kenilworth, NJ, USA; 16Department of Medical Oncology, Hospital squamous NSCLC were randomized 1:1 to receive 4–6 cycles of Universitario 12 de Octubre, H12o-CNIO Lung Cancer Unit, Universidad carboplatin (AUC 5) plus paclitaxel (175 mg/m²) with camrelizumab (200 mg) or placebo every 3 weeks, followed by maintenance therapy Complutense & Ciberonc, Madrid, Spain with camrelizumab or placebo. The primary endpoint was PFS per IRC. Background: Pembrolizumab (pembro) + carboplatin and paclitaxel/ Cross-over after disease progression was allowed for pts allocated nab-paclitaxel significantly improved OS and PFS vs placebo in patients placebo plus chemo (pts) with previously untreated stage IV squamous NSCLC in the phase Results: Totally, 389 pts (camrelizumab plus chemo, n = 193; placebo III KEYNOTE-407 study (NCT02775435). At protocol-specified final plus chemo, n = 196) were included. As of Nov. 06, 2020, pts treated with analysis (data cutoff May 9, 2019), HR for OS was 0.71 (95% CI, 0.58– camrelizumab plus chemo were associated with significantly prolonged 0.88). We report long-term data and outcomes for pts who completed 35 IRC-assessed PFS versus placebo plus chemo (median, 8.5 [95% CI 6.9– cycles (∼2 y) of treatment. 10.4] vs 4.9 [95% CI 4.2–5.5] months; HR, 0.37 [95% CI 0.29–0.47], one- Methods: Eligible pts were randomized 1:1 (stratified by paclitaxel vs sided P < 0.0001), with benefit observed in pts with both PD-L1 TPS nab-paclitaxel; East Asia vs rest of the world; and PD-L1 TPS ≥1% vs <1% (HR, 0.49 [95% CI 0.35–0.68]) and ≥1% (HR, 0.34 [95% CI 0.24– <1%) to receive pembro 200 mg + chemo or placebo + chemo Q3W for 4 0.49]). There was also significant improvement in OS for the cycles, then pembro or placebo for up to a total of 35 cycles. Primary camrelizumab plus chemo group (median, NR [18.4–NR] vs 14.5 [95% endpoints were OS and PFS per RECIST v1.1 by blinded independent CI 13.2–16.6] months; HR, 0.55 [95% CI 0.40–0.75], one-sided P < central review. 0.0001). Consistently, confirmed ORR (64.8% [95% CI 57.6%–71.5%] vs Results: 278 pts were randomized to pembro + chemo and 281 to the 36.7% [95% CI 30.0%–43.9%], P < 0.0001) and DoR (median, 13.1 placebo + chemo group. As of Sep 30, 2020, median time from [95% CI 9.3–15.7] vs 4.4 [95% CI 4.2–4.9] months) per IRC favored the randomization to data cutoff was 40.1 (range, 33.1–49.4) mo; 117 camrelizumab plus chemo group. Grade ≥3 treatment-related adverse (41.6%) pts crossed over from the placebo + chemo group to receive events occurred in 73.6% of pts in the camrelizumab plus chemo group pembro monotherapy. Median OS in the pembro + chemo group was and 71.9% in the placebo plus chemo group, with no unexpected adverse 17.2 vs 11.6 mo for placebo + chemo; HR 0.71 (95% CI, 0.59–0.86). 3- effects. year OS rate was 29.7% vs 18.2%, respectively. Median PFS2 was 13.8 vs Conclusions: The addition of camrelizumab to chemotherapy signifi- 9.1 mo, respectively; HR 0.59 (95% CI, 0.49–0.71; Table). Grade 3–5 AEs cantly prolonged PFS and OS in the first-line setting with an acceptable occurred in 74.8% of pts in the pembro + chemo group and 70.0% in the safety profile, supporting this combination as an additional first-line placebo + chemo group. Among 55 pts who completed 35 cycles of treatment option for pts with advanced squamous NSCLC. pembro, ORR was 92.7% (5 CR, 46 PR) and 4 pts (7.3%) had SD. 51 pts Clinical trial identification: NCT03668496. (92.7%) were alive, and 1-year OS and PFS after completion of 35 cycles Legal entity responsible for the study: Jiangsu Hengrui Medicine were 96.0% and 82.6%. 7 pts had initiated a second course of pembro at Co., Ltd. data cutoff. Funding: Jiangsu Hengrui Medicine Co., Ltd.

Journal of Thoracic Oncology Vol. 16 No. 4S: S748–S802 April 2021 Abstracts S749

grant/Funding (institution): Parexel; Research grant/Funding (institution): Taiho. Table 97O: Efficacy outcomes in the ITT population B. Medgyasszay: Honoraria (self ), Research grant/Funding (institution): Merck; Honoraria (self ), Research grant/Funding (institution): BMS; Honoraria (self ), Pembro + Chemo Placebo + Chemo Research grant/Funding (institution): AstraZeneca; Honoraria (self ), Research (n = 278) (n = 281) grant/Funding (institution): Eli Lilly; Honoraria (self ), Research grant/Funding Median OS, mo (95% CI) 17.2 (14.4–19.7) 11.6 (10.1–13.7) (institution): Novartis; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding OS HR (95% CI) 0.71 (0.59–0.86) – – (institution): Eli Lilly; Research grant/Funding (institution): MSD; Research 3-y OS rate, % (95% CI) 29.7 (24.5 35.2) 18.2 (13.8 23.0) grant/Funding (institution): Parexel; Research grant/Funding (institution): – – Median PFS, mo (95% CI) 8.0 (6.3 8.5) 5.1 (4.3 6.0) Quintiles; Research grant/Funding (institution): Taiho. J. Rodrıguez-Cid:́ PFS HR (95% CI) 0.59 (0.49–0.71) Research grant/Funding (institution): MSD; Research grant/Funding (institution): 3-y PFS rate, % (95% CI) 16.1 (12.0–20.8) 6.5 (3.9–10.0) Bayer; Research grant/Funding (institution): BMS; Research grant/Funding Median PFS2,a mo (95% CI) 13.8 (12.2–15.9) 9.1 (8.0–10.3) (institution): Celgene; Research grant/Funding (institution): Eli Lilly; Research PFS2 HR (95% CI) 0.59 (0.49–0.71) grant/Funding (institution): MSD; Research grant/Funding (institution): Roche; ORR, % (95% CI) 62.6 (56.6–68.3) 38.8 (33.1–44.8) Research grant/Funding (institution): Novartis. I. Okamoto: Honoraria (self ), Research grant/Funding (self ): AstraZeneca; Honoraria (self ), Research grant/ Median DOR, mo (range) 9.0 (1.3+ to 45.0+) 4.9 (1.3+ to 44.8+) Funding (self ): BMS; Honoraria (self ), Research grant/Funding (self ): Boehringer +, indicates no PD at last disease assessment. aTime from randomization to Ingelheim; Honoraria (self ), Research grant/Funding (self ): Chugai Pharma; second/subsequent PD on next-line treatment/death. Honoraria (self ), Research grant/Funding (self ): Eli Lilly; Honoraria (self ), Research grant/Funding (self ): MSD Oncology; Honoraria (self ), Research grant/ Funding (self ): Ono Pharmaceutical; Honoraria (self ), Research grant/Funding Conclusions: With ∼3 y of follow-up, pembro + chemo continued to (self ): Taiho; Honoraria (self ): Pfizer; Research grant/Funding (self ): AbbVie; demonstrate durable benefit vs chemo alone without additional toxicity. Research grant/Funding (self ): Astellas Pharma; Research grant/Funding (self ): Novartis. S. Lee: Research grant/Funding (institution), received funding to their Most pts who completed 35 cycles had objective responses and were institutions from Merck to support study conduct: Merck. R. Ramlau: Honoraria alive at data cutoff. These data continue to support pembro + chemo as (self ), received honoraria to self/spouse for scientific advice or as a speaker: first-line treatment in pts with metastatic squamous NSCLC. Amgen; Honoraria (self ), Leadership role, received honoraria to self/spouse for Clinical trial identification: NCT02775435. scientific advice or as a speaker: AstraZeneca; Honoraria (self ), Leadership role, received honoraria to self/spouse for scientific advice or as a speaker: BMS; Editorial acknowledgement: Writing support was provided by Honoraria (self ), Leadership role, received honoraria to self/spouse for scientific Kathleen Estes, PhD, of ICON plc (North Wales, PA, USA), funded by advice or as a speaker: Boehringer Ingelheim; Honoraria (self ), Leadership role, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., received honoraria to self/spouse for scientific advice or as a speaker: Eli Lilly; Kenilworth, NJ, USA. Honoraria (self ), received honoraria to self/spouse for scientific advice or as a speaker: Merck; Honoraria (self ), Leadership role, received honoraria to self/ Legal entity responsible for the study: Merck Sharp & Dohme Corp., a spouse for scientific advice or as a speaker: MSD; Honoraria (self ), Leadership role, subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. received honoraria to self/spouse for scientific advice or as a speaker: Novartis; Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Honoraria (self ), Leadership role, received honoraria to self/spouse for scientific Kenilworth, NJ, USA. advice or as a speaker: Pfizer; Honoraria (self ), Leadership role, received honoraria to self/spouse for scientific advice or as a speaker: Roche; Honoraria Disclosure: A.G. Robinson: Research grant/Funding (institution): AstraZeneca; (self ), received honoraria to self/spouse for scientific advice or as a speaker: Research grant/Funding (institution): Merck; Advisory/Consultancy, Research Sanofi; Leadership role, Board member: AbbVie; Leadership role, Board member: grant/Funding (institution): Pfizer; Research grant/Funding (institution): Roche. Takeda. V. Vladimirov: Research grant/Funding (institution), received funding to D. Vicente: Honoraria (self ), honoraria to self/spouse for scientific advice or as a their institutions from Merck to support study conduct: Merck. Y. Cheng: Research speaker: AstraZeneca; Honoraria (self ), honoraria to self/spouse for scientific grant/Funding (institution), received funding to their institutions from Merck to advice or as a speaker: BMS; Honoraria (self ), honoraria to self/spouse for support study conduct: Merck. B. Halmos: Research grant/Funding (institution): scientific advice or as a speaker: Boehringer Ingelheim; Honoraria (self ), AbbVie; Advisory/Consultancy, Research grant/Funding (institution): honoraria to self/spouse for scientific advice or as a speaker: MSD; Honoraria AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): BMS; (self ), honoraria to self/spouse for scientific advice or as a speaker: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Honoraria (self ), honoraria to self/spouse for scientific advice or as a speaker: Ingelheim; Research grant/Funding (institution): Eli Lilly; Research grant/ Roche. A. Tafreshi: Research grant/Funding (institution), received funding to their Funding (institution): GSK; Advisory/Consultancy, Research grant/Funding institutions from Merck to support study conduct: Merck. H. Soto Parra: Advisory/ (institution): Guardant Health; Advisory/Consultancy, Research grant/Funding Consultancy: AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: (institution): Merck; Research grant/Funding (institution): Mirati; Advisory/ Eli Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy: Roche. J. Mazieres: Consultancy, Research grant/Funding (institution): Novartis; Advisory/ Honoraria (self ), Research grant/Funding (institution): AstraZeneca; Honoraria Consultancy, Research grant/Funding (institution): Pfizer; Research grant/ (self ): Bayer; Honoraria (self ): Blueprint; Honoraria (self ), Research grant/ Funding (institution): Takeda; Advisory/Consultancy: Genentech; Advisory/ Funding (institution): BMS; Honoraria (self ): Boehringer Ingelheim; Honoraria Consultancy: Genentech. C-C. Liu: Full/Part-time employment: Merck Sharp & (self ): Merck; Honoraria (self ), Research grant/Funding (institution): MSD; Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Honoraria (self ): Pfizer; Honoraria (self ): PharmaMar; Honoraria (self ): Pierre P. Schwarzenberger: Full/Part-time employment: Merck Sharp & Dohme Corp., a Fabre; Honoraria (self ), Research grant/Funding (institution): Roche. I. Cicin: subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. B. Piperdi: Full/Part-time Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Advisory/Consultancy, Research grant/Funding (institution): Boehringer Kenilworth, NJ, USA. L. Paz-Ares: Honoraria (self ): Amgen, AstraZeneca, Bayer, Ingelheim; Advisory/Consultancy, Research grant/Funding (institution), Travel/ Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Accommodation/Expenses: Eli Lilly; Advisory/Consultancy: F. Hoffmann-La Lilly, Ipsen, Merck, Merck Sharp and Dohme, Mirati, Novartis, Pfizer, Pharmamar, Roche; Advisory/Consultancy, Research grant/Funding (institution), Travel/ Roche, Sanofi, Servier, Sysmex, Takeda; Speaker Bureau/Expert testimony: Roche, Accommodation/Expenses: MSD; Advisory/Consultancy, Research grant/ Lilly, AstraZeneca, MSD, BMS; Leadership role: Altum Sequencing; Research grant/ Funding (institution), Travel/Accommodation/Expenses: Pfizer; Travel/ Funding (self ): AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme; Accommodation/Expenses: Novartis; Research grant/Funding (institution), Officer/Board of Directors: Genomica;́ Spouse/Financial dependant: AAA, Advanz Travel/Accommodation/Expenses: Quintiles; Travel/Accommodation/Expenses: Pharma, Bayer, HMP, Ipsen, Merck, Midatech Pharma, MSD, Novartis, PharmaMar, Roche; Research grant/Funding (institution): Astellas; Research grant/Funding Pfizer, Pierre Fabre, Roche, Servier and Sanofi. (institution): BMS; Research grant/Funding (institution): Merck Serono; Research S750 Journal of Thoracic Oncology Vol. 16 No. 4S

characteristics were generally well balanced between all randomized, 98O TMB-evaluable and non-evaluable, as well as TMB-high and TMB-low First-line nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles subgroups (both bTMB and tTMB). Overall, clinical benefit (OS, PFS, chemotherapy (chemo) vs 4 cycles chemo in advanced non- ORR) was observed with NIVO + IPI + chemo vs chemo in both TMB- small cell lung cancer (aNSCLC): Association of blood and high and TMB-low subgroups (Table). The OS benefit with NIVO + IPI + chemo vs chemo was similar between tTMB ≥10 and <10 mut/Mb, and tissue tumor mutational burden (TMB) with efficacy in between bTMB ≥16 and <16 mut/Mb subgroups; a numerically higher CheckMate 9LA OS benefit was seen in bTMB ≥20 vs <20 mut/Mb subgroups. For PFS

1 2 3 4 5 and ORR, the magnitude of benefit was higher in TMB-high versus TMB- L. Paz-Ares , T-E. Ciuleanu , M. Cobo , M. Schenker , B. Zurawski , low subgroups for both tTMB and bTMB. J. Menezes6, E. Richardet7, J. Bennouna8, E. Felip9, O. Juan-Vidal10, 11 12 13 14 15 Conclusions: Higher TMB appeared to be associated with improved PFS A. Alexandru , H. Sakai , A. Scherpereel , M. Reck ,S.Lu , and ORR benefits of NIVO + IPI + chemo over chemo. OS benefit was T. John16, S. Meadows-Shropshire17, D. Balli17, S. Agrawal17, 18 1 generally similar between high and low TMB. D.P. Carbone Hospital Universitario 12 de Octubre, CNIO-H12o Lung Clinical trial identification: NCT03215706. Cancer Unit, Universidad Complutense & CiberOnc, Madrid, Spain; 2 Editorial acknowledgement: Writing and editorial assistance were Institutul Oncologic Prof. Dr. Ion Chiricuta and UMF Iuliu Hatieganu, provided by Nick Patterson, of Caudex, London, UK, funded by Bristol 3 ́ ı́ Cluj-Napoca, Romania; Unidad de GestionClnica Intercentros de Myers Squibb. OncologıaMé dica,́ Hospitales Universitarios Regional y Virgen de la 4 Legal entity responsible for the study: Bristol Myers Squibb. Victoria, IBIMA, Malaga, Spain; SF. Nectarie Oncology Center, Craiova, Funding: Bristol Myers Squibb. Romania; 5Ambulatorium Chemioterapii, Bydgoszcz, Poland; 6Hospital 7 Disclosure: L. Paz-Ares: Honoraria (self ): Amgen, AstraZeneca, Bayer, Blueprint Nossa Senhora Da Conceição, Porto Alegre, Brazil; Instituto Oncologicó Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ipsen, de Cordoba,́ Cordoba,́ Argentina; 8Thoracic Oncology Unit, University Merck, Merck Sharp and Dohme, Mirati, Novartis, Pfizer, Pharmamar, Roche, Sanofi, Hospital of Nantes, Nantes, France; 9Vall d’ Hebron University Hospital, Servier, Sysmex, Takeda; Speaker Bureau/Expert testimony: Roche, Lilly, AstraZeneca, MSD, BMS; Leadership role: Altum sequencing; Research grant/ Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; 10Hospital 11 Funding (self ): AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme; Universitario La Fe, Valencia, Spain; Institute of Oncology “Prof. Dr. Officer/Board of Directors: Genomica;́ Spouse/Financial dependant: AAA, Advanz Alexandru Trestioreanu” Bucha, Bucharest, Romania; 12Saitama Cancer Pharma, Bayer, HMP, Ipsen, Merck, Midatech Pharma, MSD, Novartis, PharmaMar, Center, Saitama, Japan; 13Pulmonary and Thoracic Oncology, University of Pfizer, Pierre Fabre, Roche, Servier and Sanofi. T-E. Ciuleanu: Advisory/ 14 Consultancy, Travel/Accommodation/Expenses: AstraZeneca, Amgen, Astellas, Lille, CHU Lille, INSERM U1189, OncoThAI, Lille, France; Department of Boehringer Ingelheim, Bristol-Myers Squibb, Ipsen, Janssen, MSD, Novartis/GSK, Thoracic Oncology, Airway Research Center North, German Center for Pfizer, Roche, Sanofi, Servier. M. Schenker: Research grant/Funding (self ), Fees for Lung Research, LungClinic, Grosshansdorf, Germany; 15Shanghai Lung clinical trial activities : Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Cancer Center, Shanghai Chest Hospital, Shanghai JiaoTong University, Eli Lilly, Gilead, GlaxoSmithKline, Merck, MSD, Mylan, Novartis, Pfizer, Pharma Mar, Regeneron, Roche, Serono. B. Zurawski: Research grant/Funding (self ): Amgen, Shanghai, China; 16Austin Hospital, Heidelberg, Australia; 17Bristol Myers 18 AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Janssen-Cilag, MSD, Roche. Squibb, Princeton, NJ, USA; The Ohio State University Comprehensive J. Bennouna: Honoraria (self ), Advisory/Consultancy: Bristol Myers Squibb, Cancer Center, Columbus, OH, USA Boehringer Ingelheim, AstraZeneca, MSD, Servier, Bayer, Roche; Research grant/ Funding (self ): AstraZeneca; Travel/Accommodation/Expenses: AstraZeneca, Background: In CheckMate 9LA (NCT03215706), 1L NIVO + IPI + Roche. E. Felip: Advisory/Consultancy: AbbVie, Amgen, AstraZeneca, Bayer, chemo (2 cycles) significantly improved overall survival (OS) vs chemo Blueprint Mediines, Boehringer-Ingelheim, Bristol Myers Squibb, Eli Lilly, GSK, Janssen, Merck, MSD, Novartis, Pfizer, Puma Biotechnology, Roche, Sanofi (4 cycles) in patients (pts) with aNSCLC regardless of tumor histology or Genzyme, Takeda; Speaker Bureau/Expert testimony: AstraZeneca, Boehringer- PD-L1 expression. TMB is potentially associated with the clinical efficacy Ingelheim, Bristol Myers Squibb, Eli Lilly, Medscape, MSD, Novartis, Peervoice, of immune checkpoint inhibitors. We evaluated efficacy by tissue and Pfizer, Prime Oncology, Roche, Springer, Takeda, Touchime, CME OUtfitters; blood TMB (tTMB/bTMB) in CheckMate 9LA. Research grant/Funding (self ): Fundacion Merck Salud; Officer/Board of TM Directors: Orifols. O. Juan-Vidal: Advisory/Consultancy: Boehringer Ingelheim, Methods: tTMB was evaluated using the FoundationOne CDx assay Bristol Myers Squibb, Merck Sharp and Dohme, Roche/Genentech, AstraZeneca, from tissue samples collected prior to enrollment. Plasma samples AbbVie, Pfizer, Takeda and Eli Lilly; Speaker Bureau/Expert testimony: Boehringer collected at baseline were used for isolation of circulating cell-free tumor Ingelheim, Bristol Myers Squibb, Merck Sharp and Dohme, Roche/Genentech, DNA and evaluation of bTMB using the Guardant OMNI platform. TMB AstraZeneca; Travel/Accommodation/Expenses: Roche and Merck Sharp and Dohme. A. Alexandru: Advisory/Consultancy: Roche, Boehringer Ingelheim; was not a stratification factor for randomization. Analyses of OS, Speaker Bureau/Expert testimony: Sandoz, Novartis, Bristol Myers Squibb; progression-free survival (PFS), and objective response rate (ORR) were Travel/Accommodation/Expenses: Boehringer Ingelheim, Sanofi, Pfizer, Roche, based on prespecified TMB thresholds (tTMB, 10 mut/Mb; bTMB, 16 AstraZeneca, Bristol Myers Squibb. H. Sakai: Advisory/Consultancy: Bristol Myers and 20 mut/Mb). Analyses were based on the March 9, 2020 database Squibb, Merck KGaA; Speaker Bureau/Expert testimony: Bristol Myers Squibb, Ono Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Merck & Co, Merck lock (DBL; minimum OS follow-up, 12.7 mo). KGaA. A. Scherpereel: Advisory/Consultancy: AstraZeneca, Bristol Myers Squibb, Results: Of 711 randomized pts with available TMB data at DBL, 64% MSD, Roche; Speaker Bureau/Expert testimony: AstraZeneca, Bristol Myers had evaluable tTMB and 73% had evaluable bTMB. Baseline Squibb, MSD; Research grant/Funding (institution): Bristol Myers Squibb;

Table 98O: Efficacy outcomes in subgroups based on blood and tissue TMB

TMB cut-off (mut/Mb)

tTMB ≥10 tTMB <10 bTMB ≥16 bTMB <16 bTMB ≥20 bTMB <20

N+I+ N+I+ N+I+ N+I+ N+I+ chemo chemo Chemo chemo chemo Chemo N+I+ chemo Chemo n= Chemo n= n= n= Chemo n= n= chemo Chemo n= n= 101 n=82 135 138 113 n=85 165 156 n=80 n=61 196 180 Median OS, mo 15.0 10.8 16.8 12.4 15.4 10.4 15.0 11.2 19.4 11.4 14.1 10.8 HR (95% CI) 0.74 (0.51–1.08) 0.75 (0.55–1.02) 0.60 (0.42–0.86) 0.73 (0.55–0.96) 0.54 (0.35–0.84) 0.74 (0.57–0.95) Median PFS, mo 8.9 4.7 5.6 5.0 7.2 5.3 5.6 4.5 9.7 5.3 5.6 4.5 HR (95% CI) 0.49 (0.34–0.70) 0.83 (0.63–1.10) 0.55 (0.39–0.78) 0.78 (0.60–1.00) 0.48 (0.32–0.73) 0.78 (0.62–0.99) ORR, % 46 28 33 27 49 27 33 28 55 31 33 27 April 2021 Abstracts S751

Travel/Accommodation/Expenses: AstraZeneca, Bristol Myers Squibb, MSD, Methods: KRYSTAL-1 (NCT03785249) is a multi-cohort phase I/II Roche. M. Reck: Advisory/Consultancy: AbbVie, Amgen, AstraZeneca, Bristol study evaluating adagrasib in pts with advanced or metastatic solid Myers Squibb, Boehringer-Ingelheim, Lilly, Merck, MSD, Novartis, Pfizer, Roche, G12C Samsung; Speaker Bureau/Expert testimony: AstraZeneca, Bristol Myers Squibb, tumors, including NSCLC, harboring a KRAS mutation previously Boehringer-Ingelheim, Lilly, Merck, MSD, Novartis, Pfizer, Roche; Research grant/ treated with chemotherapy and an anti-PD-(L)1. Exploratory endpoints Funding (self ): Bristol Myers Squibb, Boehringer-Ingelheim; Travel/ include correlative analysis of co-occurring genetic alterations in tumor Accommodation/Expenses: AbbVie, Amgen, AstraZeneca, BMS, Boehringer- tissue at baseline and evaluation of the modulation of PD markers, Ingelheim, Lilly, Merck, MSD, Novartis, Pfizer, Roche. S. Lu: Advisory/ Consultancy: AstraZeneca, Boehringer-Ingelheim, Hutchison MediPharma, including transcriptomics, in pretreatment and on-study biopsies. Simcere, ZaiLab, GenomiCare and Roche; Speaker Bureau/Expert testimony: Results: As of 30 August 2020, 79 pts with pretreated NSCLC were AstraZeneca, Roche, Hansoh. T. John: Honoraria (self ): Bristol Myers Squibb, treated with adagrasib 600 mg BID (phase I/Ib and phase II). Most AstraZeneca, Roche, Merck, MSD, Boehringer Ingelheim, Bayer; Honoraria commonly reported (>20%) TRAEs included: nausea (54%), diarrhea (institution): Specialised Therapeutics, Pfizer, Novartis; Advisory/Consultancy: MSD, Merck, Roche, AstraZeneca, Bristol Myers Squibb, Takeda, BI, Bayer. (48%), vomiting (34%), fatigue (28%), and increased ALT (23%). S. Meadows-Shropshire: Research grant/Funding (self ), Travel/Accommodation/ Among the 51 pts evaluable for clinical activity, 45% (23/51) had a Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: partial response (PR) and 26 pts had stable disease (SD). In a Bristol Myers Squibb. D. Balli: Shareholder/Stockholder/Stock options, Full/Part- subpopulation of pts with STK11-comutations, ORR was 64% (9/14). time employment: Bristol Myers Squibb. S. Agrawal: Full/Part-time employment: Bristol Myers Squibb. D.P. Carbone: Honoraria (self ): AstraZeneca, Pfizer, Bristol Preliminary PD and mechanistic biomarker analyses on pre- and post- Myers Squibb, Eisai; Advisory/Consultancy: AstraZeneca, EMD Serono/Merck, GI treatment tumor NSCLC biopsies (n = 3) demonstrate downregulation of Therapeutics (Intellisphere), Gritstone Oncology, GSK, Inivata, Roche China, KRAS/MAPK pathway genes including DUSP6 and SPRY4. In pts with Oncocyte, GenePlus, Gloria Biosciences, Roche, BMS, Daiichi Sankyo Inc, tumors harboring STK11-comutations, there was minimal expression of Boehringer-Ingelheim, Seattle Genetics, Flame Biosciences, Novocure; Leadership role, Chair of the Lung Biology subcommittee for the Eastern immune transcripts (eg, CD4 and CD8) at baseline and these transcripts Cooperative Oncology Group and on the Thoracic Core committees for both the were increased after treatment with adagrasib suggesting a potential Alliance and ECOG/ACRIN. I am also Past-President of the International immune response to therapy. Association for the Study of Lung Cancer (IASLC).: ECOG, ECOG/ACRIN, IASLC; Conclusions: Adagrasib is tolerable and has demonstrated clinical Research grant/Funding (institution): Bristol Myers Squibb; Travel/ G12C Accommodation/Expenses: AbbVie, AstraZeneca, Bristol Myers Squibb, EMD activity in pts with previously treated KRAS -mutant NSCLC. Serono, Inivata, Inovio, Janssen, Loxo Oncology, Merck, MSD, Pfizer, Roche/ Additional PD and mechanistic data will be presented. Genentech, Takeda Oncology, Trinity, Incyte, Kyowa Kirin, Novartis, Gritstone Clinical trial identification: NCT03785249. Oncology, GSK, Roche China GenePlus, Daiichi Sankyo Inc; Officer/Board of Editorial acknowledgement: Editorial support was provided by Robin Directors: IASLC, LCFA, LUNGevity, ALCMI, Joan’s Legacy Foundation, Lance Armstrong Foundation, Wendy Wyrick Foundation, Wendy Will Case Foundation, Serody of Axiom Healthcare Strategies. Jack Roth Foundation. All other authors have declared no conflicts of interest. Legal entity responsible for the study: Mirati Therapeutics, Inc. Funding: Mirati Therapeutics, Inc. Disclosure: G.J. Riely: Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda; Advisory/Consultancy: Mirati 99O_PR Therapeutics. S-H.I. Ou: Advisory/Consultancy: Pfizer; Advisory/Consultancy: KRYSTAL-1: Activity and preliminary pharmacodynamic (PD) Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Takeda; Advisory/Consultancy: TP Therapeutics; Speaker Bureau/Expert testimony: analysis of adagrasib (MRTX849) in patients (Pts) with Genentech; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/ advanced non–small cell lung cancer (NSCLC) harboring Expert testimony: Takeda; Shareholder/Stockholder/Stock options: Turning Point KRASG12C mutation Therapeutics. I. Rybkin: Advisory/Consultancy: AstraZeneca. A. Spira: Shareholder/Stockholder/Stock options: Lilly; Advisory/Consultancy: Incyte; Advisory/Consultancy: Amgen; Advisory/Consultancy: Novartis; Advisory/ 1 2 3 4 5 G.J. Riely , S-H.I. Ou , I. Rybkin , A. Spira , K. Papadopoulos , Consultancy: Mirati Therapeutics, Inc; Advisory/Consultancy: Gritstone; J.K. Sabari6, M. Johnson7, R.S. Heist8, L. Bazhenova9, M. Barve10, Advisory/Consultancy: Jazz Pharmaceuticals; Honoraria (self ): CytomX J.M. Pacheco11, K. Velastegui12, C. Cilliers12, P. Olson12, Therapeutics; Honoraria (self ): AstraZeneca/MedImmune; Honoraria (self ): 12 12 12 ̈ 13 1 Merck; Honoraria (self ): Takeda; Honoraria (self ): Amgen; Honoraria (self ): J.G. Christensen , T. Kheoh , R.C. Chao , P.A. Janne Thoracic Janssen Oncology; Honoraria (self ): Novartis; Honoraria (self ): Bristol Myers Oncology Service, Division of Solid Tumor, Department of Medicine, Squibb; Honoraria (self ): Bayer. K. Papadopoulos: Advisory/Consultancy: Bayer; Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, Advisory/Consultancy: ArQule; Advisory/Consultancy: Basilea. M. Johnson: New York, NY, USA; 2University of California Irvine, Orange, AL, USA; Spouse/Financial dependant: Otsuka; Travel/Accommodation/Expenses: AbbVie; 3 Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/ Henry Ford Cancer Institute, Henry Ford Hospital, Detroit, MI, USA; Expenses: Genentech; Travel/Accommodation/Expenses: Incyte; Travel/ 4 5 Research Institute, Virginia Cancer Specialist, Fairfax, VA, USA; Clinical Accommodation/Expenses: Merck; Travel/Accommodation/Expenses: Pfizer; Research Department, South Texas Accelerated Research Therapeutics Travel/Accommodation/Expenses: Sanofi. R.S. Heist: Advisory/Consultancy: (START), San Antonio, TX, USA; 6Perlmutter Cancer Center, New York Boehringer Ingelheim; Advisory/Consultancy: Novartis; Advisory/Consultancy: 7 Tarveda; Advisory/Consultancy: Apollonia; Honoraria (self ): Chugai/Roche. University Langone Health, New York, NY, USA; Lung Cancer Research, L. Bazhenova: Shareholder/Stockholder/Stock options: Epic Sciences; Advisory/ Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN, USA; Consultancy, Research grant/Funding (self ): Beyond Spring Pharmaceuticals; 8Massachusetts General Hospital, Boston, MA, USA; 9Medicine, Moores Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Takeda; Advisory/ Cancer Center - UC San Diego Health, La Jolla, CA, USA; 10Mary Crowley Consultancy: Roche; Advisory/Consultancy: Blueprint Medicines; Advisory/ 11 Consultancy: G1; Advisory/Consultancy: Bayer; Advisory/Consultancy: Cancer Research, Dallas, TX, USA; Division of Medical Oncology, Boehringer Ingelheim; Advisory/Consultancy: Novartis; Advisory/Consultancy: Department of Medicine, University of Colorado Anschutz Medical Regeneron; Advisory/Consultancy: Merck; Advisory/Consultancy: Johnson & Campus, Aurora, CO, USA; 12Mirati Therapeutics, Inc., San Diego, CA, USA; Johnson; Advisory/Consultancy: BMSi; Advisory/Consultancy: Daichi Sankyo; 13Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Advisory/Consultancy: Neuvogen. J.M. Pacheco: Advisory/Consultancy, Travel/ Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/ Boston, MA, USA Accommodation/Expenses: Novartis; Advisory/Consultancy: Hengrui; Advisory/ Consultancy: Gerson Lehrman; Advisory/Consultancy, Travel/Accommodation/ Background: KRAS, the most frequently mutated oncogene in cancer, is Expenses: Pfizer; Honoraria (self ), Travel/Accommodation/Expenses: Takeda. a key mediator of the RAS/MAPK signaling cascade that promotes K. Velastegui: Full/Part-time employment: Mirati Therapeutics, Inc. C. Cilliers: cellular growth and proliferation. KRASG12C mutations occur in Full/Part-time employment: Mirati Therapeutics, Inc. P. Olson: Full/Part-time approximately 14% of NSCLC (adenocarcinoma). Adagrasib, an inves- employment: Mirati Therapeutics, Inc. J.G. Christensen: Leadership role, G12C Shareholder/Stockholder/Stock options, Officer/Board of Directors: Mirati tigational agent, is a potent, covalent inhibitor of KRAS that Therapeutics, Inc; Advisory/Consultancy: BridgeBio; Leadership role, G12C irreversibly and selectively binds to KRAS , locking it in its inactive Shareholder/Stockholder/Stock options: BCTG Acquisition; Shareholder/ state and was optimized for favorable PK properties, including oral Stockholder/Stock options: Bluebird Bio. T. Kheoh: Shareholder/Stockholder/ bioavailability, long half-life (∼24 h), and extensive tissue distribution. Stock options, Full/Part-time employment: Mirati Therapeutics, Inc; Shareholder/ Stockholder/Stock options: Tocagen. R.C. Chao: Shareholder/Stockholder/Stock options, Full/Part-time employment: Mirati Therapeutics, Inc. P.A. Janne:̈ S752 Journal of Thoracic Oncology Vol. 16 No. 4S

Shareholder/Stockholder/Stock options: Gatekeeper Pharmaceuticals; Advisory/ (14/11 and 8/4 in O and P arms, respectively). Median PFS was 2.3 and Consultancy, Shareholder/Stockholder/Stock options: Loxo; Research grant/ 2.1 months in the O and P arms, respectively (HR = 0.89, IC 95% 0.51– Funding (self ): Revolution Medicines; Advisory/Consultancy, Research grant/ Funding (self ): Takeda; Research grant/Funding (self ): Puma Biotechnology; 1.55; p = 0.68); median OS was 9.5 and 14.1 months in the O and P arms, Advisory/Consultancy, Research grant/Funding (self ): Boehringer Ingelheim; respectively (HR = 1.29 IC 95% 0.68–2.45; p = 0.44). Grade ≥3 adverse Advisory/Consultancy, Research grant/Funding (self ): Lilly; Advisory/ events (AEs) occurred in 14 and 4 pts in O and P arms; 10 AEs (8 in the O Consultancy, Research grant/Funding (self ): Daichi Sankyo; Research grant/ arm) led to treatment discontinuation; 38 pts (23 in O and 15 in P arms) Funding (self ): Astellas; Advisory/Consultancy, Research grant/Funding (self ): AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Merrimack; received second-line systemic therapy, including immunotherapy in 12 Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Chugai; and 9 pts in the O and P arms, respectively. Advisory/Consultancy: Mirati Therapeutics, Inc; Advisory/Consultancy: Araxes; Conclusions: PIPSeN was terminated early with only 50% of the pre- Advisory/Consultancy: Ignyta; Advisory/Consultancy: Novartis; Advisory/ planned pts population available for analysis, thus being statistically Consultancy: Biocartis; Advisory/Consultancy: Voronoi; Advisory/Consultancy: SFJ Pharmaceuticals; Advisory/Consultancy: Silicon Therapeutics. All other underpowered. Although well tolerated, olaparib maintenance did not authors have declared no conflicts of interest. improve median PFS nor median OS in this sample of pts with platinum- sensitive NSCLC. Clinical trial identification: NCT02679963. 100MO Legal entity responsible for the study: Gustave Roussy. Funding: AstraZeneca. Olaparib maintenance vs placebo in platinum-sensitive non- Disclosure: S. Postel-Vinay: Research grant/Funding (institution): Boehringer small cell lung cancer: The phase II randomized PIPSeN trial Ingelheim, Roche, Merck KGaA, AstraZeneca; Research grant/Funding (institution), Principal or co-investigator of clinical trials: AbbVie, Adaptimmune, Aduro S. Postel-Vinay1, D. Planchard2, M. Antigny2, J. Coves Sarto3, Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex 4 5 6 Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, M. Domine Gomez , R. de las Penas Bataller , M.A. Sala Gonzalez , Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Blueprint Medicine. 7 8 2 9 S. Viteri , J. Pozas Pérez , M. Texier , A.L. Ortega Granados , D. Planchard: Advisory/Consultancy: AstraZeneca, Bristol-Myers Squibb, M.T. Moran Bueno10, C.J. Camps11, A. Lopez-Martin12, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, M. Provencio13, A. Gazzah2, J-C. Soria14, B. Besse15, prIME Oncology, Peer CME, Roche, Samsung; Honoraria (self ): AstraZeneca, 16 17 1 Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, B. Massuti Sureda , R. Rosell Drug Development Department, Pfizer, prIME Oncology, Peer CME, Roche, Samsung; Travel/Accommodation/ 2 Institut Gustave Roussy, Villejuif, France; Institut Gustave Roussy, Villejuif, Expenses: AstraZeneca, Roche, Novartis, prIME Oncology, Pfizer; Research grant/ France, 3Hospital Son Llatzer, Palma De Mallorca, Islas Baleares, Spain; Funding (institution), Principal or co-investigator of clinical trials: AstraZeneca, 4University Hospital “Fundacion Jimenez Diaz”, Madrid, Spain; 5Medical Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, ́ 6 Roche, MedImmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo. Oncology, Hospital Provincial Castellon, Castellon, Spain; Hospital de A. Gazzah: Research grant/Funding (institution), Principal or co-investigator of 7 Basurto, Bilbao, Spain; Instituto Oncologicó Dr Rosell, Hospital clinical trials: AbbVie, Adaptimmune, Aduro Biotech, Agios Pharmaceuticals, Universitari Dexeus, Grupo QuironSalud, Barcelona, Spain; 8Dept. Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca Ab, Oncologia Medica, Hospital Universitario Ramon y Cajal, Madrid, Spain; Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb 9 ́ Technologies Bv, Beigene, Blueprint Medicine. J-C. Soria: Honoraria (self ), Medical Oncology Department, Hospital Universitario de Jaen, Jaen, Advisory/Consultancy: AstraZeneca, Bayer, Blend Therapeutics, Boehringer- 10 Spain; Medical Oncology Dept, ICO - Institut Catalàd’Oncologia Ingelheim, Clovis, Eli Lilly, Gammamabs, Merus, Mission Therapeutics, Pfizer, Badalona (Hospital Universitario Germans Trias i Pujol), Badalona, Pharmamar, Pierre Fabre, Roche, Sanofi, Servier, Symphogen, Tarveda; Barcelona, Spain; 11Hospital General Universitario Valencia, Valencia, Shareholder/Stockholder/Stock options: Gritstone; Full/Part-time employment, 12 13 ́ Sept 2017 to Dec 2019: AstraZeneca. B. Besse: Research grant/Funding Spain; Hospital Severo Ochoa, Madrid, Spain; Universidad Autonoma (institution): AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, de Madrid, Instituto de Investigacioń Puerta de Hierro, Hospital Puerta de Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Cristal Therapeutics, Hierro de Majadahonda, Majadahonda, Spain; 14General Director, Institut Daiichi-Sankyo, Eli Lilly, GSK, Ignyta, IPSEN, Inivata, Janssen, Merck KGaA, MSD, Gustave Roussy, Villejuif, France; 15Cancer Medicine Department, Institut Nektar, Onxeo, OSE immunotherapeutics, P. All other authors have declared no conflicts of interest. Gustave Roussy, Villejuif, France; 16Medical Oncology Department, Hospital General Universitario de Alicante, Alicante, Spain; 17Cancer Biology & Precision Medicine Program Dept, HUGTP - Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain 101MO Efficacy and safety of DCVAC/LuCa with chemotherapy for Background: Non-small cell lung cancer (NSCLC) displays frequent patients with stage IV NSCLC: A prospective, open-label, DNA damage response (DDR) defects. DDR defects leading to platinum single-arm, phase II study sensitivity widely overlap with those underlying Poly (ADP-ribose) polymerase inhibitors (PARPi) sensitivity. PIPSeN (NCT02679963) is a X. Ling, J. Xu, R. Zhong, H. Zhong, B. Han Department of Pulmonary randomized double-blind phase II study that evaluated the PARPi Medicine, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong olaparib as maintenance treatment in patients (pts) with platinum- University, Shanghai, China sensitive advanced NSCLC. Methods: Chemonaïve ECOG PS 0–1 pts with stage IIIB-IV NSCLC with Background: Appropriate treatment for advanced non-small cell lung no EGFR or ALK/ROS alteration were eligible in this Gustave Roussy- cancer (NSCLC) remains a challenging problem. Newly clinically applied sponsored AstraZeneca-funded academic study. Pts with partial or immune checkpoint inhibitors (ICIs) still show a low response rate. complete response after 4–6 cycles of platinum-based chemotherapy Therefore, more effective therapies are still needed. Here, we report the were randomized (R) between olaparib maintenance (O, 300 mg BID) or results of a phase II clinical trial combining DCVAC/LuCa to chemother- placebo (P). Primary objective was progression-free survival (PFS) from apy as treatment for stage IV non-squamous NSCLC. R according to RECIST v1.1. Secondary objectives included overall Methods: Patients with stage IV, non-squamous NSCLC without genetic survival (OS) and safety. R was stratified according to age, histology and variants and had not received systemic therapy for NSCLC prior to country. With an anticipated HR = 0.65, 500 enrolled pts were required treatment, were enrolled in this study. DCVAC/LuCa were manufactured to randomize 144 pts. Because of the registration of anti-PD-L1 agents in after collecting peripheral blood mononuclear cells (PBMC) from the the first-line setting, the trial was closed prematurely. patients. DCVAC/LuCa was applied since the third cycle of chemotherapy. Results: 182 pts were enrolled and 60 pts randomized (33 and 27 in the Primary endpoint for efficacy was overall survival (OS). For safety O and P arms, respectively); median age was 63; 63% had adenocar- analysis, we assessed adverse events (AEs), treatment-related AEs cinoma, 3% were never-smokers. Pts and tumor characteristics were (TRAEs) and AEs of special interest (AESIs). well-balanced between arms, except for bone/peripheral metastasis April 2021 Abstracts S753

Results: Between January 2016 and March 2018, 61 patients were Conclusions: In the IMpower132 China cohort, PFS benefit was seen in enrolled. The OS rate at 2 year in mITT population was 52.57% and the the APP vs PP arm, consistent with the global population. Interim OS median OS was not reached (95% CI, 19.4 to could not be calculated). data, though immature, showed numerical OS benefit in the APP vs PP The median PFS was 8.0 months (95% CI 5.4 to 11.9). ORR was 31.82% arm. The safety profile of APP was consistent with the known risks of the and median TTP was 10.2 months (95% CI 3.6 to 15.7). Patients’ individual treatment components; no new safety signals were identified. prognosis was significantly related to the number of doses of DCVAC. Clinical trial identification: NCT02657434. Eight (13.33%) of the sixty assessed patients had grade 3 or over 3 Editorial acknowledgement: Medical writing assistance for this TRAEs, none of which were related to leukapheresis or DC vaccination. abstract was provided by Derrick Afful, PhD, and Kia Walcott, PhD, of Six grade 1 TRAEs were considered associated with leukapheresis. No Health Interactions. DCVAC-induced AEs were observed. Legal entity responsible for the study: F. Hoffmann-La Roche, Ltd. Conclusions: In stage IV, non-squamous NSCLC without genetic Funding: F. Hoffmann-La Roche, Ltd. variants, the combination therapy of DCVAC/LuCa with pemetrexed Disclosure: S. Lu: Research grant/Funding (institution): AstraZeneca; Research plus carboplatin has a clinical activity and a favorable tolerability profile. grant/Funding (institution): Hutchison; Research grant/Funding (institution): Our results are a foundation for further randomized controlled clinical BMS; Research grant/Funding (institution): Heng Rui Beigene; Research grant/ Funding (institution): Roche; Speaker Bureau/Expert testimony: AstraZeneca; trials of this therapy. Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Clinical trial identification: NCT02669719. Hansoh; Speaker Bureau/Expert testimony: Hengrui Therapeutics; Advisory/ Legal entity responsible for the study: The authors. Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Funding: Shanghai Chest Hospital affiliated to Shanghai Jiaotong Boehringer Ingelheim; Advisory/Consultancy: Hutchison MediPharma; Advisory/ Consultancy: Simcere; Advisory/Consultancy: ZaiLab; Advisory/Consultancy: University. GenomiCare; Advisory/Consultancy: Yuhan Corporation; Advisory/Consultancy: Disclosure: All authors have declared no conflicts of interest. PrIME Oncology; Advisory/Consultancy: Menarini; Advisory/Consultancy: Roche. J. Xia: Full/Part-time employment: Roche (China) Holding Ltd. J. Yi: Full/Part-time employment: Genentech; Shareholder/Stockholder/Stock options: Roche; Spouse/Financial dependant: Genentech. All other authors have declared no 102P conflicts of interest. Primary results from the China cohort of IMpower132: Atezolizumab (atezo) + carboplatin (carbo) or cisplatin (cis) + pemetrexed (pem) as first-line therapy in advanced NSCLC 103P First-line avelumab in combination with cetuximab and 1 2 2 3 4 5 6 7 S. Lu , J. Fang , Z. Wang ,Y.Fan , Y. Liu ,J.He , B. Cao , J. Zhou , chemotherapy in patients with advanced squamous non-small 8 9 9 9 10 11 1 J. Hu ,J.Xia ,W.Liu ,J.Shi ,J.Yi , L. Cao Shanghai Chest Hospital, cell lung cancer (NSCLC) Shanghai, China, 2Beijing Cancer Hospital, Beijing, China, 3Zhejiang 4 Cancer Hospital, Hangzhou, China; First Hospital, China Medical 1 ́ 2 3 4 5 5 Z.G. Andric ,G.Galffy , M. Cobo Dols , B. Szima , G. Stojanovic , University, Shenyang, China; Guangzhou Medical University, First 6 7 8 9 6 M.D. Petrovic , E. Felip Font , D. Vicente Baz , S. Ponce Aix , Hospital, Guangzhou, China; Beijing Friendship Hospital, Capital Medical 10 11 12 13 7 O. Juan-Vidal , S. Tehenes , Z. Szalai , G. Losonczy , University, Beijing, China; Zhejiang University School of Medicine, First 14 15 16 16 8 A. Calles Blanco , R. Bernabe , K. Duecker , D. Zhou , Hospital, Hangzhou, China; Zhongshan, Fudan University, Shanghai, 16 16 17 1 9 10 A. Schroeder , G. Guezel , F. Ciardiello Medical Oncology Dep., China; F. Hoffmann-La Roche Ltd, Shanghai, China; Genentech, Inc, 2 11 Clinical Hospital Center Bezanijska Kosa, Belgrade, Serbia; Pulmonology South San Francisco, CA, USA; Anhui Provincial Hospital, Hefei, China 3 Hospital Törökbalint,́ Törökbalint,́ Hungary; Department of Medical ́ Background: IMpower132 is a phase III study evaluating atezo + pem + Oncology, Hospital Regional Universitario de Malaga, IBIMA, Malaga, 4 5 cis/carbo (APP) in stage IV non-squamous (nsq) EGFR/ALK-negative Spain; Markusovszky Hospital, Szombathely, Hungary; Institute of 6 NSCLC. The coprimary PFS endpoint was met in the ITT population at the Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia; Clinic for 7 primary analysis (HR 0.60; 95% CI 0.49, 0.72; P < 0.0001) Pulmonology, Clinical Center Kragujevac, Kragujevac, Serbia; Vall d’ (Papadimitrakopoulou, WCLC 2018). The coprimary OS endpoint was Hebron University Hospital, Vall d’ Hebron Institute of Oncology, 8 not met at the final analysis, although numerical improvement in mOS was Barcelona, Spain; Department of Medical Oncology, Hospital 9 seen in the APP vs control arm (Nishio, ESMO Asia 2020). Here we report Universitario Virgen Macarena, Seville, Spain; Medical Oncology primary data from the IMpower132 China cohort, including 1 patient (pt) Department, H120-CNIO Lung Cancer Unit, Hospital Universitario 12 de from the global population and 162 pts from the China extension phase. Octubre, Universidad Complutense and Ciberonc, Madrid, Spain; 10 ̀ 11 Methods: In the China cohort, treatment-naive pts with nsq stage IV Hospital Universitari I Politecnic La Fe, Valencia, Spain; St. Raphael EGFR/ALK-negative NSCLC were randomised 1:1 to receive 4 or 6 cycles Hospital of Zala County, Zalaegerszeg, ZalaCounty, Hungary; 12 of cis 75 mg/m2 + pem 500 mg/m2 Q3W alone (PP arm) or with atezo Department of Pulmonology, Aladar Petz University Teaching Hospital, 13 1200 mg Q3W (APP arm) followed by maintenance pem (PP arm) or Győr, Hungary; Semmelweis University I. Faculty of Medicine, Budapest, 14 atezo + pem (APP arm). Coprimary endpoints were investigator- Hungary; Medical Oncology Department, Hospital General Universitario 15 assessed PFS (RECIST 1.1) and OS; key secondary endpoints included Gregorio Marañon, Madrid, Spain; Hospital Universitario Virgen del 16 17 ORR, DOR and safety. Rocio, Seville, Spain; Merck KGaA, Darmstadt, Germany; The Results: A total of 82 (APP) and 81 (PP) pts were enrolled. At data cutoff University of Campania Luigi Vanvitelli, Naples, Italy (18 July 2019), median survival follow-up was 11.7 mo in all 163 pts. Background: Avelumab (anti–PD-L1 mAb) is approved in Merkel cell Baseline characteristics were generally balanced between arms. At the carcinoma, urothelial carcinoma and in combination with axitinib for final PFS analysis, mPFS was 8.3 (APP) vs 5.8 mo (PP; HR 0.73; 95% CI renal cell carcinoma in various countries. Preclinical data suggest 0.5, 1.08). At the interim OS analysis conducted at the time of the final avelumab may have an enhanced treatment effect in combination with PFS analysis, mOS was not estimable in both arms (HR 0.70; 95% CI 0.40, cetuximab (anti–EGFR mAb) and cisplatin, including in NSCLC. We 1.24). In the APP and PP arms, 31% and 40% of pts received subsequent report results of avelumab plus cetuximab and platinum-based non-protocol anticancer therapies, including immunotherapy in 0 (APP) chemotherapy in patients with advanced squamous NSCLC. and 12% (PP). Confirmed ORR was 56% (APP) and 27% (PP); mDOR Methods: This phase IIa study (NCT03717155) enrolled patients with was 6.7 (APP) and 8.5 (PP) mo. Gr 3/4 TRAEs occurred in 62% (APP) previously untreated histologically confirmed, stage IV, recurrent or and 46% (PP) of pts; 2% of pts in each arm had Gr 5 TRAEs. AEs of metastatic, squamous NSCLC without EGFR/ALK mutations. Patients special interest occurred in 74% (APP) and 42% (PP) of pts; these were received avelumab 800 mg (days 1 and 8); cetuximab 250 mg/m2 (day Gr 3/4 in 10% (APP) and 6% (PP). S754 Journal of Thoracic Oncology Vol. 16 No. 4S

1) and 500 mg/m2 (day 8); cisplatin 75 mg/m2 (day 1); and gemcitabine AstraZeneca; Honoraria (self ), Advisory/Consultancy: Pfizer; Honoraria (self ), 1250 mg/m2 (days 1, 8) for 4 × 3-week cycles followed by avelumab Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria 2 (self ), Advisory/Consultancy: Novartis; Honoraria (self ), Advisory/Consultancy, 800 mg and cetuximab 500 mg/m maintenance every 2 weeks until Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self ), progression, unacceptable toxicity, or withdrawal. The primary endpoint Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & was investigator-assessed confirmed best overall response (BOR) per Dohme; Honoraria (self ), Advisory/Consultancy: Takeda; Honoraria (self ), RECIST 1.1. Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim. R. Bernabe: Research grant/Funding (institution): Roche. K. Duecker: Results: 43 patients were enrolled. As of July 2, 2020 (primary analysis), Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck 15 patients (34.9%) remained on study treatment. Confirmed BOR was KgaA, Darmstadt, Germany. D. Zhou: Shareholder/Stockholder/Stock options, partial response (PR) in 13 patients (ORR, 30.2% [95% CI, 17.2%– Full/Part-time employment: Merck KGaA, Darmstadt, Germany. A. Schroeder: 46.1%]; disease control rate, 79.1%). Median duration of confirmed Honoraria (self ), Leadership role, Travel/Accommodation/Expenses, ≥ Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck response was 7.1 months and 60.8% of responses lasted 6 months. KGaA, Darmstadt, Germany; Shareholder/Stockholder/Stock options: Overall, 23 patients had unconfirmed or confirmed PR (ORR, 53.5% GlaxoSmithKline; Shareholder/Stockholder/Stock options: Pfizer; Shareholder/ [95% CI, 37.7%–68.8%]). Treatment-related adverse events (TRAEs) Stockholder/Stock options: BioNTech; Shareholder/Stockholder/Stock options: occurred in 38 patients (88.4%), which were grade ≥3 in 24 (55.8%; Eisai. G. Guezel: Full/Part-time employment: Merck KGaA, Darmstadt, Germany. F. Ciardiello: Advisory/Consultancy, Research grant/Funding (institution): Merck; most common was neutropenia [n = 12; 27.9%]). No treatment-related Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/ deaths occurred. As of Nov 4, 2020 (updated analysis), median Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, progression-free and overall survival were 6.1 and 10.0 months, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Servier; respectively. Updated data, including biomarker data will be presented. Advisory/Consultancy: Symphogen; Research grant/Funding (institution): Pfizer. All other authors have declared no conflicts of interest. Conclusions: The combination of avelumab, cetuximab, cisplatin and gemcitabine showed clinical activity and a manageable safety profile with no additional safety signals for avelumab or cetuximab. Clinical trial identification: NCT03717155. 104P Editorial acknowledgement: Medical writing support was provided by Fast progression in high PD-L1 NSCLC treated with Abhijith Thippeswamy and Mark Holland of ClinicalThinking and was pembrolizumab in first-line: A prognostic scoring system funded by Merck KGaA, Darmstadt, Germany and Pfizer. based on clinical features Legal entity responsible for the study: Merck KGaA, Darmstadt, Germany and Pfizer. A. Passaro1, D. Giannarelli2, E. Bria3, S. Novello4, D. Galetta5, Funding: This study was sponsored by Merck KGaA, Darmstadt, A.J. Gelibter6, M.L. Reale4, S. Carnio4, E. Vita3, A. Stefani3, Germany and is part of an alliance between Merck KGaA and Pfizer. P. Pizzutilo5, V. Stati1, I. Attili1, F. de Marinis1 1Division of Thoracic Disclosure: B. Szima: Research grant/Funding (self ), Principle Investigator: Oncology, European Institute of Oncology, IRCCS, Milan, Italy; 2Istituto IQVIA. E. Felip Font: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Nazionale Tumori Regina Elena, IRCCS, Rome, Italy; 3Comprehensive Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; “ ” Advisory/Consultancy: Bayer; Advisory/Consultancy: Blue Print Medicines; Cancer Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Rome, Italy; 4Oncology Dept., Universitàdegli Studi di Torino - Orbassano, Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol- Orbassano, Italy; 5IRCCS Oncologico Giovanni Paolo II, Bari, Italy; Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; 6Medical Oncology, Policlinico Umberto I, Rome, Italy Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Janssen; Advisory/Consultancy: Merck; Advisory/Consultancy, Speaker Bureau/Expert Background: Pembrolizumab is approved in monotherapy for the first- testimony: Merck Sharp & Dohme; Advisory/Consultancy, Speaker Bureau/ Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert line (1L) of advanced or metastatic NSCLC patients (pts) with PD-L1 testimony: Pfizer; Advisory/Consultancy: Puma Biotechnology; Advisory/ ≥50%. Despite long-term survival, about one third of patients Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: experience detrimental survival outcomes, including early death, Sanofi Genzyme; Advisory/Consultancy, Speaker Bureau/Expert testimony: hyperprogression and fast progression (FP). The impact of clinical Takeda; Speaker Bureau/Expert testimony: Medscape; Speaker Bureau/Expert testimony: PeerVoice; Speaker Bureau/Expert testimony: Springer; Speaker factors on the development of FP has not been widely evaluated, so far. Bureau/Expert testimony: Touch Independent Medical Education; Speaker Methods: We designed a retrospective, multicenter study, involving 5 Bureau/Expert testimony: CME Outfitters; Speaker Bureau/Expert testimony: Italian centers, with the primary objective of investigating the clinical Prime Oncology; Research grant/Funding (institution), Grant for Oncology features associated with FP in pts with metastatic NSCLC with PD-L1 Innovation: Fundacion Merck Salud; Officer/Board of Directors, Independent ≥ member of the board: Grifols. D. Vicente Baz: Honoraria (self ), Advisory/ 50%, treated with Pembrolizumab in 1L setting. FP was defined as PD Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self ), (per investigator) within 12 weeks. Baseline clinical factors of pts with Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; and without FP were collected and analyzed. Logistic regression was Honoraria (self ), Advisory/Consultancy, Travel/Accommodation/Expenses: performed to identify clinical factors associated to FP. A FP prognostic Roche; Honoraria (self ), Advisory/Consultancy, Travel/Accommodation/ Expenses: Merch Sharp & Dohme. S. Ponce Aix: Advisory/Consultancy, Speaker score was developed based on the logistic model. Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Results: Overall, 321 out of 336 NSCLC pts treated with 1L Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck; Advisory/ pembrolizumab had completed data for analysis. FP occurred in 137 Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/ (42.7%) pts. Female sex, ECOG PS 1 or 2, concomitant steroids, tumor Expenses: Roche; Travel/Accommodation/Expenses: AstraZeneca. O. Juan-Vidal: ≥ Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; burden, 2 metastatic sites and the presence of liver/bone/pleural mets Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; were significantly associated with higher risk of FP at univariate analysis. Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/ Sex, ECOG PS, steroids, metastatic sites ≥ 2, and the presence of liver/ Accommodation/Expenses: Merck Sharp & Dohme; Advisory/Consultancy, pleural mets were confirmed as independent factors for FP at Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche/ Genentech; Advisory/Consultancy, Speaker Bureau/Expert testimony: multivariate analysis. By combining these factors, we developed a FP AstraZeneca; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Pfizer; prognostic score ranged 0–13, with three-risk group stratification: 0–2 Advisory/Consultancy: Takeda; Advisory/Consultancy: Eli Lilly. Z. Szalai: (good prognosis), 3–6 (intermediate prognosis), 7–13 (poor prognosis). Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Boehringer The AUC of the model was 0.76 (95% CI: 0.70–0.81). Ingelheim; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: GlaxoSmithKline. A. Calles Blanco: Honoraria (self ), Advisory/Consultancy: April 2021 Abstracts S755

Results: Table 104P

Scoring assignment: 0 point: ECOG PS 0 | male gender | ≤1 metastatic site | no corticosteroids | neither pleural nor liver mets 1 point: ECOG PS 1 2 points: ≥2 Table 105P: Characteristics and rwToT for 890 eligible patients metastatic sites | female gender | use of corticosteroids | pleural mets | liver mets 3 ECOG 0–1ECOG2 points: ECOG PS 2 N (%) 684 (77) 206 (23) PFS <3 months Total Men, n (%) 345 (50) 102 (50) – – no yes Age, median (range), years 72 (38 84) 75 (48 84) Positive smoking history, n (%) 632 (92) 197 (96) Score 0–2 Count 76 14 90 History of brain metastasis, n (%) 62 (9) 21 (10) % 84,4% 15,6% 100,0% NSCLC histology: Nonsquamous/ 494 (72) 152 (74) 3–6 Count 92 70 162 not otherwise specified, n (%) % 56,8% 43,2% 100,0% Patient follow-up, median (IQR), mo 17.6 (6.9–28.8) 6.3 (1.3–17.6) 7–13 Count 16 53 69 Median rwToT in months (95% CI) 7.4 (6.3–8.5) 2.8 (1.5–3.5) % 23,2% 76,8% 100,0% On-treatment rate, % (95% CI) Total Count 184 137 321 At 12 months 37.4% (33.7–41.1) 22.9% (17.2–29.0) % 57,3% 42,7% 100,0% At 24 months 22.9% (19.5–26.5) 11.1% (6.7–16.6) At 36 months 15.5% (11.9–19.5) 5.6% (2.1–11.7) Data cutoff Sept. 30, 2020; IQR, Conclusions: We identified 6 clinical factors independently associated interquartile range with FP and we developed a prognostic score model for FP-risk to potentially improve clinical practice and selection for 1L pembrolizumab in NSCLC with high PD-L1 (≥50%), in real-world clinical setting. Conclusions: Patients with key trial-eligible characteristics (ECOG 0–1, Legal entity responsible for the study: The authors. PD-L1 TPS ≥50%, EGFR/ALK negative) experienced rwToT with first- Funding: Has not received any funding. line pembrolizumab similar to the phase III pivotal clinical trial. Disclosure: A. Passaro: Advisory/Consultancy: AstraZeneca; Advisory/ Approximately 23% received at least 2 years of treatment, suggesting Consultancy: Roche Genentech; Advisory/Consultancy: Bristol-Myers Squibb; long-term benefit of pembrolizumab monotherapy for PD-L1 TPS ≥50% Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Boehringer advanced NSCLC in a real-world setting. Ingelheim; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Janssen. All Editorial acknowledgement: Editorial assistance was provided by other authors have declared no conflicts of interest. Elizabeth V. Hillyer, DVM (freelance); this assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., 105P Kenilworth, NJ, USA. Real-world time on treatment (rwToT) with first-line Legal entity responsible for the study: Merck Sharp & Dohme Corp., a pembrolizumab monotherapy in PD-L1 TPS ≥50% advanced subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. NSCLC: 3-year follow-up data Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. 1 2 2 2 2 1 Disclosure: V. Velcheti: Advisory/Consultancy: Merck; Advisory/Consultancy: V. Velcheti ,X.Hu ,Y.Li , T. Burke , B. Piperdi New York University Bristol-Myers Squibb; Advisory/Consultancy: Genentech; Advisory/Consultancy: 2 School of Medicine, New York, NY, USA; Merck & Co., Inc., Kenilworth, NJ, USA AstraZeneca; Advisory/Consultancy: Celgene; Advisory/Consultancy: Novartis; Advisory/Consultancy: Amgen; Advisory/Consultancy: Fulgent Genetics; Background: Time on treatment, also called time to treatment Advisory/Consultancy: Reddy Labs; Advisory/Consultancy: Alkermes; Advisory/ discontinuation, is a readily available real-world effectiveness endpoint Consultancy: Nektar Therapeutics; Advisory/Consultancy: Foundation Medicine. highly correlated at the patient-level with progression-free survival and X. Hu: Full/Part-time employment: MSD/Merck. Y. Li: Full/Part-time employment: MSD/Merck; Shareholder/Stockholder/Stock options: Merck. T. Burke: Full/Part- moderately to highly correlated with overall survival in clinical trials and time employment: MSD/Merck; Shareholder/Stockholder/Stock options: Merck. real-world data. In October 2016, pembrolizumab received FDA approval B. Piperdi: Full/Part-time employment: MSD/Merck; Shareholder/Stockholder/ based on results from KEYNOTE-024, as a first-line monotherapy for Stock options: Merck. patients with metastatic NSCLC with PD-L1 tumor proportion score (TPS) ≥50%andnoEGFR/ALKgenomicaberrations,administereduntildisease progression, unacceptable toxicity, or up to 24 months. In KEYNOTE-024, 106P 25% (39/154) of patients received 35 cycles (2 years) of pembrolizumab Predicting response to pembrolizumab in metastatic non- as initially assigned therapy. Our objective was to describe rwToT with small cell lung cancer (NSCLC): Clinical usefulness of first-line pembrolizumab in real-world oncology practice. peripheral lymphocyte-monocyte ratio and baseline FDG- Methods: Using the US nationwide Flatiron Health electronic health record-derived, de-identified database, we included adult patients with uptake ≥ pathologically confirmed advanced, PD-L1 TPS 50% NSCLC who 1 2 2 1 3 initiated first-line pembrolizumab monotherapy from November 2016- L. Raimondi , M. Montebello , F. Corica , P. Ciracì , G.P. Spinelli 1Oncologia Medica, Policlinico Umberto I - UniversitàLa Sapienza, Rome, September 2019, with follow-up through September 2020. Eligibility 2 – ≥ Italy; Medicina Nucleare, Policlinico Umberto I - UniversitàLa Sapienza, criteria included ECOG performance status 0 2, PD-L1 TPS 50%, no 3 EGFR/ALK genomic aberration, and no known ROS1 aberration. Patients Rome, Italy; Distretto 1 ASL Latina, Oncologia Universitaria ASL Aprilia, enrolled in a clinical trial were excluded. Median rwToT and landmark Aprilia, Italy on-treatment rates were estimated using Kaplan-Meier method. Background: Despite Pembrolizumab is the new standard of care in metastatic NSCLC with PD-L1 >50%, it was recognized not all patients benefit from it. PET imaging plays an important role in assessing the biologic behavior of NSCLC and defining response to therapy. We explored the predictive values of both the lymphocyte-monocyte ratio (LMr) in peripheral blood and baseline SUVmax of 18F-fluorodeoxyglucose by the primary tumor in positron emission tomography/computed tomography (PET/CT) in patients with metastatic NSCLC treated with Pembrolizumab. S756 Journal of Thoracic Oncology Vol. 16 No. 4S

Methods: Between January 2018 and December 2020, 203 newly Results: 34 patients treated with first line-pembro and 40 patients diagnosed metastatic NSCLC patients treated with Pembrolizumab as treated with EGFR TKI were included. We selected 75 cm3 as cutoff with first line therapy were recruited. The optimal cut-off values for baseline ROC curve (sensitivity 87%, specificity 71%). In the pembro group, SUVmax and peripheral LMr were determined by ROC curves. The median follow up was 20.3 months, median OS 4.7 months (95% CI 0.3– predictive values of SUVmax and LMr were examined by X-square and 9.1) for pts with tMTV ≥75 cm3 vs Not Reached (NR) for pts with tMTV Fisher’s exact tests; survival functions using the Kaplan–Meier. Log‐rank <75 cm3 (95% CI NR – NR. HR 5.37; 95% CI 1.72–16.77; p0.004). test and Cox regression were used for statistical comparisons between No difference was found in the control group (HR 1.43; 95% CI 0.61– curves. 3.34; p 0.411). Results: The objective response rate (ORR) was significantly different between the high-SUVmax group and the low-SUVmax group (53% vs Table 107P 87.1%; P = 0.003), as well as between the high-LMR group and the low- LMR group (93.1% vs 45.2%; P = 0.001). We stratified patients by low or Univariate analysis Multivariate analysis high SUVmax and LMr >5.2 or >5.2 into 3 groups with different levels of HR 95% CI p HR 95%CI p risk of relapse. The low risk level (low-SUVmax and high-LMR; n = 120, ≥ 3 59%) had a 3‐year PFS of 85% (95% CI: 78–95%), the intermediate level tMTV 75 cm 5.37 1.72 16.77 0.004 9.28 2.00 43.15 0.005 SUV max on primitive lesion 1.00 0.98 1.10 0.198 (high-SUVmax or LMr >5.2; n = 27, 13%) had a 3‐year PFS of 67% (95% – (continuous variable) CI: 55 79%), and the high risk level (high-SUVmax and LMr >5.2; n = 56, SUVmax of the whole exam 1.03 0.98 1.07 0.246 ‐ – ‐ 28%) had a 3 year PFS of 10% (95% CI: 1 29%). The log rank test Neutrophil/lymphocyte 5.35 1.79 15.98 0.003 7.51 1.73 32.54 0.007 between the intermediate and low levels and between the high and ratio ≥4 intermediate levels were significant (P = 0.006, P < 0.001, respectively). LDH >ULN 3.92 1.33 11.50 0.013 1.75 0.51 6.03 0.374 For OS, the difference between the high and intermediate/low levels was ECOG PS ≥2 3.08 1.14 8.32 0.027 6.58 1.75 24.77 0.005 significantly different (P < 0.001). Presence of liver metastasis 2.57 0.81 8.12 0.109 1.48 0.31 7.19 0.627 Conclusions: By combining baseline SUVmax of the primary tumor and Presence of bone metastasis 1.86 0.72 4.76 0.201 the peripheral LMr, we may identify metastatic NSCLC in treatment with Pembrolizumab with poor PFS and OS and who more likely may have a ≥ 3 better primary tumor response to Pembrolizumab. Conclusions: TMTV 75 cm can be used as predictor of poor outcome Legal entity responsible for the study: The authors. in aNSCLC PDL1-high pts treated with first line pembro. These pts may Funding: Has not received any funding. require the addition of chemotherapy to pembro. ’ Disclosure: All authors have declared no conflicts of interest. Legal entity responsible for the study: Filippo G. Dall Olio. Funding: AIRC - Fondazione AIRC per la Ricerca sul Cancro (investigator grant 19026). Disclosure: A. Ardizzoni: Advisory/Consultancy: BMS; Advisory/Consultancy: 107P AstraZeneca; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: MSD; Baseline total metabolic tumour volume on [18F]FDG PET/CT Advisory/Consultancy: Roche. All other authors have declared no conflicts of as promising biomarker in advanced NSCLC patients treated interest. with first line pembrolizumab

F.G. Dall’Olio1, D. Calabrò2, N. Conci3, G. Argalia2, P. Marchese3, 108P F. Fabbri3, B. Fragomeno3, S. Fanti2, V. Ambrosini2, A. Ardizzoni4 Real-world time on treatment (rwToT) analysis for first-line 1Dipartimento di Oncologia Medica, AOU Policlinico S. Orsola-Malpighi, pembrolizumab combination therapy in advanced Bologna, Italy; 2Nuclear Medicine, Department of Experimental, nonsquamous NSCLC Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; 3Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, S.V. Liu1,X.Hu2,Y.Li2, T. Burke2, B. Piperdi2 1Medical Oncology 4 Bologna, Italy; Department of Experimental, Diagnostic and Specialty Department, Lombardi Cancer Center Georgetown University, Medicine - Dimes, University of Bologna, Bologna, Italy Washington, DC, USA; 2Merck & Co., Inc., Kenilworth, NJ, USA Background: Immune Checkpoint Inhibitors (ICI) have become Background: Pembrolizumab plus pemetrexed and platinum (pembro standard of care in the management of advanced non-small cell lung combo) is the preferred first-line regimen in US treatment guidelines for cancer (aNSCLC). Nevertheless, only a small proportion of patients (pts) advanced nonsquamous NSCLC without actionable genomic aberrations benefit from ICI. Diverse biomarkers have been proposed but none of and independent of PD-L1 tumor proportion score (TPS). Time on them appears to be the “ultimate biomarker.”Aim of the present study is treatment (ToT) is a surrogate real-world effectiveness endpoint to assess whether [18F]FDG-PET/CT derived parameters may be used demonstrating high correlation to progression-free survival and as biomarkers in aNSCLC patients receiving first-line pembrolizumab. moderate-to-high correlation to overall survival. Our aim was to evaluate Methods: This is a monocentric retrospective cohort study including pts rwToT with first-line pembro combo in patients with advanced with aNSCLC (stage IV) and PD-L1 expression ≥50% treated with nonsquamous NSCLC. pembrolizumab within clinical practice. A control group of pts treated Methods: Adult patients initiating first-line pembro combo (June 2017- with EGFR inhibitors for EGFR mutated NSCLC was also enrolled. Only September 2019) were selected from the US nationwide Flatiron Health patients with a positive [18F]18F-FDG PET/CT performed at our center electronic health record-derived, de-identified database. Patients within 60 days from treatment initiation were included. Total Metabolic included in the analysis had nonsquamous NSCLC, stage IIIB or IV Tumor Volume (tMTV) was calculated for each lesion by a dedicated disease or recurrent disease, wild-type EGFR/ALK, no known ROS1 software (PET VCAR, GE Healthcare) on transaxial PET images, that fusion, and an ECOG performance status of 0–1, excluding those in semi-automatically delineates the tumour’s contours with a SUVmax therapeutic clinical trials. Median rwToT and on-treatment rates were threshold of 42% within the lesion. TMTV was obtained summing each estimated using the Kaplan-Meier method, with follow-up through single lesion’s MTV. Potential prognostic parameters for OS were September 2020. analysed (TMTV, SUVmax, presence of bone/liver mets, neutrophil/ lymphocyte ratio ≥ 4, ECOG PS ≥ 2, LDH > ULN). April 2021 Abstracts S757

Table 108P: rwToT and on-treatment rates for pembrolizumab and pemetrexed 109P Real-world evaluation of pembrolizumab monotherapy for PD-L1 TPS ≥50% PD-L1 TPS 1–49% PD-L1 TPS <1% N = 222 N = 282 N = 246 PD-L1 positive (TPS>50%) metastatic NSCLC in France

Pembro rwToT, median 10.0 (7.9–12.2) 6.2 (4.9–6.9) 4.9 (3.9–5.7) ́ 1 2 3 4 5 (95% CI), mo M. Perol , T. Filleron , X. Quantin , C. Chouaid , C. Audigier Valette , 6 7 8 9 10 Pembro on-treatment H. Lena , C. Kaderbhai , C. Fabre , M. Santorelli , L. Bensimon , rates, % (95% CI): T. Burke11, D. Couch12, E. Nguyen12, C. Courtinard12, At 12 months 44.4% (37.6–51.0) 28.6% (23.3–34.2) 24.5% (19.1–30.2) ESME Lung Cancer Group12 1Medical Oncology Dept., Centre Leoń At 24 months 26.0% (19.3–33.3) 17.2% (12.3–22.9) 11.7% (7.3–17.3) ́ 2 Pemetrexed rwToT, 3.5 (2.6–4.3) 3.4 (2.6–3.7) 3.3 (2.4–3.7) Berard, Lyon, France; Biostatistics, Centre Claudius-Regaud, Toulouse, 3 median (95% CI), mo France; ICM Regional Cancer Institute of Montpellier, Montpellier, Pemetrexed on-treatment, France; 4CH Intercommunal de Creteil,́ Creteil,́ France; 5Hopital Sainte % (95% CI): Musse, Toulon, France; 6CHU de Pontchaillou, Rennes, France; 7Centre At 12 months 21.1% (15.9–26.9) 20.2% (15.5–25.2) 13.0% (8.9–17.7) 8 At 24 months 3.3% (1.0–7.9) 9.9% (6.1–14.8) 5.7% (2.9–9.8) Georges Francois Leclerc, Dijon, France; Capionis, IQVIA Company 9 10 Data cutoff Sept. 30, 2020; (France), Courbevoie, France; Merck & Co, Rahway, NJ, USA; Dir ass. mo, months Evaluation Medico-Economiqué et Epidemiologique, MSD France, Puteaux, France; 11Merck & Co., Inc., Kenilworth, NJ, USA; 12Data Office, UNICANCER, Paris, France Results: The median patient follow-up duration for this cohort was 15.3 months (range: 1 day to 40 months). Baseline cohort characteristics Background: Pembrolizumab was the first anti-PD-1 therapy approved were similar: median age was 66–69 years (overall range, 34–84); 55– for previously untreated metastatic NSCLC in Europe, based on results 57% were men. Median rwToT was 10.0 months for patients with PD-L1 from the KEYNOTE-024 trial where the Kaplan-Meier (KM) estimated TPS ≥50%, 6.2 months with TPS 1–49%, and 4.9 months with TPS <1%. 12-month overall survival was 70.3%. Our aim was to estimate overall In the PD-L1 TPS ≥50% cohort, 26% of patients remained on survival (OS) and real-world progression-free survival (rwPFS) in pembrolizumab at 2 years. France for pembrolizumab monotherapy as first-line treatment for Conclusions: The rwToT with pembrolizumab increased with PD-L1 patients with metastatic NSCLC and PD-L1 tumor proportion score (TPS) ≥ TPS level, although the rwToT with pemetrexed in each cohort was 50%. substantially shorter. A considerable proportion of patients remained on Methods: Using the Epidemiological Strategy Medical Economics pembrolizumab at 2 years, suggesting long-term benefit. Advanced or Metastatic Lung Cancer (ESME-AMLC) Data Platform Editorial acknowledgement: Editorial assistance was provided by [NCT03848052], we identified adult patients with histologically ≥ Elizabeth V. Hillyer, DVM (freelance); this assistance was funded by confirmed metastatic, PD-L1 TPS 50% NSCLC initiating first-line Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., pembrolizumab monotherapy treatment between 12 May 2017 and 31 Kenilworth, NJ, USA. December 2018. Patients with EGFR/ALK genomic aberration or who Legal entity responsible for the study: Merck Sharp & Dohme Corp., a enrolled in a clinical trial were excluded. This planned interim analysis subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA was based on a pre-specified statistical analysis plan, with data cut-off on Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., August 31, 2019. OS and rwPFS were estimated using the KM method. Kenilworth, NJ, USA. Results: A total of 164 patients were included, with 8 months median Disclosure: S.V. Liu: Advisory/Consultancy: Amgen; Advisory/Consultancy, follow-up (range: 0, 24). ECOG performance status (PS) at treatment Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: initiation was 0–1 (n = 86, 68.3%), 2 (n = 25, 19.8%), 3–4 (n = 15, Beigene; Research grant/Funding (institution): Alkermes; Research grant/ 11.9%%), or missing (n = 38). Additional patient characteristics and OS/ Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding rwPFS results are shown below. (institution): Blueprint; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Corvus; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: G1 Therapeutics; Table 109P Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Inivata; Overall ECOG PS 0–1 Advisory/Consultancy: Janssen; Advisory/Consultancy: Jazz Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Research N 164 86 grant/Funding (institution): Lycera; Advisory/Consultancy, Research grant/ Men, n (%) 114 (69.5) 54 (62.8) Funding (institution): Merck/MSD; Research grant/Funding (institution): Merus; Age, median (range), yr 65 (39, 91) 62.5 (42, 91) Advisory/Consultancy: PharmaMar; Advisory/Consultancy, Research grant/ Current/former smoker, n (%) 146 (89.0) 78 (90.7) Funding (institution): Pfizer; Research grant/Funding (institution): Rain Non-squamous histology, n (%) 132 (80.5) 70 (81.4) Therapeutics; Research grant/Funding (institution): RAPT; Advisory/ Brain metastasis, n (%) 42 (25.6) 23 (26.7) Consultancy: Regeneron; Research grant/Funding (institution): Spectrum; Median OS in months (95% CI) NR NR Advisory/Consultancy: Takeda; Research grant/Funding (institution): Turning OS rate, % (95% CI) Point Therapeutics. X. Hu: Full/Part-time employment: MSD/Merck. Y. Li: Full/ Part-time employment: MSD/Merck; Shareholder/Stockholder/Stock options: At 6 months 70.5 (62.6,77.0) 80.8 (70.6, 87.8) Merck. T. Burke: Full/Part-time employment: MSD/Merck; Shareholder/ At 12 months 58.6 (49.8, 66.4) 67.9 (55.9, 77.2) Stockholder/Stock options: Merck. B. Piperdi: Full/Part-time employment: MSD/ Median rwPFS in months, (95% 3.9 (2.4, 6.4) 7.2 (3.7, 9.9) Merck; Shareholder/Stockholder/Stock options: Merck. CI) rwPFS rate, % (95% CI) At 6 months 43.6 (35.7,51.2) 53.6 (42.4, 63.6) At 12 months 28.4 (21.1, 36.2) 34.3 (23.5, 45.3)

Conclusions: Clinical outcomes among metastatic NSCLC patients with high PD-L1 expression were consistent with those of KEYNOTE-024, supporting the effectiveness of pembrolizumab in the real-world setting in France. Clinical trial identification: ESMECSM2019–24. Legal entity responsible for the study: UNICANCER. Funding: MSD. S758 Journal of Thoracic Oncology Vol. 16 No. 4S

Disclosure: M. Perol:́ Advisory/Consultancy, Advisory Boards/Symposium/ Institutional grants: Roche; Advisory/Consultancy, Advisory Boards/Symposium: Table 110P Eli Lilly; Advisory/Consultancy, Advisory Boards/Symposium: Novartis; Overall ECOG 0–1ECOG≥2 Advisory/Consultancy, Advisory Boards/Symposium/Institutional grants: AstraZeneca; Advisory/Consultancy, Advisory Boards/Symposium/Institutional N 304 131 63 grants: Takeda; Advisory/Consultancy, Advisory Boards/Symposium: MSD; Age, median (range), yr 62.5 (37, 92) 62 (37, 92) 63 (42, 85) Advisory/Consultancy, Advisory Boards/Symposium: Bristol-Myers Squibb; Current/former smoker, n 276 (90.8) 122 (93.1) 55 (87.3) Advisory/Consultancy, Advisory Boards/Symposium/Institutional grants: (%) Boehringer-Ingelheim; Advisory/Consultancy, Advisory Boards/Symposium: Pfizer; Advisory/Consultancy, Symposium: Amgen; Advisory/Consultancy, Non-squamous histology, 261 (85.9) 112 (85.5) 54 (85.7) Symposium/Institutional grants: CHUGAU; Advisory/Consultancy, Symposium: n (%) Illumina. T. Filleron: Research grant/Funding (institution): BMS. All other authors History of brain 120 (39.5) 49 (37.4) 25 (39.7) have declared no conflicts of interest. metastasis, n (%) TPS 1–49% 147 (51.0) 56 (43.8) 29 (50.9) ≥50% 141 (49.0) 72 (56.3) 28 (49.1) 110P NR 16 3 6 Real-world evaluation of pembrolizumab monotherapy for Median OS, mos. (95% CI) 13.7 (9.9, NR) 16.2 (10.2, NR) 5.4 (2.8, NR) previously treated PD-L1 positive (TPS>1%) advanced NSCLC OS rate, % (95% CI) in France 12 mos 52.9 (45.9, 55.5 (44.7, 38.0 (24.1, 59.5) 65.0) 51.7) Median rwPFS, mos. (95% 2.8 (2.1, 3.7) 3.3 (2.3, 5.7) 1.4 (1.4, 2.6) M. Pérol1, X. Quantin2, H. Lena3, T. Filleron4, C. Chouaid5, 6 7 8 9 CI) C. Audigier Valette , C. Kaderbhai , G. Chenuc , M. Santorelli , rwPFS rate, % (95% CI) 10 11 12 12 L. Bensimon , T. Burke , G. Simon , A-L. Martin , 12 mos 21.6 (16.3, 24.3 (16.1, 12.1 (4.1, 24.8) 13 14 15 16 D. Debieuvre , R. Gervais , R. Schott , M. Carton , 27.4) 33.3) C. Courtinard12, N. Girard17, ESME Lung Cancer Group12 1Medical Oncology Dept, Centre Leoń Berard,́ Lyon, France; 2ICM Regional Cancer 3 Institute of Montpellier, Montpellier, France; CHU de Pontchaillou, Conclusions: Clinical outcomes among previously treated advanced, 4 Rennes, France; IUCT Oncopole, Centre Claudius-Regaud, Toulouse, PD-L1 expressing NSCLC patients were consistent with clinical trial 5 6 France; CH Intercommunal de Creteil,́ Creteil,́ France; Hopital Sainte results thus supporting the effectiveness of pembrolizumab in the real- 7 Musse, Toulon, France; Centre Georges Francois Leclerc, Dijon, France; world setting in France. 8 9 Capionis, IQVIA Company (Frab, Courbevoie, France; Merck & Co, Clinical trial identification: ESMECSM2019–24. 10 Rahway, NJ, USA; Dir ass. Evaluation Medico-Economiqué et Legal entity responsible for the study: UNICANCER. 11 Epidemiologique,́ MSD France, Puteaux, France; Merck & Co., Inc., Funding: MSD. 12 13 Kenilworth, NJ, USA; Data Office, UNICANCER, Paris, France; GH Disclosure: M. Perol:́ Advisory/Consultancy, Advisory Boards/Symposium/ Mulhouse, Mulhouse, France; 14Centre Francois Baclesse, Caen, France; Institutional grants: Roche; Advisory/Consultancy, Advisory Boards/Symposium: 15ICANS - Institut de Cancerologié Strasbourg Europe, Strasbourg, France; Eli Lilly; Advisory/Consultancy, Advisory Boards/Symposium: Novartis; 16 17 Advisory/Consultancy, Advisory Boards/Symposium/Institutional grants: Biometry, Institut Curie, Paris, France; Thorax Institute, Institut Curie, AstraZeneca; Advisory/Consultancy, Advisory Boards/Symposium/Institutional Paris, France grants: Takeda; Advisory/Consultancy, Advisory Boards/Symposium: MSD; Advisory/Consultancy, Advisory Boards/Symposium: Bristol-Myers Squibb; Background: Information on real-world clinical outcomes for pembro- Advisory/Consultancy, Advisory Boards/Symposium/Institutional grants: lizumab monotherapy among patients with previously treated advanced Boehringer-Ingelheim; Advisory/Consultancy, Advisory Boards/Symposium: NSCLC remains limited. Our aim was to estimate overall survival (OS) Pfizer; Advisory/Consultancy, Symposium: Amgen; Advisory/Consultancy, Symposium/Institutional grants: CHUGAU; Advisory/Consultancy, Symposium: and real-world progression-free survival (rwPFS) in France for Illumina. T. Filleron: Research grant/Funding (institution): BMS. All other authors pembrolizumab monotherapy in previously treated, PD-L1-expressing have declared no conflicts of interest. advanced NSCLC patients following approval based on the phase III trial KEYNOTE-010 (KN010), where a 11.8 month median OS (95% CI: 10.4 to 13.1) and a 48.9% 12-month OS rate (95% 45.1, 52.6) were reported. 111P Methods: Using the Epidemiological Strategy Medical Economics ≥ Advanced or Metastatic Lung Cancer (ESME-AMLC) Data Platform Advanced non-small cell lung cancer with PD-L1 50%: [NCT03848052], we identified adult patients with histologically Pembrolizumab alone or combined with chemotherapy confirmed, PD-L1 TPS ≥1%, advanced (stage IIIB or IV) NSCLC treated with at least one prior chemotherapy regimen and who initiated B. Han, B. Han, B. Zhang, M. Hu, Y. Wang, Z. Yang, W. Zhang pembrolizumab monotherapy between 12 May 2017 and 31 December Department of Pulmonary Medicine, Shanghai Chest Hospital Affiliated to 2018. Patients with EGFR/ALK genomic aberration were required to Shanghai Jiao Tong University, Shanghai, China have been treated with an appropriate targeted therapy prior to Background: Pembrolizumab plus platinum-based chemotherapy (PC) pembrolizumab. Patients who received pembrolizumab in a clinical trial and pembrolizumab monotherapy (PM) both become standard of care in were excluded. This planned interim analysis was based on a pre- patients with advanced non-small cell lung cancer (NSCLC) and a specified statistical analysis plan, with data cut-off on August 31, 2019. programmed death ligand 1 (PD-L1) tumor proportion score (TPS) OS and rwPFS were estimated using the KM method. greater than 50%. This study aimed to figure out the better treatment Results: A total of 304 patients were identified, with a median follow-up choice. of 5.9 months (range: 0, 24). Patient characteristics and OS/rwPFS Methods: In this retrospective analysis, we compared the clinical results are shown below. efficacy of PM and PC as first-line treatment in NSCLC patients with a PD- L1 ≥50% and negative for genomic alterations in the EGFR and ALK genes. Results: Among the population, 115 patients received PC and 91 patients received PM. Up to Dec 30, 2020, median follow-up was 15.52 months. The median progression-free survival (PFS) of PC and PM were 12.37 and 9.60 months (HR:0.44, p <0.001), respectively. The median overall survival (OS) of PC had not reached while the OS of PM was 28.91 April 2021 Abstracts S759 months (HR:0.40, p = 0.008). Subgroup analysis found that the PFS benefit of PC was evident in most subgroups excepting patients with 113P brain metastasis. The 1-year overall survival rate of PC and PM were Comparative efficacy and safety of PD-1/PD-L1 inhibitor 89.0% and 78.3%, respectively. The ORR were 61.7% and 46.9% (p = monotherapy or in addition to chemotherapy for advanced, 0.040), respectively. PD-L1 high non-small cell lung cancer (NSCLC): A meta- Conclusions: In patients with previously untreated, PD-L1≥50%, analysis of randomized trials advanced NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard platinum-based chemotherapy should be A. Di Federico1, A. De Giglio1, G. Nuvola1, C. Deiana1, N. Conci1, recommended as the preferred treatment. C. Bonucci1, G. Donati1, C. Parisi1, F. Gelsomino2, A. Ardizzoni2 Legal entity responsible for the study: The authors. 1Department of Specialized, Experimental and Diagnostic Medicine, Funding: Has not received any funding. University of Bologna, Bologna, Italy; 2Division of Medical Oncology, IRCCS Disclosure: All authors have declared no conflicts of interest. Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy Background: PD-(L)1 inhibitors, alone and in association with chemotherapy (CT), improved the outcomes of advanced, PD-L1 high 112P non-small cell lung cancer (NSCLC) patients as compared to CT alone. Atezolizumab as first-line therapy for patients with advanced Nonetheless, no direct comparison exists between these agents. non-small cell lung cancer: A systematic review and meta- Methods: A meta-analysis of available randomized clinical trials (RCT) analysis on overall survival was performed to assess and compare efficacy and safety of PD-(L)1 inhibitor monotherapy and in addition to CT as compared to CT alone for E. Marcella1, B. Susanto1, S. Chen1, J. Tandiono1, A. Tancherla1, advanced, PD-L1 high NSCLC. R.S. Heriyanto1, F. Wijovi1, A. Kurniawan2 1Faculty of Medicine, Pelita Results: 13 RCT (6 testing immunotherapy vs CT and 7 testing the Harapan University, Tangerang, Indonesia; 2Department of Internal addition of a PD-(L)1 inhibitor to CT vs CT) were included in the analysis. Medicine, Pelita Harapan University, Tangerang, Indonesia PD-(L)1 inhibitor monotherapy significantly improved Progression-Free Background: Non-small cell lung cancer (NSCLC) is a type of lung Survival (PFS) [HR: 0.67; 95% CI, 0.60–0.75], Overall Survival (OS) [HR: cancer with a poor prognosis rate. Atezolizumab is a monoclonal 0.68; 95% CI, 0.60–0.76], and Objective Response Rate (ORR) [RR: 1.30; antibody against PD-L1 that can restore anticancer immunity & improve 95% CI, 1.16–1.46] as compared to CT. PD-(L)1 inhibitor monotherapy overall survival in patients with advanced NSCLC. This study aims to resulted to be better tolerated compared to CT, with lower incidence of evaluate the efficacy of atezolizumab versus chemotherapy as first-line grade 3–5 treatment-related adverse events (TRAEs) [RR: 0.45; 95% CI, therapy for NSCLC. 0.41–0.50]. A subgroup analysis performed according to the type of Methods: Data was collected from PMC, PubMed, Google Scholar, targeted receptor (PD-1 vs PD-L1) did not demonstrate any statistically Science Direct, and Scopus from January 4th- 5th 2020, using a significant difference in terms of PFS (p = 0.67), OS (p = 0.86) and ORR combination of keywords associated with NSCLC and treatment (p = 0.06) between PD-1 and PD-L1 inhibitors monotherapies, although using atezolizumab in relation to their overall survival & were then a significant difference (p = 0.05) in terms of grade 3–5 TRAEs in favor evaluated by 7 people to minimize bias. Inclusion criteria for studies are of PD-1 inhibitors was reported. We then used a meta-regression original clinical trials published ≥ 2015 with a study population of analysis to compare the outcomes obtained with PD-(L)1 inhibitor adults (>18 years old) in manuscripts limited to English. The quality of monotherapy or in addition to CT vs CT in the PD-L1 high population. each included study was assessed using the Newcastle-Ottawa Scale The combination strategy led to better PFS [HR: 0.60; 95% CI, 0.44–0.84; (NOS) & GRADE. p = 0.002] and ORR [RR: 1.66; 95% CI, 1.14–2.42; p = 0.008] compared Results: 11 clinical trial studies consisting of 8224 advanced NSCLC to PD-(L)1 inhibitor monotherapy, while no OS differences were patients were included. The included studies were assessed using NOS & documented [HR: 0.99; 95% CI, 0.77–1.27; p = 0.95]. were all in good quality. 6 studies showed that atezolizumab shows Conclusions: Based on this meta-analysis, PD-1 inhibitor monotherapy significant improvement in OS compared to chemotherapy as the first- might lead to better ORR and less incidence of grade 3–5 TRAEs line treatment of advanced NSCLC. 5 studies found that patients treated compared to PD-L1 inhibitor monotherapy. The combination of PD-(L)1 with atezolizumab + chemotherapy (bevacizumab, carboplatin, and inhibitor and CT led to improved PFS and ORR, but similar OS, as paclitaxel) have a more significant improvement in OS compared to compared to PD-(L)1 inhibitor monotherapy in PD-L1 high NSCLC those who are only treated with chemotherapy. Pooled analysis showed patients. that atezolizumab alone significantly improve OS (HR = 0.66; 95% CI, Legal entity responsible for the study: The authors. 0.54–0.81; p < 0.0001). Combination of atezolizumab & chemotherapy Funding: Has not received any funding. also significantly improve OS (HR = 0.75; 95% CI, 0.65–0.86; p < 0.0001) Disclosure: A. Ardizzoni: Research grant/Funding (institution): BMS; Research in comparison with chemotherapy alone. Based on GRADE, the result of grant/Funding (institution): Roche; Research grant/Funding (institution): Celgene. All other authors have declared no conflicts of interest. this systematic review & meta-analysis proved to be moderate in quality as there are no inconsistencies and variability in results & there are no publication biases. Conclusions: Atezolizumab exhibits a significant improvement in OS 114P compared to chemotherapy, and therefore may pose as a better first-line Nivolumab plus ipilimumab as first-line treatment for patients treatment option for patients with advanced NSCLC. Studies also found with advanced non-small cell lung cancer: A systematic that atezolizumab combined with chemotherapy is the best treatment review option, with remarkable efficacy and manageable safety profile. Legal entity responsible for the study: The authors. J. Tandiono1, S. Chen1, E. Marcella1, B. Susanto1, R.S. Heriyanto1, Funding: Has not received any funding. F. Wijovi1, A. Tancherla1, A. Kurniawan2 1Faculty of Medicine, Pelita Disclosure: All authors have declared no conflicts of interest. Harapan University, Tangerang, Indonesia; 2Department of Internal Medicine, Pelita Harapan University, Tangerang, Indonesia Background: Nivolumab is a type of immunotherapy consisting of human IgG4 monoclonal antibody that blocks Programmed cell Death Protein-1 (PD-1). Meanwhile, ipilimumab is also a monoclonal antibody S760 Journal of Thoracic Oncology Vol. 16 No. 4S medication used to target Cytotoxic T-Lymphocyte-Associated protein-4 monotherapy. Here, we present follow-up data including survival (CTLA-4). Nivolumab and ipilimumab both show significant improve- outcomes not previously reported. ment in overall survival in the treatment of advanced non-small cell lung Methods: Pts received cemiplimab 350 mg every 3 weeks (Q3W) (Arm cancer (NSCLC). This study aims to assess the efficacy of nivolumab plus A); or cemiplimab 350 mg Q3W plus ipilimumab 50 mg every 6 weeks ipilimumab as first line treatment for patients with advanced NSCLC. (Arm B); or cemiplimab 1050 mg Q3W (Arm C), for up to 108 weeks or Methods: On January 6th 2020, data was collected from PMC, PubMed, until progression. Primary endpoint was ORR per independent review Google Scholar, Science Direct, and Scopus, using combination of committee (IRC). Data cut-off was 30 Jun 2020. keywords associated with advanced NSCLC & treatment using nivolu- Results: Of 28 pts enrolled, 27 received treatment (Arm A, n = 8; Arm B, n mab plus ipilimumab as first line treatment. Publication are published = 11; and Arm C, n = 8). Median duration of treatment exposure was 10.8 ≥2014 with English manuscripts, were all evaluated by the authors. All (Arm A), 17.9 (Arm B) and 10.8 (Arm C) weeks. Median follow-up was 2.6 the studies had an inclusion criteria of any patient ≥18 years old & (Arm A), 17.4 (Arm B) and 3.9 (Arm C) months. ORR (95% confidence exclusion criteria of any patient with autoimmune disease. The quality of interval [CI]) remained unchanged since the previous report: 0% (0.0– each included studies was assessed using the Newcastle-Ottawa Scale 36.9%) in Arm A, 45.5% (16.7–76.6%) in Arm B, and 11.1% (0.3–48.2%) (NOS). in Arm C, with a median duration of response not reached (NR) in Arm B Results: A total of 8 studies consisting of 7 clinical trials & 1 cohort with and 11.2 months in Arm C. Median overall survival (OS) (95% CI) per IRC a total of 7443 advanced NSCLC patients were included. All included was 5.1 months (1.7–not evaluable [NE]) in Arm A, NR (2.2–NE) in Arm B studies were assessed using NOS, revealing 6 studies of good quality & 2 and 8.4 months (0.3–NE) in Arm C. Median progression-free survival studies of moderate quality. 7 studies yield that compared to (PFS) (95%CI) perIRC was 2.0 months (0.7–8.3) in Arm A, NR (1.2–NE) in chemotherapy, nivolumab plus ipilimumab is proven to be superior & Arm B and 1.8 months (0.3–12.7) in Arm C. Grade ≥3 treatment-emergent more beneficial. 1 study proved greater objective response rate (ORR), 2 adverse events (AEs) occurred in 25.0% (Arm A), 72.7% (Arm B) and studies presented improvement in overall survival, 1 study revealed 75.0%(ArmC) of pts.Acrossall arms,increasedalanineaminotransferase greater progression-free survival rate, & 3 studies unveiled good safety was the only Grade ≥3 immune-related AE reported in >1 pt (n = 2 profile & encouraging clinical activity & improvement in nivolumab plus [18.2%]; both in Arm B). ipilimumab. 1 study also proved nivolumab plus ipilimumab showed Conclusions: This follow-up analysis which includes OS/PFS data shows greater improvement compared to nivolumab plus chemotherapy. that combination of ipilimumab 50 mg with cemiplimab 350 mg Conclusions: Nivolumab plus ipilimumab had shown significant provides additional survival improvement in pts with advanced NSCLC improved benefits when treating patients with advanced NSCLC and PD-L1 <50%. Moreover, consistency in ORR with the previous compared to chemotherapy. It demonstrates good safety profile, efficacy, analysis demonstrates durability of responses to cemiplimab 350 mg + and clinical improvement despite a longer duration of exposure. ipilimumab 50 mg. Therefore, nivolumab and ipilimumab should be greatly considered as Clinical trial identification: NCT03430063. first-line therapy in treatment of advanced NSCLC patients. Editorial acknowledgement: Medical writing support was provided by Legal entity responsible for the study: The authors. Atif Riaz, PhD of Prime, Knutsford, UK, funded by Regeneron Funding: Has not received any funding. Pharmaceuticals, Inc. and Sanofi. Disclosure: All authors have declared no conflicts of interest. Legal entity responsible for the study: Regeneron Pharmaceuticals, Inc. and Sanofi. Funding: Regeneron Pharmaceuticals, Inc. and Sanofi. 115P Disclosure: S. Lee: Shareholder/Stockholder/Stock options, Full/Part-time employment: Regeneron Pharmaceuticals, Inc. J. de Castro Carpeño: Advisory/ Survival data from EMPOWER-Lung 4: Phase II study of Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/ cemiplimab plus ipilimumab in the second-line (2L) treatment Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Bristol-Myers of advanced non-small cell lung cancer (NSCLC) Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: Hoffmann-la Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp 1 2 3 4 5 and Dohme; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; B.Y. Shim , S. Lee , J. de Castro Carpeño , C-H. Chiu , M. Cobo , Advisory/Consultancy: Takeda. M. Majem Tarruella: Advisory/Consultancy, H.R. Kim6, J.S. Ryu7, M. Majem Tarruella8, Y. Summers9, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: C.A. Thomas10,Y.Xu2,I.Lowy2, P. Rietschel2 1Department of Medical Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (self ), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: Oncology, St. Vincent’s Hospital, College of Medicine, The Catholic 2 Kyowa Kirin; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck University of Korea, Suwon, Republic of Korea; Regeneron Sharp & Dohme; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy, Pharmaceuticals, Inc., Tarrytown, NY, USA; 3Department of Oncology, Travel/Accommodation/Expenses: Roche. Y. Summers: Advisory/Consultancy: Hospital Universitario La Paz, Madrid, Spain; 4Department of Chest Bristol-Myers Squibb. Y. Xu: Shareholder/Stockholder/Stock options, Full/Part- time employment: Regeneron Pharmaceuticals, Inc. I. Lowy: Shareholder/ Medicine, Taipei Veterans General Hospital/School of Medicine, National 5 Stockholder/Stock options, Full/Part-time employment: Regeneron Yang-Ming University, Taipei, Taiwan; Unidad de GestionCĺ ınicá Pharmaceuticals, Inc. P. Rietschel: Shareholder/Stockholder/Stock options, Full/ Intercentros de OncologıaMé dica,́ Hospitales Universitarios Regional y Part-time employment: Regeneron Pharmaceuticals, Inc. All other authors have Virgen de la Victoria, IBIMA, Malaga, Spain; 6Division of Medical declared no conflicts of interest. Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea; 7Department of Internal Medicine, Inha University Hospital, Incheon, Republic of Korea; 8Servicio de Oncologıá Medica,́ Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 9Department of Medical Oncology, The Christie NHS Foundation Trust/ Division of Cancer Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK; 10New England Cancer Specialists, Scarborough, ME, USA Background: EMPOWER-Lung 4 is a phase II study evaluating cemiplimab monotherapy, and combination therapy with cemiplimab + ipilimumab, as 2L treatment in patients (pts) with advanced NSCLC and programmed cell death-ligand 1 (PD-L1) <50%. We previously reported on this study, showing that numerically better objective response rates (ORR) were observed with cemiplimab + ipilimumab vs cemiplimab April 2021 Abstracts S761

116P 117P Real-world outcomes of patients with metastatic non-small Family history of cancer and improved outcomes with first- cell lung cancer receiving 2L+ atezolizumab-based line immunotherapy in NSCLC patients treatments in Taiwan clinical practice A. Cortellini1, S. Buti2, M. Di Maio3, R. Giusti4, O. Nigro5, L. Cantini6, S-G. Wu1, C-L. Chiang2, C-C. Wang3, J-Y. Hung4, T-C. Hsia5,C-Y.Su6, E. Bria7, F. Grossi8, M. Torniai9, M. De Tursi10, F. Citarella11, C-F. Chen6, C-H. Kuo7, J-Y. Shih1 1Internal Medicine Department, F. Mazzoni12, A.J. Gelibter13, M. Macerelli14, M.R. Migliorino15, National Taiwan University Hospital, Taipei, Taiwan; 2Chest Medicine, A. Russo16, A. Addeo17, G. Porzio18, C. Ficorella19, D.J. Pinato20 Taipei Veterans General Hospital, Taipei, Taiwan; 3Department of 1Department of Surgery and Cancer, Imperial College London, London, Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, UK; 2Medical Oncology, University Hospital of Parma, Parma, Italy; Kaohsiung, Taiwan; 4Faculty of Medicine, College of Medicine, Kaohsiung 3Department of Oncology, University of Turin, Turin, Italy; 4Medical Medical University, Kaohsiung, Taiwan; 5Department of Internal Medicine, Oncology, St. Andrea Hospital of Rome, Rome, Italy; 5Medical Oncology, China Medical University Hospital, Department of Respiratory Therapy, ASST-Sette Laghi, Varese, Varese, Italy; 6Department of Pulmonary China Medical University, Taichung, Taiwan; 6Medical Division, Roche Disease, Erasmus Medical Center, Rotterdam, Netherlands; Products Ltd, Taipei, Taiwan; 7Chang Gung Memorial Hospital, Taipei, 7Comprehensive Cancer Center, Fondazione Policlinico Universitario “A. Taiwan Gemelli” IRCCS, Rome, Italy; 8Medical Oncology Division, Ospedale Maggiore Policlinico - Fondazione IRCCS Ca’ Granda, Milan, Italy; Background: In the pivotal OAK study, the 2/3L treatment for advanced 9Dipartimento di Oncologia Clinica, AOU Ospedali Riuniti Ancona, Torrette or metastatic NSCLC with atezolizumab (atezo) resulted in improvement Di Ancona, Italy; 10Dipartimento di Terapie Innovative in Medicina e of OS. Despite its efficacy has been approved, little is known about atezo Odontoiatria, UniversitàG. D’Annunzio Chieti-Pescara, Chieti, Italy; clinical outcomes in routine practice in the Asian population. This study 11Policlinico Universitario Campus Bio-Medico, Rome, Italy; 12Oncology, aimed to understand the clinical characteristics and outcomes of NSCLC Azienda Ospedaliera Universitaria Careggi, Florence, Italy; 13Medical patients treated with atezo in second-line and beyond (2L+) in the real- Oncology, Policlinico Umberto I, Rome, Italy; 14Azienda Sanitaria world setting. Universitaria Integrata di Udine, Udine, Italy; 15Oncology, Azienda Methods: We retrospectively collected patient-level data of atezo-based Ospedaliera S. Camillo Forlanini, Rome, Italy; 16Department of Human treatments in 6 medical centers in Taiwan from 2017 to 2019. Patients Pathology, University of Messina, Messina, Italy; 17Oncology Dept., HUG - demographic, disease characteristics, treatments, outcomes, and adverse Hopitaux Universitaires de Geneve, Geneva, Switzerland; 18Ospedale Civile events of special interest (AESI) were recorded. San Salvatore, L’Aquila, L’Aquila, Italy; 19Universitàdegli Studi dell’Aquila, Results: Among 123 atezo-treated NSCLC patients who had received at L’Aquila, Italy; 20Imperial College London - Hammersmith Hospital, least one prior chemotherapy regimens, broader patient population were London, UK recorded, including those with multiple prior lines of treatments (64% in 2/3L setting and 37% in 4L+) and those with poorer performance Background: Tumors related to inherited susceptibility seem to have an status (18% with ECOG PS ≥2). 76 (61.8%) patients receiving atezo "immune-sensitive phenotype". We previously showed that family monotherapy and 43 (35.0%) patients receiving atezo + chemotherapy. history of cancer (FHC) was associated to clinical benefit from PD-1/ The real-world median PFS and OS for 2L+ patients treated with atezo PD-L1 checkpoint inhibitors in advanced cancer patients. monotherapy were 4.5 months and 11.1 months, respectively. Among Methods: We present the outcomes analysis according to FHC in two atezo-monotherapy treated 2L+ patients with evaluable treatment large multicenter cohorts of metastatic NSCLC patients receiving responses, the ORR and DCR were 8.5% and 45.1%, respectively. Data first-line pembrolizumab (PD-L1 expression ≥ 50%) and first-line from patients receiving atezo+chemotherapy will be reported. For all 2L chemotherapy. FHC was collected in straight and collateral lines, patients + patients, the AESI was occurred in 16 (13.0%) patients. Immune- were categorized FHC-high (in case of at least one cancer diagnosis in related hepatitis (n = 7, 5.7%) was the most common AESI, followed by both straight and collateral family lines) and non-FHC-high. The role of immune-related pneumonitis (n = 3, 2.4%). FHC was validated in pooled multivariable analyses using the Conclusions: This study demonstrated the real-world outcome of therapeutic modality (pembrolizumab vs chemotherapy) as interaction atezolizumab monotherapy in 2L+ NSCLC is consistent with its pivotal term. study. Clinical benefits were observed in NSCLC patients receiving Results: 728 and 652 patients were included in the pembrolizumab and atezolizumab-based treatments per clinical judgment. Enriched benefits chemotherapy cohort, respectively. Within the chemotherapy cohort was observed in certain patient profile and this may inform treatment 48.3% of patients received immunotherapy as later line. In univariate decisions to support better patient outcomes in clinical practice. analysis FHC-high patients achieved longer OS (p = 0.0190) and PFS Legal entity responsible for the study: This study was managed by (p = 0.0041), and higher DCR (88.2% vs 65.6%, p = 0.0009) compared Formosa Biomedical Technology Corp. contract research organization to non-FHC-high. In multivariable analysis FHC-high patients were and overseen by Roche Products Ltd., Taiwan. confirmed to have a significantly higher DCR (OR = 3.43 [95%CI: 1.42– Funding: Roche Products Ltd. 8.31], p = 0.0061) and longer PFS (HR = 0.64 [95%CI: 0.45–0.92], p = Disclosure: S-G. Wu: Honoraria (self ): Roche; Honoraria (self ): AstraZeneca; 0.0167), while only a trend towards a prolonged OS was reported (HR = Honoraria (self ): Pfizer. C-L. Chiang: Honoraria (self ): Roche; Honoraria (self ): 0,69 [95%CI: 0,46–1,04]; p = 0,0780). Among the chemotherapy cohort Boehringer Ingelheim; Honoraria (self ): AstraZeneca. T-C. Hsia: Research grant/ FHC-high patients experienced a significantly longer OS compared to Funding (self ): Eli Lilly. C-Y. Su: Full/Part-time employment: Roche. C-F. Chen: non-FHC-high patients on univariable analysis (p = 0.0307), while no Full/Part-time employment: Roche. J-Y. Shih: Honoraria (self ), Advisory/ Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self ), significant associations were found regarding DCR and PFS. At the Advisory/Consultancy: AstraZeneca; Honoraria (self ), Advisory/Consultancy, pooled analysis, the interaction was not significant with respect to DCR Travel/Accommodation/Expenses: Pfizer; Honoraria (self ), Advisory/ (p = 0.0899) and OS (p = 0.7854), while a significant interaction was Consultancy: Boehringer Ingelheim; Honoraria (self ), Advisory/Consultancy: Eli reported with respect to PFS (p = 0.0197), finally confirming the Lilly; Honoraria (self ), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Honoraria (self ), Advisory/Consultancy: Ono differential impact of FHC between the two cohorts. Pharmaceutical; Honoraria (self ), Advisory/Consultancy, Travel/ Conclusions: FHC-high status identifies NSCLC patients with longer PFS Accommodation/Expenses: Chugai Pharmaceutical; Honoraria (self ), Advisory/ and higher DCR following pembrolizumab but not chemotherapy, Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria suggesting its role as a surrogate marker for immunotherapy. The (self ): Novartis. All other authors have declared no conflicts of interest. bases underlying this phenomenon warrant mechanistic investigation. Legal entity responsible for the study: The authors. S762 Journal of Thoracic Oncology Vol. 16 No. 4S

Funding: Has not received any funding. cut-offs of 18 and 5. Overall survival from start of ICI (OS) was analyzed Disclosure: A. Cortellini: Advisory/Consultancy, Speaker Bureau/Expert testi- with Cox regression models, including cross-validation by calculation of mony: AstraZeneca; Speaker Bureau/Expert testimony: Astellas; Advisory/ the Harrel’s C-index. Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: Roche; Results: High ALI values (>18) were significantly associated with longer Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis. S. Buti: – Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; OS for patients receiving ICI monotherapy (HR = 0.41, 95%CI 0.31 0.54, Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/ p < 0.0001, n = 460), but not chemoimmunotherapy (HR = 0.68, 95%CI Consultancy, Speaker Bureau/Expert testimony: IPSEN; Advisory/Consultancy, 0.4–1.16 with p = 0.16, n = 212). Similar positive correlations with ALI Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker were also observed for the RR (36% vs 24%, p = 0.008) and time-on- Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert – testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ely- treatment (TOT, HR = 0.52, 95% CI: 0.41 0.65, p < 0.001). In the Lilly.Di Maio: Research grant/Funding (self ): Tesaro; Research grant/Funding (self ): chemotherapy cohort the association between ALI and OS was weaker GSK; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/ (HR = 0.69, 95%CI: 0.57–0.84, p = 0.0002), and showed a significant Consultancy: Eisai; Advisory/Consultancy: Takeda; Advisory/Consultancy: Janssen; interaction with the type of treatment (ICI monotherapy vs. chemother- Advisory/Consultancy: Astellas; Advisory/Consultancy: Roche; Advisory/ Consultancy: AstraZeneca. R. Giusti: Advisory/Consultancy, Speaker Bureau/Expert apy, p < 0.0001). The neutrophil-to-lymphocyte ratio (NLR), PD-L1 testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: tumor proportion score (TPS), LIPI and EPSILoN scores were also Roche. E. Bria: Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert associated with clinical benefit in case of ICI monotherapy only, but had testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: weaker effects than ALI. Among patients with PD-L1 TPS ≥50% Pfizer; Speaker Bureau/Expert testimony: Helsinn; Speaker Bureau/Expert testimony: Eli-Lilly; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert receiving first-line ICI monotherapy, mainly pembrolizumab, a high testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: ALI score >18 identified a subset with long OS and TOT (median 35 and Roche. A. Addeo: Advisory/Consultancy: Takeda; Advisory/Consultancy: MSD; 16 months, respectively), at least comparable to those under Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Advisory/ chemoimmunotherapy. Consultancy: Pfizer. D.J. Pinato: Speaker Bureau/Expert testimony: ViiV Healthcare; Speaker Bureau/Expert testimony: Bayer Healthcare; Advisory/Consultancy: Conclusions: ALI score is a powerful prognostic and predictive Mina Therapeutics; Advisory/Consultancy: EISAI; Advisory/Consultancy: Roche; biomarker for patients with advanced NSCLC treated with PD-(L)1 Advisory/Consultancy: AstraZeneca; Research grant/Funding (institution): BMS; inhibitors alone, but not in combination with chemotherapy. For PD-L1- Research grant/Funding (institution): MSD. All other authors have declared no high patients, a high ALI score >18 could assist selection of cases that do conflicts of interest. not need addition of chemotherapy. Prospective validation of ALI is warranted. Legal entity responsible for the study: The authors. 118P Funding: Has not received any funding. The clinical utility of advanced lung inflammation index (ALI) Disclosure: G. Mountzios: Honoraria (self ), Advisory/Consultancy, Speaker for immunotherapy guidance in non-small cell lung cancer Bureau/Expert testimony: Amgen; Honoraria (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Honoraria (self ), Advisory/ 1 2 3 4 5 Consultancy, Speaker Bureau/Expert testimony: BMS; Honoraria (self ), G. Mountzios , E. Samantas , K. Senghas , J. Krisam , S. Angelaki , Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Honoraria 6 7 8 9 G. Pentheroudakis , A. Psyrri , P. Kosmidis , R. Elshafie , (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; H. Linardou10, F. Herth11, M. Meister3, T. Muley3, E. Razis12, Honoraria (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony: A. Stenzinger13, I. Boukovinas14, M. Reck15, K. Syrigos16, Novartis; Honoraria (self ), Advisory/Consultancy: Takeda Hellas; Honoraria 17 17 1 (self ), Advisory/Consultancy: Pfizer; Honoraria (self ), Advisory/Consultancy, M. Thomas , P. Christopoulos Second Department of Medical Speaker Bureau/Expert testimony: Boehringer Ingelheim. E. Samantas: Honoraria Oncology and Clinical TrialsUnit, Henry Dunant Hospital Centre, Athens, (self ), Advisory/Consultancy: Amgen; Honoraria (self ), Advisory/Consultancy: Greece, 2Second Department of Medical Oncology, Metropolitan Hospital, Novartis; Honoraria (self ), Advisory/Consultancy: BMS; Honoraria (self ), Faliro, Attica, Greece; 3Thoraxklinik at Heidelberg University Hospital, Advisory/Consultancy: MSD; Honoraria (self ), Advisory/Consultancy: Roche; 4 Honoraria (self ), Advisory/Consultancy: AstraZeneca Greece; Honoraria (self ): Heidelberg/Germany, Heidelberg, Germany; Institute of Medical Pfizer; Honoraria (self ): Takeda. S. Angelaki: Honoraria (self ), Advisory/ Biometry and Informatics - University Hospital Heidelberg, Heidelberg, Consultancy: Amgen; Honoraria (self ), Advisory/Consultancy: Roche; Honoraria Germany; 5University Hospital of Heraklion (PAGNI), Heraklion, Crete, (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Greece; 6Scientific and Medical Division, ESMO - European Society for Honoraria (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; 7 Honoraria (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Medical Oncology, Lugano, Switzerland; Internal Medicine/Medical Honoraria (self ), Advisory/Consultancy: Novartis; Honoraria (self ), Advisory/ 8 Oncology, Attikon University Hospital, Haidari, Greece; Hygeia Hospital, Consultancy: Takeda Hellas; Honoraria (self ), Advisory/Consultancy: Pfizer. Athens, Greece; 9Radiation Oncology, Heidelberg University Hospital, G. Pentheroudakis: Honoraria (self ), Advisory/Consultancy: Amgen; Honoraria Heidelberg, Germany; 10Oncology Department, Metropolitan Hospital, (self ), Advisory/Consultancy: Sanofi; Honoraria (self ), Advisory/Consultancy: 11 Novartis; Honoraria (self ), Advisory/Consultancy: Roche; Honoraria (self ), Athens, N. Faliro, Greece; Pneumology Department, Thoraxklinik Advisory/Consultancy: BMS; Honoraria (self ), Advisory/Consultancy: 12 Heidelberg, Heidelberg, Germany; Third Department of Medical AstraZeneca Greece; Honoraria (self ): Leo; Honoraria (self ), Advisory/ Oncology, Hygeia Hospital, Marousi, Greece; 13Pathology, Heidelberg Consultancy: MSD; Honoraria (self ): Pierre Fabre; Honoraria (self ): Genesis; University Hospital, Heidelberg, Germany; 14Medical Oncology Unit Honoraria (self ), Advisory/Consultancy: Ipsen. A. Psyrri: Honoraria (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Honoraria Department, Bioclinic Oncology Unit of Thessaloniki, Athens, Greece; (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; 15 Thoracic Oncology Dept., Krankenhaus Grosshansdorf, Grosshansdorf, Honoraria (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony: Germany; 16Third Department of Medicine, University of Athens, Sotiria Merck Serono; Honoraria (self ), Advisory/Consultancy: Roche; Honoraria (self ), General Chest Diseases Hospital, Athens, Greece; 17Oncology Department, Advisory/Consultancy: Pfizer Greece; Honoraria (self ): Ipsen. P. Kosmidis: Honoraria (self ): Amgen; Honoraria (self ): Roche; Honoraria (self ): BMS; Thoraxklinik Heidelberg, Heidelberg, Germany Honoraria (self ): MSD; Honoraria (self ): AstraZeneca; Honoraria (self ): Novartis; Honoraria (self ): Takeda Hellas; Honoraria (self ): Ipsen; Honoraria Background: The advanced lung inflammation index (ALI: body mass (self ): Sanofi. R. Elshafie: Honoraria (self ), Advisory/Consultancy: Accuray; index X serum albumin/neutrophil-to-lymphocyte ratio (NLR)) reflects Honoraria (self ): AstraZeneca; Honoraria (self ): BMS; Honoraria (self ): systemic inflammation, is easily reproducible in clinical practice and Novocure; Honoraria (self ): Merck Serono; Honoraria (self ): Takeda. could assist guidance of non-small cell lung cancer (NSCLC) treatment H. Linardou: Honoraria (self ), Advisory/Consultancy: Amgen; Honoraria (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS Greece; Honoraria with immune checkpoint inhibitors (ICI). (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Honoraria Methods: This retrospective study included an experimental cohort of (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; 672 stage IV NSCLC patients treated with PD(L)1 inhibitors alone or Honoraria (self ), Advisory/Consultancy: Novartis; Honoraria (self ), Advisory/ combined with chemotherapy in 25 centers in Greece and Germany and Consultancy: Takeda; Honoraria (self ), Advisory/Consultancy: Sanofi; Honoraria (self ), Advisory/Consultancy: IPSEN; Honoraria (self ), Advisory/Consultancy, a control cohort of 444 stage IV NSCLC patients treated with platinum- Speaker Bureau/Expert testimony: AstraZeneca. F. Herth: Honoraria (self ), based chemotherapy. ALI and NLR were dichotomized at the published Advisory/Consultancy: Lilly; Honoraria (self ), Advisory/Consultancy: Roche; April 2021 Abstracts S763

Honoraria (self ), Advisory/Consultancy: AstraZeneca; Honoraria (self ), Advisory/ Methods: We retrospectively reviewed clinical data of aNSCLC pts Consultancy: Novartis Hellas; Honoraria (self ), Advisory/Consultancy: consecutively treated with ICIs at Istituto Oncologico Veneto between Boehringer; Honoraria (self ), Advisory/Consultancy: Chiesi; Honoraria (self ), Advisory/Consultancy: Teva; Honoraria (self ), Advisory/Consultancy: Pulmonx; August 2013 and March 2020. We collected data on type, severity (G) Honoraria (self ), Advisory/Consultancy: BTG; Honoraria (self ), Advisory/ and timing of irAEs and calculated neutrophil-to-lymphocyte ratio (NLR) Consultancy: Olympus. T. Muley: Research grant/Funding (self ), Licensing/ and platelet-to-lymphocyte ratio (PLR) before first ICI administration Royalties: Roche. E. Razis: Honoraria (self ): Roche; Honoraria (self ): BMS Greece; and at irAEs onset. The values were dichotomized for analysis in two Honoraria (self ): MSD; Honoraria (self ): AstraZeneca; Honoraria (self ): Pfizer Greece; Honoraria (self ): Novartis. A. Stenzinger: Honoraria (self ): BMS; groups: high (H-) and low (L-) NLR and H- and L-PLR, using pre- Honoraria (self ): AstraZeneca; Honoraria (self ): Thermofisher; Honoraria (self ): identified cut-offs of 3 and 180, respectively. Novartis Hellas; Honoraria (self ), Research grant/Funding (self ): Illumina; Results: Pts included in the analysis were 304. ICIs were administered Honoraria (self ): MSD Hellas; Honoraria (self ): Roche. I. Boukovinas: Honoraria as first-line treatment in 91 (29.9%) pts. Median number of ICIs cycles (self ), Advisory/Consultancy: AstraZeneca; Honoraria (self ), Advisory/ – Consultancy: BMS Greece; Honoraria (self ), Advisory/Consultancy: MSD; was 6 (range 1 66). Median PFS and OS were 5.5 months (m) (95% CI Honoraria (self ), Advisory/Consultancy: Ipsen; Honoraria (self ), Advisory/ 4.2–6.7) and 21.3 m (95% CI 17.2–25.4). 118 pts (38.8%) developed Consultancy: Amgen; Honoraria (self ), Advisory/Consultancy: Sanofi; Honoraria irAEs, mainly G1–2 (85%), with permanent ICI discontinuation in 18 (self ), Speaker Bureau/Expert testimony: Leo; Honoraria (self ): Pierre Fabre; (15.2%) cases; 11 pts (9.3%) experienced more than one irAE. Median Honoraria (self ): Genesis. M. Reck: Honoraria (self ), Advisory/Consultancy: – Amgen; Honoraria (self ), Advisory/Consultancy: Roche; Honoraria (self ), time to irAE onset was 69 days (range 7 664). Pts with baseline L-NLR Advisory/Consultancy: BMS; Honoraria (self ), Advisory/Consultancy: MSD; and L-PLR values had a higher risk of irAE development (OR = 2.52, 95% Honoraria (self ), Advisory/Consultancy: AstraZeneca; Honoraria (self ): Merck CI 1.49–4.23, p < 0.001 and OR = 2.08, 95% CI 1.25–3.47, p = 0.005). Serono; Honoraria (self ): Boehringer Ingelheim; Honoraria (self ), Advisory/ Multivariate analysis confirmed NLR as an independent predictive Consultancy: Lilly; Honoraria (self ): Samsung. K. Syrigos: Honoraria (self ), – Advisory/Consultancy: Roche; Honoraria (self ), Advisory/Consultancy: BMS marker (OR = 1.90, 95% CI 1.07 3.41; p = 0.030). Among pts who Greece; Honoraria (self ), Advisory/Consultancy: AstraZeneca; Honoraria (self ), experienced an irAE, L-PLR at the time of irAE onset was associated with Advisory/Consultancy: MSD. M. Thomas: Honoraria (self ), Advisory/Consultancy: a higher risk of recurrence or development of a different irAE (OR = 3.3, Novartis; Honoraria (self ), Advisory/Consultancy: Lilly; Honoraria (self ), 95% CI 1.18–9.07, p = 0.020). Advisory/Consultancy: BMS; Honoraria (self ), Advisory/Consultancy: MSD; Honoraria (self ): Takeda; Honoraria (self ): Celgene; Honoraria (self ), Advisory/ Conclusions: NLR and PLR evaluation at baseline may be a useful tool Consultancy: AbbVie; Honoraria (self ): Boehringer Ingelheim; Honoraria (self ): to predict the risk of irAE development and might help planning a Pfizer; Honoraria (self ): Samsung. P. Christopoulos: Advisory/Consultancy, tailored follow-up during and after treatment with ICIs. PLR values at Research grant/Funding (self ): AstraZeneca; Honoraria (institution), Research irAE onset may predict the risk of further toxicity. If validated, PLR value grant/Funding (self ): Novartis; Advisory/Consultancy, Research grant/Funding (self ): Roche; Advisory/Consultancy, Research grant/Funding (self ): Takeda; may support the clinical decision of re-introducing ICIs after Honoraria (self ): Boehringer Ingelheim; Advisory/Consultancy: Chugai; discontinuation. Honoraria (self ): Pfizer; Honoraria (self ): MSD. All other authors have declared Legal entity responsible for the study: Istituto Oncologico Veneto – no conflicts of interest. IRCCS. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest. 119P The role of circulating markers in predicting immune-related adverse events (irAEs) and their recurrence in advanced non- 120P small cell lung cancer (aNSCLC) patients (pts) Checkpoint inhibitors in responding patients with advanced carcinoma lung: Can we stop treatment? A single-center 1 2 1 1 3 1 A. Dal Maso , A. Pavan , A. Ferro , G. Pretelli , S. Frega , J. Menis , experience G. Pasello1, V. Guarneri1, P.F. Conte1, L. Bonanno3 1Dipartimento di ̀ Scienze Chirurgiche, Oncologiche e Gastroenterologiche, Universita degli R. Ashwath, A. Rauthan, P. Patil, P. Vundemodalu, N. Yashas, 2 Studi di Padova, Padua, Italy; Oncologia Medica, AULSS 3 Serenissima, G. Nigade Medical Oncology, Manipal Comprehensive Cancer Center 3 Mestre, Italy; Oncologia 2, Istituto Oncologico Veneto IOV - IRCCS, Padua, Manipal Hospital, Bangalore, India Italy Background: Immunotherapy with PD1/ PDL1 checkpoint inhibitors Background: Immune checkpoint inhibitors (ICIs) have radically has become a part of treatment in all advanced stage non-small cell lung changed aNSCLC treatment. However, timely recognition and manage- cancer (NSCLC) patients without a driver mutation, either as a first line ment of irAEs is essential in order to avoid potentially life-threatening or in subsequent lines of treatment. It is approved as monotherapy in events. No markers are available to predict the onset of irAEs and their high PD-L1 expressed patients with a duration of 2 years as evidenced by recurrence risk. Aim of the study was to evaluate the potential role of trials. There is limited data on shorter duration of treatment. So due to circulating markers in predicting the irAE development. logistical issues in our country (India) short course treatment has been used in a few individuals.

Table 120P

Duration Serial of Best response CR- Months of follow up Response duration No of Year of treatment Number Complete response after stopping from partial Current disease/patient patients diagnosis Age/Sex (Months) of cycles PR-Partial response therapy diagnosis (months) status 1 May 2017 65 yrs/M 16 18 CR 24 28 Continues to be in CR 2 Feb 2018 66 yrs/M 14 22 PR 3 29 Continues to be in PR 3 Apr 2018 87 yrs/M 13 22 PR 16 27 Continues to be in PR 4 May 2018 74 yrs/M 12 16 PR 16 26 Continues to be in PR 5 Oct 2018 79 yrs/M 13 21 PR 5 16 Expired due to cardiac disease 6 Dec 2018 72 yrs/M 5 8 PR 17 19 Continues to be in PR 7 Sep 2019 73 yrs/M 8 9 PR 5 11 Continues to be in PR 8 Oct 2019 70 yrs/M 4 5 PR 8 10 Continues to be in PR S764 Journal of Thoracic Oncology Vol. 16 No. 4S

Methods: We did a retrospective analysis of patients who received G12D and 20 (6%) codon 13. 48 patients (12%) demonstrated a mutation checkpoint inhibitors in metastatic NSCLC in various lines at our institute in NF1, of which 20 (42%) harboured a concomitant KRAS mutation. Of from May 2017 to Sep 2020. Out of 70 patients who received checkpoint KRAS patients harbouring a co-mutation with NF1, 9 (45%) had a G12C inhibitors, we had 8 patients who stopped treatment after achieving a mutation vs. 7 (35%) codon 13 mutation. Median overall survival (OS) good response. None of them had EGFR, ALK or ROS1 alterations on following first line therapy for KRAS, NF1 and KRAS-NF1 co-mutant single gene testing. They all had high PDL1 positive status (sp263). All of patients was variable, with the most favourable outcomes occurring in them received nivolumab, between 5 to 22 cycles. Duration of treatment NF1 and KRAS-NF1 patients (19.2 vs. 27.9 vs. 27.9 months; p = 0.34). ranged from 4 monthsto 16 months. All patients were evaluated with PET Conclusions: Results demonstrated that KRAS codon 13 had an CT scan every 3 months after stopping treatment. unexpected bias with NF1 mutations in NSCLC. OS was variable across Results: subgroups, suggesting NF1 co-mutations may signal improved OS Conclusions: In our series of patients, we have seen eight patients who relative to KRAS mutant patients. Ongoing investigation is planned to have stopped treatment afterachieving good response, and continue to do analyse mutations upstream of RAS determining therapeutic response in well on follow up. It would be intriguing to study shorter duration of this subgroup. treatment in responding patients. This would reduce the cost of treatment Legal entity responsible for the study: The authors. and would enable more patients to take up this treatment. Quality of life Funding: Has not received any funding. was better with very minimal symptoms. We would also need to further Disclosure: All authors have declared no conflicts of interest. study biomarkers like PDL1 and beyond to choose this group of responding patients who could receive shorter duration of treatment. Legal entity responsible for the study: The authors. 122P Funding: Has not received any funding. STK11 and/or KEAP1 mutations and outcomes in non-small Disclosure: All authors have declared no conflicts of interest. cell lung cancer patients treated with immune checkpoint inhibitors: A systematic literature review

121P A. Codima1, G. Monteiro1, I. Costa1, D. Kashiura2, L. Torres2, RAS precision medicine trans-atlantic partnership: Multi- G. Julian2, G. Harada3, G.D.C. Junior4 1University of São Paulo - Faculty 2 centre analysis of RAS and NF1 co-mutations in advanced of Medicine, São Paulo, Brazil; IQVIA Real World Insights, São Paulo, 3 ı́ ̃ NSCLC Brazil; Centro de Oncologia, Hospital S rio-Libanês, Sao Paulo, Brazil; 4Medical Oncology, University of São Paulo - Faculty of Medicine, São H. Adderley1, M. Aldea2, J. Aredo3, M. Carter4,5, M. Church1, Paulo, Brazil 4,5 4,5 6 7 8 F. Blackhall , M. Krebs , H. Wakelee , B. Besse , D. Planchard , Background: Immune checkpoint inhibitors (ICIs) have recently 9 10 4,5 1 D. Vasseur , C. Massard , C. Lindsay The Christie NHS Foundation become a major strategy in treatment of non-small cell lung cancer 2 Trust, Manchester, UK; Institute Gustave Roussy, Villejuif, France; (NSCLC), but somatic mutations involving the STK11 and KEAP1 genes 3 Division of Oncology, Department of Medicine, Stanford Cancer Institute, may elicit resistance to anti-PD(L)1 agents. We conducted a systematic 4 Stanford University, Stanford, CA, USA; Division of Cancer Sciences, review aiming to determine if these mutations are significantly related to Faculty of Biology, Medicine and Health, Christie Hospital, University of poorer outcomes in NSCLC patients (pts) treated with ICIs. 5 Manchester, Manchester, UK; Cancer Research UK, Lung Cancer Centre of Methods: PubMed, Web of Science, and EMBASE databases were 6 Excellence, Manchester, UK; Division of Oncology, Department of systematically screened for cohorts carrying STK11 and/or KEAP-1 Medicine, Stanford Cancer Institute, Stanford University, Stanford, CA, mutations, and for subgroup analysis of randomized controlled trials 7 USA; Thoracic Group, Department of Cancer Medicine, Institut Gustave (RCTs) comparing the outcomes of these pts and wild-type carriers. The 8 Roussy, Villejuif, France; Medical Oncology Department, Institut Gustave outcomes of interest were overall survival (OS), progression-free 9 Roussy, Villejuif, France; Department of Molecular Biology, Institute survival (PFS) and response rate (RR). 10 Gustave Roussy, Villejuif, France; Department of Therapeutic Innovation Results: From a total of 3521 records identified, four RCTs and five and Early Trials (DITEP), Institute Gustave Roussy, Villejuif, France cohort studies were included and all but one of them suggest that the STK11 and KEAP1 mutations impair response to anti-PD(L)1 agents. Background: RAS mutations are the most common oncogenic drivers in lung cancer, with KRAS mutated in ∼30% of NSCLC. Renewed optimism Eight studies provided data related to OS, suggesting it is shorter in STK11-mutated pts compared to wild-type carriers (median of 7.9 mo in targeting RAS has been led by the development of direct KRAS G12C – – inhibitors, which bind covalently to the mutant cysteine residue when [4.4 18] vs 15.6 mo [11.3 26.18]). Six studies provided data related to – – KRAS G12C is in the inactive GDP-bound state. NF1 encodes the RAS GAP RR, which was lower in mutated pts (4 31% vs 16 57.1%). Five studies provided median PFS for both groups, which was also lower in mutated neurofibromin, functioning as an inhibitor of the MAPK pathway by – – facilitating transition of RAS to its GDP-bound state. Given new pts (median of 3.2 mo [1.8 6.3] vs 6 mo [2.7 15.2]). The comparison of OS between the KEAP-1-mutated groups and wild-type carriers were knowledge that KRAS G12C is a ‘cycling’ mutant, upstream targetting provided by four studies, which have also shown poorer prognosis of NF1 mutation is of renewed interest for KRAS mutant disease. Through – – collaboration we aim to extend knowledge of RAS and NF1 co-mutation in related to this mutation (9.2 mo [6 17] vs 15.8 mo [8.3 24]). Three studies provided data comparing RR between these groups and have also NSCLC evaluating biological, clinical and treatment effects. – Methods: 413 patients with RAS and or NF1 mutant NSCLC were suggested a poorer response associated to the mutation (16.7 36% vs 23.9–48%). Two studies provided PFS data for both groups, which were retrospectively identified from The Christie NHS Foundation Trust, The found to be of 9 and 6 months for the mutated pts and of 10 and 12 Gustave Roussy Cancer Centre, and Stanford University between Aug 2008 - Dec 2020. DNA from archival FFPE samples, serum orcombination months for the wild-type carriers. Conclusions: Mutations to the STK11 and/or KEAP1 genes apparently underwent targeted NGS to identify mutations. Molecular, clinical, pathological and outcome data was collected and Kaplan-Meier survival elicit resistance to ICIs in NSCLC pts. A meta-analysis is warranted for a complete assessment of this effect, so that clinicians may potentially analysis performed to test for survival differences between subtypes. investigate the presence of these mutations for a better reasoning of Results: 413 patients underwent analysis (mean age 64, range 19-92). 39 patients (9%) had stage IIIb disease with the remainder stage IV. therapy choice. Legal entity responsible for the study: The authors. KRAS mutations were identified in 353 patients (85%), amongst these 144 (41%) harboured a mutation in G12C, 56 (16%) G12 V, 67 (19%) Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest. April 2021 Abstracts S765

and the allelic frequency of mutant KRAS might help to select the best 123P treatment option. Impact of the STK11 mutation on the response to Methods: Patients (Pts) diagnosed with advanced KRAS mt NSCLC immunotherapy determined by ctDNA next-generation sequencing (NGS), tissue NGS or both, were identified in our institutional lung cancer molecular database A. Kalantari1, T. Pieters1, K. Sawadogo2 1Pulmonology, Cliniques between 2011 and 2020. We retrospectively reviewed the response rate Universitaires Saint-Luc (UCLouvain Saint-Luc), Woluwe-Saint-Lambert, (RR) defined by RECIST1.1, with antiPD-1/PD-L1 and the potential Belgium; 2Statistics, Cliniques Universitaires Saint-Luc (UCLouvain Saint- correlation with co-mutations and the assessment of KRAS mutational Luc), Woluwe-Saint-Lambert, Belgium status based on plasma or tissue biopsy. Clinicopathological characteristics were collected. Stata 15.1 was used for the analysis. Background: STK11mutation is present in 20% of bronchial adenocar- Results: 69 pts were identified among 264 KRAS mt NSCLC pts. The cinoma and is associated with the KRAS mutation in 30% and KEAP1 in average age at diagnosis was 62 (39–80) years. 63.7% were male. The 25% of cases. STK11 mutation appears to confer resistance to anti-PD- most common histology was adenocarcinoma (82.61%). Most of patients (L)1. We wanted to analyze the impact of this STK11 mutation on clinical (73.85%) were smokers with more than 30 pack-year (py) and only 3% charactericitcs, overall survival (OS) and progression-free survival (PFS) never smokers. PDL1 was known in 91% of patients (25% <1%, 26% 1– in patients treated with an anti-PD-(L)1 in 1st or 2nd line. 49%, 41% >50%). KRAS mt was determined by NGS in plasma (27.5%), Methods: We conducted a single-center retrospective study of patients tissue (45%), both (18.8%) or other non-NGS techniques (8.7%). 59.4% with stage IV non-small cell lung cancer treated at Cliniques pts had co-mutations (65.8% in plasma), TP53 was the most common Universitaires Saint-Luc between September 2017 and June 2020. We (18/40). KRAS G12C was the most frequent KRAS mutation subtype isolated 3 groups: STK11mut/KRASmut, STK11mut/KRASwt, identified (42.03%). 54.89% pts received IT as 1-line (L) treatment, STK11wt/KRASmut. The clinical characteristics sought were age at 42.03% as 2L and 3.08% as 3L. Pts without co-mutations had diagnosis, sex, smoking status, histology, stage at diagnosis, status KRAS, significantly lower response rate (RR) to IT (21.1% vs 50%, p = STK11, type of treatment in 1st line and second line, PFS and OS. 0.048). Regarding assessment of KRAS mutational status on plasma vs Results: 227 patients with NSCLC had NGS. A total of 95 patients had an tissue biopsy, there were no statistically significant differences in RR STK11 mutation, or KRAS, or both. Of these 95 patients, 44 were (38.7% vs 36.1%, p = 1). Our study was limited by its retrospective included in our study. KRASmut and STK11mut was present respectively design and selection of patients with heterogeneous disease. in 40.91% and 20.45% of our population while the KRAS/STK11 co- Conclusions: Co-mutational status of KRAS could be related to better mutation in 38.64%. PD-L1 expression was predominantly present in response to IT. Further randomized trials are needed to evaluate the role STK11mut patients (n = 26; >1% in 61.54%; >50% in 23.1%). 34 of KRAS co-mutational status and KRAS assessment in plasma or tissue patients were treated with an anti-PD-(L1), 26 in first line including 11 in biopsy and outcomes with IT. combination with chemotherapy and 8 in second line. Taking into Legal entity responsible for the study: The authors. account the mutation status and after treatment with immunotherapy, Funding: Has not received any funding. the shortest OS was observed in the STK11mut/KRASmut population Disclosure: P. Garrido Lopez: Honoraria (self ), Advisory/Consultancy: with an OS of 6.9 months, compared to 8.3 months in the STK11mut AstraZeneca; Honoraria (self ), Advisory/Consultancy: Boehringer Ingelheim; population and 33.9 months in the KRASmut population (CI95: 7.9– Honoraria (self ), Advisory/Consultancy: Bristol (BMS); Honoraria (self ), Advisory/Consultancy: Janssen; Honoraria (self ): Novartis; Honoraria (self ), 33.9/p = 0.018). These results are only significant between the Advisory/Consultancy: Pfizer; Honoraria (self ), Advisory/Consultancy: MSD; KRASmut and KRASmut/STK11mut groups (p = 0.017). PFS was not Honoraria (self ), Advisory/Consultancy: Roche; Honoraria (self ), Advisory/ statistically different between groups. Consultancy: Takeda; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Conclusions: This study corroborates the negative impact on OS of GlaxoSmithKline (GSK); Advisory/Consultancy: Lilly; Advisory/Consultancy: Bayer. All other authors have declared no conflicts of interest. STK11 mutation whether or not associated with a KRAS mutation in patients treated with an anti-PD- (L) 1, despite the high level of PD-L1 expression in our population. We could not assess whether STK11 mutation plays a prognostic or a predictive role. 125P Legal entity responsible for the study: Cliniques Universitaires Saint Benefit of immunotherapy in advanced NSCLC patients Luc. selected by KRAS mutations: A single institute retrospective Funding: Has not received any funding. analysis Disclosure: All authors have declared no conflicts of interest. J.J. Soto Castillo1, E. Corral de la Fuente1, M.E. Olmedo Garcıá1, A. Gómez Rueda1, Y. Lage1, E.M. Vida Navas1, L. Sanz Gómez1, 2 1 1 124P M. Lario , P. Garrido Lopez Medical Oncology Department, Hospital 2 ı́ ́ KRAS mutated (mt) non-small cell lung cancer (NSCLC) and Universitario Ramon y Cajal, Madrid, Spain; Dept. Anatom a Patologica, response to antiPD-1/PD-L1 regarding co-mutational status Hospital Universitario Ramon y Cajal, Madrid, Spain and assessment of KRAS mutation on plasma or tissue biopsy Background: Kirsten Rat Sarcoma (KRAS) viral oncogene is the most common oncogenic driver in non-small cell lung cancer (NSCLC), altered E. Corral de la Fuente1, J.J. Soto Castillo2,A.Gómez Rueda2, Y. Lage2, in around 25–30% adenocarcinomas and present in both localized and M.E. Olmedo Garcıá2, E.M. Vida Navas2, J. Torres Jiménez2, advanced disease. Within KRAS, G12C, G12 V and G12A mutations are P. Álvarez Ballesteros2, M. Lario2, A. Benito Berlinches3, generally related with the smoking habit. Despite being highly prevalent P. Garrido Lopez2 1Department of Oncology, Hospital Universitario aberrations, the predictive and prognostic roles of these molecular Ramon y Cajal, Madrid, Spain; 2Medical Oncology, Hospital Universitario alterations still are investigational in NSCLC patients treated with Ramon y Cajal, Madrid, Spain; 3Dept. Pathology, Hospital Universitario immunotherapy (IT). Ramon y Cajal, Madrid, Spain Methods: We retrospectively assessed the efficacy outcomes (response rates [RR], progression-free survival [PFS]) in KRASm advanced NSCLC Background: Kirsten Rat Sarcoma viral oncogene (KRAS) mt advanced patients who received IT in our institution between 2016 and 2020, NSCLC conforms a heterogeneous disease typically treated with considering correlation with G12C, G12D and G12 V mutations. cytotoxic chemotherapy in combination with immunotherapy (IT) or Histological features and co-occurring mutations (detected by ctDNA IT alone based on PD-L1 expression. Co-mutations, KRAS mt subtypes S766 Journal of Thoracic Oncology Vol. 16 No. 4S next-generation sequencing [NGS], tissue NGS or both) were also was 20.8 months (m, CI95% 17.8–25.3) and median progression-free collected. Stata 15.1 was used for the analysis. survival (PFS) was 4.8 m (CI95% 3.7–6.4) for ICI treatment. Presence of Results: Sixty-nine patients were included. Mean age was 62 (39–80), brain, liver and bone met were statistically significant prognostic factors. men represented 63.7%, heavy smokers were 73.8%, and adenocarcin- Median OS for p with brain met was 7.2 m vs 12 m for pts without CNS oma histology was 82.6%. KRAS G12C was the most common KRAS met, p = 0.021; median OS for pts with liver met was 5.43 m vs 12.4 m, p subtype (41.9%), followed by G12D (19.4%), and G12 V (16.1%). PDL1 < 0.0001; and median OS for pts with bone met was 7.3 m vs 15.6 m, p < status was known in 91% (24.6% <1%, 26% 1–49%, 40.5% >50%). 0.0001. We did not detect significant differences in survival according to Main pathogenic co-mutation identified by NGS were: TP53, CDKN2A, gender or smoking status. Our results indicate that PS, histology and BRCA2, PIK3CA, CDK4/CDK6, and ALK. Variants of Unknown bone met were significant predictive factors. Pts with PS 2 had worse Significance (VUS) were: GNAS, MET, MYC, and SMAD4. At 1st line, survival (median PFS 12.8 m vs 1.9 m for PS 0 and 2, respectively; p = chemo-IT was used in 14 patients (38.8%) and IT alone in 22 (61.2%). At 0.007). Large cell neuroendocrine histology is related with worse PFS 1st line, RR was the same for G12C, G12D, and G12 V (50%). There were (2.7 m vs 5.6 m in adenocarcinoma, p = 0.02; or vs 7.4 m in squamous, p no differences between PFS for KRAS G12C and non-G12C (8.2 vs 9.3 m, = 0.05). Median PFS with ICI in pts with bone met was 3.2 m vs 7.76 m p = 0.66), not for G12D and non-G12D (9.6 vs 8.7 m, p = 0.75), and not without bones met, p = 0.04. for G12 V and non-G12 V (7.1 vs 9.2 m, p = 0.58). At 2nd line, IT alone Conclusions: In our real-world experience, clinical features provide was used in 30 patients (90.1%). In this setting, RR were slightly higher predictive information regarding ICI treatment in NSCLC pts. Clinical for KRAS G12D (50%) than for G12C (25%) and for G12 V (0%), but parameters may help physicians to guide treatment decisions. without significant differences. Median PFS was not statistically superior Incorporation of selective biomarkers needs further investigation. for any KRAS subtype. Legal entity responsible for the study: The authors. Conclusions: Our results suggest that KRAS G12C, G12D or G12 V Funding: Has not received any funding. mutations could not be a good predictive factor for response to Disclosure: A. Callejo: Advisory/Consultancy, Travel/Accommodation/ immunotherapy. This study was limited by its retrospective design and Expenses: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche limited selection of patients. AG; Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD Legal entity responsible for the study: The authors. Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: Grunenthal Funding: Has not received any funding. Pharma. P. Iranzo: Advisory/Consultancy, Travel/Accommodation/Expenses: Disclosure: All authors have declared no conflicts of interest. BMS; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche AG; Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: Grunenthal Pharma. J. 126P D. Assaf: Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD. N. Pardo: Clinical predictive factors in real world setting in advanced Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/ non-small cell lung cancer (NSCLC) patients (pts) treated with Consultancy, Travel/Accommodation/Expenses: Roche AG; Advisory/ Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; immune checkpoint inhibitors (ICI) Advisory/Consultancy, Travel/Accommodation/Expenses: MSD Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer. A. Navarro: A. Callejo1, D. Marmolejo1, P. Iranzo1, J.D. Assaf1, N. Pardo1, Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/ A. Navarro1, A. Martinez-Marti1, S. Cedres2, N.M. Diaz Mejia3, Consultancy, Travel/Accommodation/Expenses: Roche AG; Advisory/ 1 4 5 6 1 Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; C. Carbonell , R. Amat , J. Frigola , E. Felip Medical Oncology Dept., Advisory/Consultancy, Travel/Accommodation/Expenses: MSD Oncology; Vall d’Hebron Institute of Oncology and University Hospital, Barcelona, Advisory/Consultancy, Travel/Accommodation/Expenses: Oryzon Genomics; Spain; 2Medical Oncology Dept., Vall d’Hebron University Hospital, Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer. A. Martinez- Barcelona, Spain; 3Vall d’Hebron University Hospital, Barcelona, Spain; Marti: Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/ Consultancy, Travel/Accommodation/Expenses: Roche AG; Advisory/Consultancy, 4Thoracic Tumors Lab, Vall d’Hebron Institute of Oncology and University 5 Travel/Accommodation/Expenses: Boehringer Ingelheim; Advisory/Consultancy, Hospital, Barcelona, Spain; Thoracic Tumors and Head and Neck Cancer Travel/Accommodation/Expenses: MSD Oncology; Advisory/Consultancy, Travel/ Group, Vall d’Hebron Institute of Oncology (VHIO)-Cellex Center, Accommodation/Expenses: Pfizer. S. Cedres: Advisory/Consultancy, Travel/ Barcelona, Spain; 6Medical Oncology Service (Lung Cancer Unit), Vall Accommodation/Expenses: BMS; Advisory/Consultancy, Travel/ ’ Accommodation/Expenses: MSD; Advisory/Consultancy, Travel/ d Hebron University Hospital, Barcelona, Spain Accommodation/Expenses: Boehringer Ingelheim; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche AG; Advisory/Consultancy, Travel/ Background: ICI have significantly changed the therapeutic landscape Accommodation/Expenses: Pfizer; Advisory/Consultancy: Amphera. N.M. Diaz of advanced NSCLC. Biomarkers to select patients who benefit most from Mejia: Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/ immunotherapy remains unclear. We investigated the role of gender, Consultancy, Travel/Accommodation/Expenses: MSD. E. Felip: Advisory/ smoking history, histology, performance status (PS) and metastases Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche AG; Advisory/Consultancy, Speaker (met) localization as clinical predictive factors to ICI in a real-world Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker cohort of pts. Bureau/Expert testimony: MSD Oncology; Advisory/Consultancy, Speaker Methods: 263 pts treated with ICI at Vall d’Hebron University Hospital Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/ between 2013 and 2019 were studied. Associations between clinico- Expert testimony: AbbVie; Advisory/Consultancy, Speaker Bureau/Expert testimony: Blueprint; Advisory/Consultancy, Speaker Bureau/Expert testimony: pathological features and outcomes were assessed with Cox regression Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; models and survival data were calculated by the Kaplan-Meier method. Advisory/Consultancy, Speaker Bureau/Expert testimony: Guardant Health; Results: 182 pts were male (69.2%). 205 (78%) had non-squamous Advisory/Consultancy, Speaker Bureau/Expert testimony: Medscape; Advisory/ histology among which 6 (2.2%) were large cell neuroendocrine. Before Consultancy, Speaker Bureau/Expert testimony: Touchtime; Advisory/ Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, starting ICI, 53 pts had PS0 (20.1%) and 19 PS2 (7.2%). Baseline brain Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy, Speaker met were diagnosed in 59 pts (22.8%) and 86.4% of them have been Bureau/Expert testimony: Celgene; Advisory/Consultancy: Merck sharp; treated with radiotherapy, 63 pts had liver met (23.9%) and 94 pts had Research grant/Funding (self ), Research grant/Funding (institution): EMD bones met (35.7%). In the total population, median overall survival (OS) Serono Oncology. All other authors have declared no conflicts of interest. April 2021 Abstracts S767

Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD Oncology; Advisory/Consultancy, Travel/ 127P Accommodation/Expenses: Boehringer Ingelheim; Advisory/Consultancy, Travel/ Real-world evidence and clinical characteristics in patients Accommodation/Expenses: F Hoffmann La Roche; Advisory/Consultancy, Travel/ (pts) with advanced non-small cell lung cancer (NSCLC) Accommodation/Expenses: Pfizer; Advisory/Consultancy: Oryzon Genomics. A. Martinez-Marti: Advisory/Consultancy, Travel/Accommodation/Expenses: treated with immune checkpoint inhibitors (ICI) Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: P. Iranzo1, A. Callejo1, D. Marmolejo1, J.D. Assaf1, N. Pardo1, F. Hoffmann La Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy, A. Navarro1, A. Martinez-Marti1, S. Cedres1, N.M. Diaz Mejia2, Travel/Accommodation/Expenses: Boehringer. S. Cedres: Advisory/Consultancy, 1 3 4 1 1 Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, C. Carbonell , R. Amat , J. Frigola , E. Felip Medical Oncology Dept., Travel/Accommodation/Expenses: MSD Oncology; Advisory/Consultancy, Travel/ Vall d’Hebron Institute of Oncology and University Hospital, Barcelona, Accommodation/Expenses: Boehringer Ingelheim; Advisory/Consultancy, Travel/ Spain; 2Vall d’Hebron University Hospital, Barcelona, Spain; 3Thoracic Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/ Tumors Lab, Vall d’Hebron Institute of Oncology and University Hospital, Accommodation/Expenses: Amphera; Advisory/Consultancy, Travel/ 4 Accommodation/Expenses: F. Hoffmann La Roche. N.M. Diaz Mejia: Advisory/ Barcelona, Spain; Thoracic Tumors and Head and Neck Cancer Group, Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/ Vall d’Hebron Institute of Oncology (VHIO)-Cellex Center, Barcelona, Spain Consultancy, Travel/Accommodation/Expenses: MSD Oncology. E. Felip: Advisory/Consultancy, Speaker Bureau/Expert testimony: AbbVie; Advisory/ Background: Advanced NSCLC treatment has been improved by the Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/ emergence of ICI. Only around 20% of unselected patients exhibit a Consultancy, Speaker Bureau/Expert testimony: Blueprint medicines; Advisory/ positive response to this type of treatment. Great efforts to identify Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/ Consultancy, Speaker Bureau/Expert testimony: MSD Oncology; Advisory/ different factors that can potentially guide clinicians to predict response Consultancy, Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy, to ICI are being made. We investigated the role of clinical factors such as Speaker Bureau/Expert testimony: F. Hoffmann La Roche; Advisory/Consultancy, PD-L1 expression, age, EGFR mutation(mut) and concomitant medica- Speaker Bureau/Expert testimony: Janssen; Advisory/Consultancy, Speaker tions (statins, oral antidiabetic drugs and betablockers) in a real-world Bureau/Expert testimony: Merck KGaA; Advisory/Consultancy, Speaker Bureau/ Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert cohort of pts. testimony: Touchtime; Advisory/Consultancy, Speaker Bureau/Expert testimony: Methods: Real life data were obtained from 263 consecutive pts with Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Celgene; advanced NSCLC treated with ICI at Vall d’Hebron University Hospital Advisory/Consultancy, Speaker Bureau/Expert testimony: Medscape; Advisory/ between 2013 and 2019 were studied. Patient data were obtained Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/ Consultancy, Speaker Bureau/Expert testimony: Guardant Health; Advisory/ retrospectively. Progression-free survival (PFS) was calculated using the Consultancy, Speaker Bureau/Expert testimony: Pfizer; Research grant/Funding Kaplan-Meier estimates and cox regression analysis was performed for (self ), Research grant/Funding (institution): EMD Serono Oncology Innovation. All factors potentially influencing survival. other authors have declared no conflicts of interest. Results: Median age for pts at diagnosis was 62.3 years (range 33–87). 182 (69.2%) were male; 165 (62.7%) were former smokers and 68 (25.9%) current smokers. Non-squamous was the most common 128P histology (78%). An EGFR mutation was identified in 13 pts (4.94%). A real-world scenario of applicability of immuno oncology At the time of starting treatment with ICI, 86 pts (32.7%) received agents into practice in NSCLC in a resource constrained concomitant statins, 40 (15.2%) oral antidiabetic drugs (OADs) and 35 setting (13.3%) beta-blockers. Median OS for all pts was 20.8 months (m, CI95% 17.8–25.3) and median PFS was 4.8 m (CI95% 3.7–6.4) for ICI G. Sharat Chandra, M. Singhal, A. Sharma, S. Valame, D. Panda treatment. The median PFS by age group were: 4.9 m in pts younger Medical Oncology Department-J 70, Pocket J, Indraprastha Apollo than 55 years (y); 6.6 m in those with age 55 to 75 y and 5.6 m in older Hospital, New Delhi, India than 75y (p = 0.69, age >75 y vs 55–75 y) (p = 0.96; >75 y vs 55–75 y). Median PFS was 1.8 m for EGFR mut pts and 6.1 m for EGFR wild type (p Background: Non-small cell lung cancer is one cancer which has seen = 0.02). Median PFS in pts with PD-L1 positive tumours was 11.7 m vs radical change in treatment in the last decade with the advent of 5.3 m in PD-L1 negative (p = 0.1). Regarding concomitant medications, immunotherapy and targeted therapies. Chemo immunotherapy has the results showed that statins, OADs and beta-blockers have no increased the survival multi fold in metastatic setting and also in earlier significant effect on PFS. Median PFS for patients receiving statins, OADs lines and is the first line treatment now in non driver mutation setting. and beta-blockers were 7 m (p = 0.49); 8.5 m (p = 0.51) and 3.8 m (p = However, applicability of the same into real world practice has been 0.38) respectively. dismal in low and middle income countries due to various reasons. Data Conclusions: These real-world data provide useful information for is lacking in this setting. clinicians helping to identify factors which can be helpful to predict Methods: We conducted a prospective observational study to see the tumour response and potential benefit of ICI therapy. applicability of Immuno Oncology drug indications in stage 3 and 4 Legal entity responsible for the study: The authors. NSCLC patients. Consecutive patients between March 2018 and Funding: Has not received any funding. February 2020 who had an approved indication for IO regimen usage Disclosure: P. Iranzo: Advisory/Consultancy, Travel/Accommodation/ were included. Stage 3b and 3c and stage 4 driver mutation negative Expenses: Bristol-Myers Squibb; Advisory/Consultancy: F. Hofmann La Roche; patients were taken into the study. Their treatment regimens were Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; studied and reasons for non usage of IO regimen were assessed. Advisory/Consultancy, Travel/Accommodation/Expenses: MSD Oncology; Results: Between March 2018 and February 2020, 88 patients were Advisory/Consultancy: Grunenthal. A. Callejo: Advisory/Consultancy, Travel/ enrolled who were eligible for treatment with IO agents in NSCLC. Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Travel/ Among them, stage 3b were 9%, stage 3c were 11.3% and stage 4 were Accommodation/Expenses: F. Hoffmann La Roche; Advisory/Consultancy, Travel/ Accommodation/Expenses: MSD Oncology; Advisory/Consultancy, Travel/ 79.7% patients. Only 30 patients (34%) could receive IO agents in their Accommodation/Expenses: Boehringer; Advisory/Consultancy: Grunenthal treatment regimen across various lines of therapy. In stage 4 Pharma. J.D. Assaf: Advisory/Consultancy, Travel/Accommodation/Expenses: NSCLC,35.7% patients were treated with IO agents either in the 1st Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: line or later lines. In stage 3, 5 of 18 patients went on to receive IO agent MSD Oncology. N. Pardo: Advisory/Consultancy, Travel/Accommodation/ Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/ post definitive chemo radiation. The most common reason for non usage Expenses: MSD Oncology; Advisory/Consultancy, Travel/Accommodation/ of IO agents were financial constraints (68.9%) including exhaustion of Expenses: Boehringer Ingelheim; Advisory/Consultancy, Travel/ insurance limit, denial by insurance company (20.6%) and non Accommodation/Expenses: F Hoffmann La Roche; Advisory/Consultancy, availability of drug (10.5%). Of 30 patients who received IO agents, 8 Travel/Accommodation/Expenses: Pfizer. A. Navarro: Advisory/Consultancy, S768 Journal of Thoracic Oncology Vol. 16 No. 4S patients had to withdraw owing to financial toxicity while they were still responding with average time to withdrawal being 7.2 months. 130P Conclusions: This observational study depicts the real world scenario of Neutrophil-to-lymphocyte ratio as a response predictor to the difficulties in bringing approved regimen into practice with financial immune checkpoint inhibitors in non-small cell lung cancer toxicity being the reason the non usage in nearly 60% patients. In low income countries, this needs to be addressed if more number of patients C. Amorim Costa, M.R. Pires, J.C. Monteiro, A.C. Caetano, are to be benefitted from IO agents in NSCLC. F.R. Salgueiro, J. Correia Magalhães, M.J.P. de Sousa, R. Basto, Legal entity responsible for the study: The authors. A.R. Meira Garcia, I. Domingues, E. Jesus, G. Sousa Medical Oncology Funding: Has not received any funding. Department, Instituto Portugues Oncologia de Coimbra Francisco Gentil Disclosure: All authors have declared no conflicts of interest. E. P. E. (IPO Coimbra), Coimbra, Portugal Background: The immune checkpoint inhibitors (ICIs) have changed 129P the treatment of non-small cell lung cancer (NSCLC) but there are few Predicting response to immunotherapy in advanced non-small predictive and prognostic biomarkers. Even with high levels of PD-L1 cell lung cancer expression, some patients do not benefit from anti-PD1 or PD-L1 inhibitors. Neutrophil-to-lymphocyte ratio (NLR) has been shown to be a M. Rebordão Pires, C. Amorim Costa, T. Cunha Pereira, J.C. Monteiro, potential biomarker in these settings. I. Domingues, A.C. Caetano, A.R. Meira Garcia, E. Jesus, G. Sousa Methods: The primary endpoint was to evaluate NLR relation with Medical Oncology Department, Portuguese Institute for Oncology of progression-free survival (PFS) and overall survival (OS). Secondary Coimbra, Coimbra, Portugal endpoints were analysis of population demographics and major toxicities to ICIs. Unicentric, retrospective clinical study, including all Background: The advanced Non-Small Cell Lung Cancer’s (aNSCLC) patients with advanced NSCLC treated with ICIs. NLR is calculated by response to immunotherapy (IO) is heterogenous, thus biomarkers to dividing the absolute neutrophil count by the absolute lymphocyte count predict response are needed. EPSILoN and NLCIPS (Non-Small Cell Lung from a complete blood count with differential. NLR was defined as high Cancer Immunotherapy Prognosis Score) are two predictive models when > 2,375 and low when ≤ 2,375, using ROC curve. PFS was which help to identify aNSCLC patients who will benefit from IO. calculated by the Kaplan-Meier method. Methods: We conducted a retrospective, single-center study of aNSCLC Results: Sixty-nine patients treated with ICIs from January 2016 until patients who had received IO, between January 2016 and December October 2020 were analysed, with median age of 63 years old, 66.7% 2020. The primary endpoint was progression-free survival (PFS) and its were males, 33.3% non-smokers, 62.3% had an ECOG PS 0, and 58% had correlation with each score. EPSILoN combines five baseline clinical/ stage IV at diagnosis. Thirty-two (46.4%) patients were receiving ICIs as blood parameters: ECOG/PS, smoking, liver metastases, LDH and second line treatment. Thirty-three patients (47.8) received pembroli- neutrophil-to-lymphocyte ratio (NLR). EPSILoN stratified patients in zumab, thirty-two (46.4%) nivolumab and four (5.8%) atezolizumab. good, intermediate or poor responders to IO. NLCIPS is a response The median number of treatments of ICIs were 9 (1–105). Median PFS predictive model based in smoking index and NLR, which stratifies was 7 months (3.0–10.9), with no significative statistical differences patients in 4 groups on 1-year-PFS: very poor, poor, intermediate and between the high and low NLR groups. Median PFS of patients treated good. Descriptive statistical analysis, survival analyses with Kaplan- with nivolumab was 3 months (1.9–4.1), with pembrolizumab was 15 Meier curves and multivariate analyses with cox regression model were months (4.7–25.3) and with atezolizumab was 3 months. made using SPSS®. Immunomediated adverse events (AEs) G3/4 were present in 6 patients Results: We analyzed 70 patients, 68,6% male, median age 62,5 years and required ICIs suspension in all cases. One toxic death with (38–81 years), 57,1% smokers, 57,1% stage IV and 27% expressed PD- pembrolizumab (1 cycle) was observed after hepatic failure. L1³50%. Using EPSILoN score patients were stratified in good 25,7%; Conclusions: Our results were probably due to small population in this intermediate 67,14%; and poor 7,1%. Using NLCIPS predictive model study and it is crucial to search for biomarkers to predict ICIs response. patients were stratified in 4 groups according to predicted 1-year-PFS: These biomarkers will help to define which patients will benefit the most very poor (1-year PFS <0,1) in 18,57%; poor (1-year PFS 0,18) in from these therapeutics. 27,14%; intermediate (1-year PFS 0,28) in 25,7%; and good (1-year PFS Legal entity responsible for the study: The authors. >0,6) in 28,6%. The median follow-up was 8,5 months. Median PFS was Funding: Has not received any funding. 4 months (0–56 months), with statistical significance differences in PFS Disclosure: All authors have declared no conflicts of interest. between groups either applying EPSILoN (p = 0,003) or NLCIPS score (p = 0,008). The multivariate analysis with cox regression, showed a statistically significant difference in PFS using EPSILON score (HR 3,05 131P – – [CI 95% 1,24 7,46], p = 0,015), NLCIPS (HR 0,595 [CI 95% 0,4 0,89], Predictive factors of response to PD-(L)1 inhibitors in patients p = 0,010) and PD-L1³50% (HR 0,247 [CI 95% 0,09–0,68], p = 0,007). with advanced non-small cell lung (NSCLC) and high PD-L1 Conclusions: Our study shows that stratifying aNSCLC patients using either EPSILON or NLCIPS score can help to identify who will most likely expression benefit from IO. Further studies are warranted. A. Barba Joaquıń1, A. Piedra1, J. Mosquera2, M. Riudavets1, Legal entity responsible for the study: Portuguese Institute for 2 3 1 Oncology of Coimbra. M.I. Gomez-Randulfe , M.R. Garcia Campelo , I.G. Sullivan , J. Serra1, M. Aguado1, M. Majem Tarruella1 1Dept. Medical Oncology, Funding: Has not received any funding. 2 Disclosure: All authors have declared no conflicts of interest. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Dept. Medical Oncology, Hospital Universitario a Coruña, A Coruña, Spain; 3Dept. Medical Oncology, Instituto de Investigacioń Biomedicá de A Coruña (INIBIC), A Coruña, Spain Background: Tumor PD-L1 expression is the only biomarker predictive of responsiveness in advanced NSCLC treated with PD-(L)1 inhibitors. Analysis of PD-L1 expression by IHC has been validated in histological samples. Smoking and overweight have been described as predictive April 2021 Abstracts S769 factors of better outcome, whereas bone metastases,antibiotic, corticos- (CT) is a viable option for fit patients, while single-agent CT is an teroids and proton pump inhibitors as predictive factors of poor alternative for selected patients, and immunotherapy and targeted outcome. The aim of our study was to analyze potential predictive therapy are recommended when indicated. However, the elderly are a factors of response to PD-(L)1 inhibitors in patients (pts) with advanced complex and heterogeneous population, that remain a challenge for NSCLC and high PD-L1 expression. oncologists in the real world. Methods: The study was carried out in pts with advanced NSCLC and Methods: We conducted a retrospective study to compare younger (<70 high PD-L1 expression treated with PD-(L)1 inhibitors. Clinical and years) and older (≥70 years) patients with stage IV Non-Small Cell Lung histological variables of interest were registered. Kaplan-Meier estima- Cancer (NSCLC), regarding treatment choices and overall survival (OS), tions were used to calculate survival, and log-rank test to make being these two the primary endpoints. The secondary endpoints were comparisons. The impact of variables on survival was assessed through to describe and compare the two groups, to assess which characteristics univariate and multivariate analysis. We present preliminary results of were associated with poor prognosis, and to evaluate the occurrence of the analysis. grade 3–4 toxicities. Results: 86 pts were included in the analysis. Mean age was 66 y [36– Results: We included 118 patients with a newly diagnosed stage IV 84], 21 (24.4%) were females, 73.3% former smokers and 22.1% NSCLC discussed and oriented in a Multidisciplinary Meeting at our current smokers, 38,4% presented normal BMI, 79% had non-squamous institution between January of 2017 and December of 2019, divided into NSCLC, 85% received PD-(L)1 inhibitors in first line and 12% pts had group A (<70 years) (n = 70) and group B (≥70 years) (n = 48). There cytological sample for PD-L1 determination. 72 (84%) pts received was a statistically significant difference regarding the the Eastern monotherapy with PD-(L)1 inhibitor, 4 (5%) pts CT plus PD-(L)1 Cooperative Oncology Group Performance Status (ECOG PS) (p = 0.005) inhibitor and 10 (11.6%) pts received PD-(L)1 inhibitors with other and molecular target (p = 0.04), with group B having higher ECOG PS immunotherapy. The mean OS and PFS were 14.1 and 9.6 months, values and higher prevalence of EGFR mutation over ALK. Factors such respectively. ORR and DCR in overall patients were 57% and 72.7%, as having brain (HR: 2.172; 95% IC: 1.209–3.905; p = 0.01) or bone (HR: respectively and ORR and DCR in pts treated in first line were 57.6% and 1.856; 95% IC: 1.060–3.251; p = 0.03) metastasis or not undergoing 73.4%, respectively. Better results were detected in overweight and in systemic treatment (HR: 9.191; 95% IC: 4.496–18.788; p < 0,001) smoker pts despite not being estatistically significant. A trend to worse showed negative influence on OS. Only 63,6% (n = 75) of the patients OS was observed in pts with bone metastasis. No differences in OS were underwent systemic treatment. In these patients there was a difference observed according to the type of tumor sample (cytological and regarding the chosen 1st line treatment (p = 0.02), with a higher histological samples). prevalence of the platinum-based doublet CT in the group Avs B (61% vs Conclusions: Preliminary results showed that smoking and overweight 42%), at the expense of a lower prevalence of single-agent CT (8% vs could be potential predictive factors of better outcome withe bone 27%, respectively). There were no significant differences concerning OS metastasis potential predictive factors of poor outcome, and no differences or incidence of grade 3–4 toxicities. in survival were observed according to the type of tumor sample. Conclusions: Age should not be a decisive factor for the realization of Legal entity responsible for the study: The authors. systemic treatment. A personalized and appropriate choice of treatment Funding: Has not received any funding. can improve compliance and tolerance, without detriment to survival. Disclosure: A. Barba Joaquın:́ Advisory/Consultancy, Speaker Bureau/Expert Legal entity responsible for the study: The authors. testimony: Roche; Travel/Accommodation/Expenses: Merk; Speaker Bureau/ Funding: Has not received any funding. Expert testimony: Bristol; Speaker Bureau/Expert testimony: Angelini. Disclosure: All authors have declared no conflicts of interest. M. Riudavets: Travel/Accommodation/Expenses: Roche; Travel/ Accommodation/Expenses: Merk. M.R. Garcia Campelo: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/ Accommodation/Expenses: Merk; Speaker Bureau/Expert testimony, Travel/ 133P Accommodation/Expenses: Pfizer; Speaker Bureau/Expert testimony: Drug-drug interactions (DDIs) in non-small cell lung cancer Boehringer; Speaker Bureau/Expert testimony: AstraZeneca. I.G. Sullivan: during chemotherapy-immunotherapy treatment Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/ Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony, Travel/ 1 1 1 1 1 Accommodation/Expenses: Merk; Travel/Accommodation/Expenses: Pfizer; M. Occhipinti , M. Brambilla , G. Galli , S. Manglaviti , A. Prelaj , Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Speaker R. Ferrara1, A. De Toma1, T. Beninato1, E. Zattarin1, C. Proto1, Bureau/Expert testimony: AstraZeneca. M. Majem Tarruella: Advisory/ G. Lo Russo1, A.J. Gelibter2, M. Simmaco3, M.C. Garassino1, Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/ 2 1 Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, P. Marchetti Medical Oncology Department, Fondazione IRCCS Istituto 2 Travel/Accommodation/Expenses: BMS; Speaker Bureau/Expert testimony: Nazionale dei Tumori, Milan, Italy; Medical Oncology Unit B, Policlinico AstraZeneca; Speaker Bureau/Expert testimony: Boehringer; Speaker Bureau/ Umberto I - Sapienza University of Rome, Rome, Italy; 3Laboratory of Expert testimony: Novartis; Speaker Bureau/Expert testimony: Pfizer. All other Clinical Biochemistry - Advanced Molecular Diagnostic Unit, Sant’Andrea authors have declared no conflicts of interest. University Hospital, Rome, Italy Background: Polypharmacotherapy is a relevant issue in cancer patients, 132P since the onset of a drug-drug Interaction (DDI) may affect both treatment Stage IV non-small cell lung cancer in the elderly: Real-world efficacy and toxicity. Immune checkpoint inhibitors (ICIs) have rekindled data the interest in DDIs beyond pharmacodynamic and pharmacokinetic considerations. Concomitant drugs (CDs), such as steroids, proton pump J.C. Monteiro1, C. Amorim Costa2, M. Rebordão Pires1, A.C. Caetano2, inhibitors and antibiotics can influence the clinical efficacyof ICIs. Herewe 1 1 3 1 present the use of Drug-PIN® (Personalized Interactions Network) F.R. Salgueiro , I. Domingues , A.R. Meira Garcia , E. Jesus , N.A. Bonito2, G. Sousa1 1Departamento de Oncologia Medica,́ Instituto software in non-small cell lung cancer (NSCLC) patients undergoing chemo-immunotherapy (CHT - ICI). Drug-PIN® is the first intelligent Portugues Oncologia de Coimbra Francisco Gentil E. P. E. (IPO Coimbra), Coimbra, Portugal; 2Medical Oncology Department, Portuguese Institute system that recognizes the critical role of multiple interactions between for Oncology of Coimbra, Coimbra, Portugal; 3Medical Oncology active and/or pro-drug forms by integrating biochemical, demographic, and genomic data of 110 SNPs from each patient. Department, Medical Oncology, Negreiros E Chavão, Portugal Methods: From January 2020 to September 2020 we enrolled patients Background: Lung cancer is commonly diagnosed at an advanced stage with (1) Stage IV NSCLC candidate to receive CHT - ICI (platinum salts - and older age, therefore an increasing number of elderly patients are pemetrexed - pembrolizumab); (2) ECOG PS 0–2; (3) taking at least 1 being considered for systemic treatment. Platinum-based chemotherapy concomitant drug; Toxicities were graded according to CTCAE v5.0. S770 Journal of Thoracic Oncology Vol. 16 No. 4S

Oncologic treatments, CDs, clinical and laboratory data were collected and inserted in Drug-PIN ®. 135P Results: Forty-two patients, with a median age of 63 years (range 35– The real-world use of tyrosine kinase inhibitors (TKIs) in 82) and with a male/female ratio of 22/20, were included. Eight epidermal growth factor receptor mutated (EGFRm) clinically relevant DDIs with a need for medical intervention in a total of advanced (stage IIIb/IIIc/IV) non-small cell lung cancer 6 patients (14%) were identified; the 3 major DDIs were related to a (NSCLC) patients medium grade interaction between pemetrexed and NSAIDs. Thirty-five patients showed at least one toxicity of any grade, of which 15 with grade J. Subramanian1, Y-L. Choi2, T-Y. Chou3,J.Gregg4, R. Hui5, N. Leighl6, ≥ 3. Nineteen patients showed at least one immune related adverse A. Marchetti7, N. Navani8, T. Bailey9, M. Silvey9, R. Makin9, event. We identified a statistically significant association between the D.A. Kahangire10, M. Chau11, A. Taylor10, F. Griesinger12 1Saint use of antiaggregant/anticoagulants (p = 0.01 odds ratio 5.52, 95% CI Luke’s Cancer Institute, Kansas City, MO, USA; 2Samsung Medical Center, 1.23–30.66) and opioids (p = 0.02 odds ratio 5.43, 95% CI 1.1–37.23) Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; and non-response to treatment. 3Taipei Veterans General Hospital, Taipei, Taiwan; 4University of Conclusions: This is the first retrospective study assessing the California, Davis, CA, USA; 5Westmead Hospital and the University of prevalence of DDIs, the clinical need for medical intervention and the Sydney, Sydney, Australia; 6Princess Margaret Cancer Centre, Toronto, ON, impact of concomitant drugs on CHT - ICI efficacy in NSCLC patients. Canada; 7Laboratory of Diagnostic Molecular Oncology, Center for Drug-PIN® could be useful in the era of personalized medicine to Advanced Studies and Technology (CAST), University of Chieti, Chieti, Italy; prevent severe adverse events and improve survival in cancer patients. 8University College London, London, UK; 9Adelphi Real World, Bollington, Legal entity responsible for the study: The authors. UK; 10Global Medical Evidence Generation, AstraZeneca, Cambridge, UK; Funding: Has not received any funding. 11Oncology Business Unit, AstraZeneca, Gaithersburg, MD, USA; 12Pius- Disclosure: G. Lo Russo: Honoraria (institution): Lilly; Honoraria (institution): BMS; Honoraria (institution): AstraZeneca. M.C. Garassino: Honoraria (institution): Hospital Medical Campus, University of Oldenburg, Oldenburg, Germany AstraZeneca; Honoraria (institution): Lilly; Honoraria (institution): Pfizer; Honoraria (institution): BMS; Honoraria (institution): MSD. All other authors Background: Given the role of EGFRm in the development of NSCLC, have declared no conflicts of interest. EGFR is an established target for treating the disease. While EGFR-TKIs are the recommended first-line (1L) treatment option for advanced EGFRm NSCLC, there is limited evidence describing the use of EGFR-TKIs 134P in clinical practice. This study investigated the real-world treatment Effectiveness of immune checkpoint inhibitor monotherapy patterns in advanced EGFRm NSCLC patients. Methods: A physician survey and retrospective medical chart review for postoperative recurrent lung cancer in clinical practice conducted in Australia, Canada, Germany, Italy, South Korea, Taiwan, UK and USA (May – Aug 2020) included 223 physicians and provided data T. Sasaki1, N. Yoshimura2 1Thoracic Surgery, Tohoku Medical and on 1,793 advanced NSCLC patients who received a positive first EGFR Pharmaceutical University, Sendai, Japan; 2Tohoku Medical & test result between Jan – Dec 2017, with data on patient demographics, Pharmaceutical University Komatsushima Campus, Sendai, Japan clinical characteristics, and testing and treatment patterns abstracted Background: There are few clinical trials and literature reports from diagnosis until Mar 2020 (or death). investigating the effects of immune checkpoint inhibitors (ICIs) Results: Median age at advanced diagnosis was 65 years, 54% were specialized in the treatment of postoperative recurrent lung cancer.To male; 17% had a family history of lung cancer. 56% of patients were investigate the specific efficacy of ICI monotherapy in postoperative either smokers or ex-smokers (median pack years: 35); 31% had never recurrent lung cancer. smoked. 84% had advanced NSCLC at presentation. 39% received ≥ 1 Methods: We retrospectively studied the treatment results of 82 cases of treatment prior to EGFRm result, with 14% receiving an EGFR TKI pre postoperative recurrent lung cancer (non-small cell lung cancer) who EGFRm result. Following receipt of EGFRm test result 88% of patients received ICI monotherapy in our department. We extracted factors that initiated ≥ 1 treatment line; 67% of sample initiated EGFR TKIs as 1L contribute to response and survival and examine the efficacy and safety “post EGFRm result” treatment (52–86% between countries); 73% of three types of ICI for postoperative recurrent lung cancer. received an EGFR-TKI “pre” or 1L “post” EGFRm result. 56% of patients Results: I. Nivolumab (n = 37) has a 3-year survival rate of 26% and a received a 1L “post EGFRm result” EGFR TKI alone; 9% received in disease control rate of 61%, which is comparable to clinical trials for combination with chemotherapy. 80% of patients overall received an advanced/recurrent lung cancer, and is particularly good for the elderly EGFR TKI at any line, pre or post confirmation of EGFRm status (range and patients with poor performance status. It seemed to be adaptive. II. 73–94% between countries). Pembrolizumab (n = 29) had a 2-year survival rate of 71%, a response Conclusions: Just under three quarters of patients received an EGFR-TKI rate of 34%, and a disease control rate of 66%, which were as good as either prior to EGFRm test result, or in the 1L “post EGFRm result” those in clinical trials. III. Atezolizumab (n = 16) had a particularly low setting, indicating that while the majority of patients received targeted response rate with a 1-year survival rate of 85%, a response rate of 19%, therapy, over a quarter of patients with confirmed EGFRm status may and a disease control rate of 56%. The prognosis of the driver gene have received sub-optimal treatment. The geographical variations in 1L mutation case was significantly poor (p = 0.01). In the overall EGFR-TKI use observed between countries suggests variability in the multivariate analysis, gene mutation-positive cases had a significantly adoption and implementation of optimal testing and treatment in this poor prognosis (p = 0.02, HR = 0.34). population. Conclusions: The anti-PD-1 antibody drug performed better than the Editorial acknowledgement: Medical writing support under the anti-PD-L1 antibody drug. In addition, the effectiveness of ICI guidance of the authors was provided by Gary Sidgwick of Adelphi administration for postoperative recurrent lung cancer could be shown Real World, on behalf of Adelphi Real World and AstraZeneca, and was as a feature of this study. The number of cases and analysis data will be funded by AstraZeneca in accordance with Good Publication Practice updated and reported at the meeting. (GPP3) guidelines. Legal entity responsible for the study: Ethics Committee of Tohoku Legal entity responsible for the study: AstraZeneca. Medical and Pharmaceutical University Hospital. Funding: AstraZeneca. Funding: Has not received any funding. Disclosure: J. Subramanian: Honoraria (self ), Advisory/Consultancy: AstraZeneca; Honoraria (self ), Advisory/Consultancy: Boehringer-Ingelheim; Disclosure: All authors have declared no conflicts of interest. Advisory/Consultancy: Pfizer; Advisory/Consultancy: Ely Lilly; Advisory/ Consultancy: Novartis; Advisory/Consultancy: Cardinal Health. Y-L. Choi: April 2021 Abstracts S771

Research grant/Funding (institution): AstraZeneca. J. Gregg: Shareholder/ Legal entity responsible for the study: The authors. Stockholder/Stock options, Full/Part-time employment: Freenome; Speaker Funding: Has not received any funding. Bureau/Expert testimony: AstraZeneca. R. Hui: Honoraria (self ), Advisory/ ̈ Consultancy: AstraZeneca; Honoraria (self ), Advisory/Consultancy: Bristol Disclosure: J. von der Thusen: Advisory/Consultancy, Research grant/Funding Myers Squibb; Honoraria (self ), Advisory/Consultancy: Ely Lilly; Honoraria (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (insti- (self ), Advisory/Consultancy: Merck Sharp and Dohme; Honoraria (self ), tution): BMS; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy, Speaker Advisory/Consultancy: Novartis; Honoraria (self ), Advisory/Consultancy: Pfizer; Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert Honoraria (self ), Advisory/Consultancy: Roche; Honoraria (self ), Advisory/ testimony: Roche; Speaker Bureau/Expert testimony, Research grant/Funding Consultancy: Seagen. N. Leighl: Research grant/Funding (institution), Travel/ (institution): Roche Diagnostics. E.J. Dubbink: Honoraria (self ), Advisory/ Accommodation/Expenses: AstraZeneca. N. Navani: Honoraria (self ): BMS; Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/ Honoraria (self ): Pfizer; Honoraria (self ): Takeda; Honoraria (self ), Advisory/ Consultancy: AbbVie; Advisory/Consultancy: Janssen; Honoraria (self ), Consultancy: AstraZeneca; Advisory/Consultancy: Amgen; Advisory/Consultancy: Advisory/Consultancy: Lilly; Honoraria (self ), Advisory/Consultancy: Pfizer; Olympus. D.A. Kahangire: Full/Part-time employment: AstraZeneca. M. Chau: Advisory/Consultancy: PGDx. T. Van Wezel: Research grant/Funding (institution), Shareholder/Stockholder/Stock options, Full/Part-time employment: Research grant was not for this study: ArcherDX. K. Monkhorst: Honoraria (self ), AstraZeneca; Shareholder/Stockholder/Stock options: Roche. A. Taylor: Advisory/Consultancy, Research grant/Funding (institution), Speakers fee: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca; Honoraria (self ), Advisory/Consultancy, Non-remunerated activity/ AstraZeneca. F. Griesinger: Advisory/Consultancy: Roche; Advisory/Consultancy: ies, Speakers fee: Roche; Honoraria (self ), Advisory/Consultancy, Speakers fee: Boehringer-Ingelheim; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/ MSD; Honoraria (self ), Speakers fee: Benecke; Advisory/Consultancy, Non- Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: remunerated activity/ies: Pfizer; Advisory/Consultancy: BMS; Advisory/ Novartis; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Takeda; Consultancy: AbbVie; Advisory/Consultancy: Diaceutics; Advisory/Consultancy: Advisory/Consultancy: Merck Sharp & Dohme. All other authors have declared Lilly; Advisory/Consultancy: Bayer; Advisory/Consultancy: Boehringer Ingelheim; no conflicts of interest. Non-remunerated activity/ies: Takeda; Non-remunerated activity/ies: PGDx; Non- remunerated activity/ies: Delfi. All other authors have declared no conflicts of interest.

136P Best practice recommendations for molecular analysis of 137P acquired EGFR TKI resistance mechanisms Epidermal growth factor receptor mutation status and response to tyrosine kinase inhibitors in advanced Chinese 1 1 ̈ 2 2 L. Hondelink , D. Cohen , J. von der Thusen , E.J. Dubbink , female lung squamous cell carcinoma: A retrospective study T. Van Wezel1, K. Monkhorst3 1Pathology, Leiden University Medical Center, Leiden, Netherlands; 2Erasmus Medical Center, Rotterdam, Q. Chang1, H. Qiang2, C. Tianqing3 1Shanghai Chest Hospital Affiliated Netherlands; 3Pathology, NKI-AVL - Netherlands Cancer Institute/Antoni to Shanghai Jiao Tong University, Shanghai, China, 2Shanghai Jiaotong van Leeuwenhoek Hospital, Amsterdam, Netherlands University, China, China, 3Pulmonary Department, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China Background: With the approval of first line osimertinib treatment in stage IV EGFR mutated NSCLC, detection of potentially targetable Background: The frequency of epidermal growth factor receptor resistance mechanisms will become increasingly important - and (EGFR) mutations and the efficacy of tyrosine kinase inhibitor (TKI) in complex. Clear guidelines on how to test effectively for the wide Chinese female patients with lung squamous cell carcinoma (SCC) are variety of molecular alterations that occur after EGFR-TKI resistance are unknown. This study was designed to investigate the incidence of EGFR currently lacking. Between pathology labs worldwide there is consid- mutations and the role of targeted therapy in advanced Chinese female erable divergence with respect to work-up strategies for resistance lung SCC patients. mechanism detection, potentially leading to incomplete analyses in Methods: Advanced female patients diagnosed with lung SCC at the which treatable targets can be missed. By retrospectively analyzing the Shanghai Chest Hospital between January 2013 and December 2018 yield of different testing modalities in 323 cases from three tertiary were retrospectively analyzed. referral hospitals in the Netherlands, we provide ‘best practice’ Results: A total of 4223 advanced lung SCC patients were screened, and recommendations for optimal molecular diagnostics in the post-EGFR there were 154 female lung SCC patients who had underwent EGFR TKI resistance setting. mutation detection. Positive EGFR mutations were found in 29.9% (46/ Methods: Molecular work-up strategies were compared in 162 first and 154) of female lung SCC patients, including twenty-three 19del mutation second generation TKI treated cases (early-TKI group) and 161 (14.9%), twenty-one 21L858R mutation (13.6%) and other mutations osimertinib treated cases (osimertinib group). Laboratories made use (1.4%, 21861Q and 20ins). For 45 EGFR positive mutation female SCC of combinations of DNA-NGS, RNA-NGS, ISH and immunohistochemical patients, the median progression-free survival (PFS) of patients who techniques. In total, a resistance mechanism was identified in 72 early- received EGFR-TKI therapy (n = 38) was 8.0 months (95% CI, 5.4–10.7 TKI cases (50%) versus 78 osimertinib cases (52%). months), which was significantly longer than patients who were treated Results: RNA-NGS revealed relevant extra information in 4% of early- with chemotherapy (8.0 vs 3.2 months, p = 0.024), and the median TKI cases and 10% of osimertinib cases. Co-occurrence of fusions and overall survival (OS) was also longer (24.9 months vs 13.9 months, p = exon skipping events with any other resistance mechanism detected by 0.020). The objective response rate (ORR) was 44.7% (17/38), and the DNA-NGS or ISH occurred in four out of eight cases (50%). disease control rate (DCR) was 81.6% (31/38). For 105 female SCC Amplifications in HER2 and MET were detected in 12 (12%) of early- patients with EGFR negative mutation, the median OS was 18.6 months TKI cases and 23 (17%) of osimertinib cases. MET- and HER2 ISH (95% CI, 14.2–22.9 months) and it was no different from that of EGFR revealed relevant extra information in 14 cases. In 11 cases (31% of all positive mutation patients (18.6 vs 22.8 months, p = 0.377). MET and HER2 amplifications), the amplification was exclusively Conclusions: For advanced Chinese female lung SCC patients with EGFR detected in ISH or IHC, but was missed in DNA-NGS, especially in positive mutations, targeted therapy could confer longer PFS and OS cases with low tumor-cell percentage. than chemotherapy, but the survival was similar with patients who were Conclusions: Our data support a ‘best practice’ method for molecular negative EGFR mutations. diagnostics in the current practice EGFR TKI resistance setting that Legal entity responsible for the study: The authors. includes DNA-NGS, RNA-NGS, MET ISH and either HER2 ISH or IHC. As Funding: The Western Medicine Guide Project of the Shanghai resistance mechanisms co-occur and fusions and exon-skipping are not Committee of Science and Technology. mutually exclusive events, we advise against using a sequential or more Disclosure: All authors have declared no conflicts of interest. selective approach. S772 Journal of Thoracic Oncology Vol. 16 No. 4S

138P 139P The impact of variant allele frequency in EGFR mutated The impact of TP53 mutations on EGFR mt+ NSCLC IV patients NSCLC patients on targeted therapy treated with 3rd generation TKI on 2nd line or further line therapy: Real-world data from two certified lung cancer A. Addeo1, A. Friedlaender2, M. Chevallier2, C. De Vito2, centers in Germany P. Tsantoulis2 1Oncology Dept., HUG - Hopitaux Universitaires de Geneve, Geneva, Switzerland; 2Hopitaux Universitaires de Geneve - HUG, Geneva, J. Roeper1, P. Christopoulos2, M. Falk3, L.C. Heukamp3, Switzerland A. Stenzinger4, M. Thomas5, F. Griesinger1 1Pius Hospital Oldenburg, Background: Allelic frequency, or the variant EGFR allele frequency, University of Oldenburg, Oldenburg, Germany; 2Oncology Dept., corresponds to the fraction of sequencing reads harbouring the Thoraxklinik Heidelberg, Heidelberg, Germany; 3Hematopathology mutation. The allelic fraction is influenced by the proportion of Hamburg, Hamburg, Germany; 4Pathology, Heidelberg University tumour cells in the sample, the presence of copy number alterations Hospital, Heidelberg, Germany; 5Oncology Dept., Thoraxklinik Heidelberg but also, most importantly, by the proportion of cells within the tumour and Translational Research Center Heidelberg, Member of the German that carry the mutation. Mutations that occur early in tumour evolution, Center for Lung Research (DZL), Heidelberg, Germany often called clonal or truncal, have a higher allelic frequency than late, subclonal mutations, and are more often drivers of cancer evolution and Background: TP53 co-mutations are frequent in EGFR mt+ NSCLC and attractive therapeutic targets. Most, but not all, EGFR mutations are have a strong negative impact on all clinical endpoints in 1st and 2nd clonal. We hypothesized that tumours with low allelic frequency of the generation TKI therapy. However, it is unclear, whether TP53 mutations EGFR mutation will respond less favourably to targeted treatment. also have an impact on the effectiveness of 3rd generation TKI. Methods: We identified all patients treated with front-line TKIs Therefore, we retrospectively analyzed the impact of TP53 co-mutations (gefitinib, erlotinib, afatinib, osimertinib) in our centre for advanced on PFS and OS in a cohort of EGFR mt+ NSCLC IV patients (UICC 7/8) EGFR mutated NSCLC between January 2016 and January 2020. We who developed T790M resistance to 1st and 2nd generation TKI and identified 42 patients. OS was primary endpoint and PFS secondary. were treated with 3rd generation TKI in 2nd or further line. Patient characteristics included sex, age at diagnosis, smoking status, Methods: 77 EGFR mt+ NSCLC IV patients tested for TP53 co-mutations performance status (PS) and presence of brain metastases at diagnosis. and showing a T790M resistance mechanism against 1st or 2nd rd Results: The median allelic frequency of the EGFR mutation was 0.47. generation TKI were treated with 3 generation TKI (Osimertinib) in nd We used a simple cut-off of 0.30 to separate low from high allelic 2 or further lines. The endpoints PFS and OS were investigated in the nd frequency, as a surrogate marker of early, clonal mutations versus late, TP53mt+ vs. TP53WT groups for only 2 line (24 TP53 mt+ vs. 27 TP nd subclonal mutations. High EGFR mutation allelic frequency was WT) and for the complete population (2 and further line). associated with longer PFS (HR 0.27, 95% 0.09–0.79, P = 0.017). igh Results: Baseline characteristics of the 77 EGFR mt+ NSCLC IV patients: allelic frequency was not associated with significant difference in OS (HR median age was 64 years (28–92 years), 65% were female (n = 50/77), 0.47, 95% 0.17–1.30, P = 0.14), Sensitive tumours were associated with 71.4% were never/light smoker (n = 55/77) and 9% had an ECOG of 0 or significantly longer PFS (HR 0.22, 95% 0.07–0.61, P = 0.004) and OS (HR 1 (n = 70/77). 32/77 (42%) had a TP53 mutation, 45/77 (58.4%) were 0.35, 95% 0.13–0.90, P = 0.029). 1yOS was 10% in the insensitive group, TP53 WT. Median PFS of 3rd generation TKI in 2nd line was 9 (n = 24) vs. compared with 79% in the sensitive group. Patients with insensitive 13 months (n = 27) for TP53 mt+ vs. WT (HR 0.499; p < 0.042). Median rd tumours were almost 10 times more likely to die before 12 months than PFS of 3 generation TKI in 2nd and further lines was 9 (n = 32) vs. 14 (n patients with sensitive tumours (Fisher’s test OR 9.7, P = 0.007). = 45) months for TP53 mt+ vs. WT (HR 0.502; p < 0.012). Median OS of rd Conclusions: The mutant allelic frequency of EGFR in NSCLC appears to 3 generation TKI in 2nd and further lines was 16 vs. 24 months for be associated with clinical outcomes among patients treated with TKIs. TP53mt+ (n = 32) vs. WT (n = 45) (HR 0.561; p < 0.031). By combining the latter with variant allelic frequency, we identify two Conclusions: TP53 co-mutations have a negative impact on PFS and OS rd clear prognostic groups, resistant and sensitive patients to TKIs. in EGFR mt+ NSCLC IV patients treated with 3 generation TKI Legal entity responsible for the study: The authors. (Osimertinib) in 2nd line and 2nd/further lines. Thus, p53 is a negative Funding: Has not received any funding. predictor in EGFR mt+ NSCLC patients treated with Osimertinib. TP53 Disclosure: A. Addeo: Honoraria (self ): BMS; Honoraria (self ): Merck; might be an important target to drug in EGFR mt+ NSCLC in combination Honoraria (self ): Astellas; Honoraria (self ): Pfizer; Honoraria (self ): Roche; with Osimertinib. Honoraria (self ): AstraZeneca. A. Friedlaender: Honoraria (self ): BMS; Honoraria Legal entity responsible for the study: University Hospital Internal (self ): Merck; Honoraria (self ): Astellas. All other authors have declared no Medicine-Oncology, Pius Hospital Oldenburg, University Oldenburg. conflicts of interest. Funding: Has not received any funding. Disclosure: J. Roeper: Honoraria (self ): Boehringer Ingelheim; Honoraria (self ): AstraZeneca; Honoraria (self ): Roche. P. Christopoulos: Advisory/Consultancy, Research grant/Funding (self ): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self ): Novartis; Advisory/Consultancy, Research grant/Funding (self ): Roche; Advisory/Consultancy, Research grant/Funding (self ): Takeda; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Chugai; Advisory/Consultancy: Pfizer. M. Falk: Honoraria (self ), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self ): AstraZeneca; Honoraria (self ): Roche; Advisory/Consultancy: Pfizer. L.C. Heukamp: Honoraria (self ), Advisory/ Consultancy: Boehringer Ingelheim; Honoraria (self ), Advisory/Consultancy: AstraZeneca; Honoraria (self ), Advisory/Consultancy: Roche; Honoraria (self ), Advisory/Consultancy: Pfizer; Honoraria (self ), Advisory/Consultancy: Novartis; Honoraria (self ), Advisory/Consultancy: MSD; Honoraria (self ), Advisory/ Consultancy: BMS; Honoraria (self ), Advisory/Consultancy: Siemens. M. Thomas: Honoraria (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self ), Advisory/Consultancy, Research grant/Funding (self ), Travel/ Accommodation/Expenses: Novartis; Honoraria (self ), Advisory/Consultancy: Takeda; Honoraria (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Honoraria (self ), Advisory/Consultancy, Research grant/Funding (self ), Travel/Accommodation/Expenses: MSD; Honoraria (self ), Advisory/ Consultancy, Research grant/Funding (self ), Travel/Accommodation/Expenses: April 2021 Abstracts S773

BMS; Honoraria (self ), Advisory/Consultancy, Research grant/Funding (self ): Conclusions: We did not demonstrate any significant impact of co- Celgene; Honoraria (self ), Advisory/Consultancy: AbbVie; Honoraria (self ), occurring mutations neither on objective response nor on survival in Advisory/Consultancy, Research grant/Funding (self ): Roche. F. Griesinger: Honoraria (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony, EGFR+ advanced NSCLC treated with TKIs. Co-mutations have higher Research grant/Funding (institution), Travel/Accommodation/Expenses: prevalence in young patients and exon 19 mutated tumors. The growing Boehringer Ingelheim; Honoraria (self ), Advisory/Consultancy, Speaker Bureau/ molecular knowledge has to couple with a careful identification of Expert testimony, Research grant/Funding (institution), Travel/Accommodation/ predictive features in order to lead to a risk-based treatment Expenses: AstraZeneca; Honoraria (self ), Advisory/Consultancy, Speaker Bureau/ Expert testimony, Research grant/Funding (institution), Travel/Accommodation/ personalization. Expenses: Roche; Honoraria (self ), Advisory/Consultancy, Speaker Bureau/Expert Legal entity responsible for the study: The authors. testimony, Research grant/Funding (institution), Travel/Accommodation/ Funding: Has not received any funding. Expenses: Pfizer; Honoraria (self ), Advisory/Consultancy, Speaker Bureau/ Disclosure: M.L. Reale: Advisory/Consultancy: Eli Lilly. P. Bironzo: Advisory/ Expert testimony, Research grant/Funding (institution), Travel/Accommodation/ Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: Expenses: Novartis; Honoraria (self ), Advisory/Consultancy, Speaker Bureau/ AstraZeneca; Advisory/Consultancy: BeiGene; Advisory/Consultancy: Roche. Expert testimony, Research grant/Funding (institution), Travel/Accommodation/ M. Di Maio: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer; Expenses: MSD; Honoraria (self ), Advisory/Consultancy, Speaker Bureau/Expert Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/ testimony, Research grant/Funding (institution), Travel/Accommodation/ Consultancy: Takeda; Advisory/Consultancy: Eisai; Advisory/Consultancy: Expenses: BMS; Honoraria (self ), Advisory/Consultancy, Speaker Bureau/Expert Janssen; Advisory/Consultancy: Astellas; Research grant/Funding (institution): testimony, Research grant/Funding (institution), Travel/Accommodation/ Tesaro – GlaxoSmithKline. S. Novello: Speaker Bureau/Expert testimony: Eli Lilly; Expenses: Siemens; Honoraria (self ), Advisory/Consultancy, Speaker Bureau/ Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: Expert testimony, Research grant/Funding (institution), Travel/Accommodation/ Roche; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testi- Expenses: Celgene; Honoraria (self ), Advisory/Consultancy, Speaker Bureau/ mony: Takeda; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert Expert testimony, Research grant/Funding (institution), Travel/Accommodation/ testimony: AstraZeneca; Speaker Bureau/Expert testimony: Boehringer Ingelheim. Expenses: Lilly; Honoraria (self ), Advisory/Consultancy, Speaker Bureau/Expert All other authors have declared no conflicts of interest. testimony, Research grant/Funding (institution), Travel/Accommodation/ Expenses: Takeda; Honoraria (self ), Advisory/Consultancy, Speaker Bureau/ Expert testimony, Research grant/Funding (institution): AbbVie. All other authors have declared no conflicts of interest. 141P Chemotherapy with or without immunotherapy or bevacizumab for EGFR-mutated lung cancer after progression 140P on osimertinib Prognostic and predictive value of co-mutational profile in advanced EGFR positive NSCLC patients treated with TKIs M. White1, J.W. Neal1, R.M. Gardner2, K.M. Cunanan2, M. Das1, S.K. Padda1, K. Ramchandran1, T.T. Chen3, H. Wakelee1 1Stanford 1 1 1 1 1 2 M.L. Reale , P. Bironzo , L. Righi , A. Listi , F. Tabbò, A. Caglio , Comprehensive Cancer Institute, Palo Alto, CA, USA; 2Quantitative Sciences 1 1 2 1 1 C. Pisano , V.M. Napoli , M. Di Maio , S. Novello Department of Unit, Stanford University School of Medicine, Stanford, CA, USA; 3Stanford Oncology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Cancer Center South Bay, San Jose, CA, USA Italy; 2Department of Oncology, University of Turin, Ordine Mauriziano Hospital, Turin, Italy Background: Patients (pts) with advanced EGFR+ lung cancer commonly receive platinum doublet chemotherapy (chemo) regimens Background: EGFR mutations represent the main model of precision after progression on osimertinib (osi), but whether adding immuno- medicine in thoracic oncology. However, an intra-driver diversity exists, therapy (IO) or an anti-angiogenic agent to chemo adds clinical benefit to explaining heterogeneous clinical behavior and treatment responses. this group of pts is not well established. Methods: We retrospectively analyzed the association between con- Methods: Pts with advanced EGFR+ lung cancer who had been on osi comitant mutations and outcome of all advanced EGFR+ NSCLC patients and went on to receive next-line platinum doublet chemo ± IO ± anti- treated with tyrosine kinase inhibitors (TKIs) at our Institutions over the angiogenic agent before July 6, 2020 were retrospectively identified at last 5 years. We performed next-generation targeted sequencing (Ion our university-affiliated cancer center. Pt demographics, treatment Torrent) using a 22 genes clinical panel on diagnostic specimens to history, and outcomes including time on treatment (TOT) and overall analyze the prevalence of co-occurring mutations. survival (OS) from the start of chemo were collected by chart review. We Results: 102 patients were evaluated (64% female, 58% never-smokers, performed log rank tests to compare difference in TOT and OS 99% adenocarcinoma). Exon 19 deletion, exon 21 L858R, uncommon/ distributions between treatment groups. double EGFR mutations were present in 62%, 31%, 7%, respectively. Co- Results: 75 pts were included: 29 received chemo alone, 12 received mutations occurred in 57 patients (56%), most on TP53 (37, 36%). chemo + IO (pembrolizumab in all cases), and 34 received chemo + anti- EGFR exon 19 deletion was associated with a higher incidence of angiogenic agent (bevacizumab (bev) in all cases); no pts received concomitant mutations (39/64, 60.9%) than exon 21 L858R mutation chemo with both IO + bev. Median TOT was 3.9 mo (95% CI 1.9–7.8) for (40.6%, 13/32). Co-mutations had a significantly higher prevalence in chemo alone, 5.2 mo (95% CI 2.5 – Not Estimable) for chemo + IO, and younger patients (p = 0.002). RR for patients with and without co- 5.8 mo (4.5 – NE) for chemo + bev; p = 0.17 for between-group mutations was 63.2% and 51.1% (p = 0.221), respectively. mPFS were differences. Median OS from start of chemo was 12.8 mo (95% CI 6.9– 9.93 and 9.64 months in patients with and without co-mutations (HR 19.5) for chemo, 10.9 mo (95% CI 9.4 – NE) for chemo + IO, and 12.1 mo 0.93, 95% CI 0.59–1.47, p = 0.759), while mOS was 28.7 and 20.8 (95% CI 10.2 – NE) for chemo + bev; p = 0.29 for between-group months (HR 0.74, 95% CI 0.71–1.34, p = 0.319), respectively, with no differences. There were also no differences in TOT or OS in pairwise significant differences according to presence of co-mutations also within comparisons between the 3 treatment groups. treatment subgroups (old vs 3rd generation TKIs). Tumors without co- mutations preferentially progressed to bone and lymph nodes (p = 0.006 and p = 0.027, respectively) with a similar prevalence of T790M resistance mutation at progression (p = 0.72). S774 Journal of Thoracic Oncology Vol. 16 No. 4S

Table 141P: Baseline characteristics by subgroup Myers Squibb; Research grant/Funding (institution): Celgene; Research grant/ Funding (institution): Clovis Oncology; Research grant/Funding (institution): Chemo + IO Chemo + Bev Exelixis; Research grant/Funding (institution): Genentech/Roche; Research grant/ Characteristic Chemo (n = 29) (n = 12) (n = 34) Funding (institution): Gilead; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Merck; Research grant/Funding (institu- Median age, years 63.9 (55.3–72.6) 57.3 (53.4–61.3) 60.9 (53.2–70.5) tion): Novartis; Research grant/Funding (institution): Pfizer; Research grant/ (IQR) Funding (institution): Pharmacyclics; Advisory/Consultancy, Research grant/ Male sex – n (%) 12 (42) 6 (50) 10 (29) Funding (institution): Xcovery; Advisory/Consultancy: Janssen; Advisory/ Race – n (%) Consultancy: Mirati; Advisory/Consultancy: Daiichi Sankyo; Advisory/ Asian 14 (48) 6 (50) 20 (59) Consultancy: Helsinn; Advisory/Consultancy: Blueprint; Honoraria (self ): Clinical Care Options Oncology LLC; Honoraria (self ): Fishawack Facilitate LTD; White 11 (38) 4 (33) 10 (29) Honoraria (self ): Medscape; Honoraria (self ): Onclive/Intellisphere LLC; Other 4 (14) 2 (17) 4 (12) Honoraria (self ): Physicians Education Resource LLC; Honoraria (self ): Prime – ECOG PS n (%) Oncology LLC; Honoraria (self ): Research to Practice; Honoraria (self ): UpToDate; 0–1 19 (65) 11/11 (100) 29 (85) Honoraria (self ): WebMD Health. All other authors have declared no conflicts of 2–3 10 (34) 0 5 (15) interest. EGFR mutation – n (%) Exon 19 deletion 14 (48) 7 (58) 15 (44) L858R 14 (48) 5 (42) 18 (53) Other 1 (3) 0 1 (3) 142P Received osimertinib in 12 (41) 7 (58) 13 (38) EGFR-TKI plus radiotherapy versus EGFR-TKI only in non-small 1st line (vs other EGFR cell lung cancer patients with brain metastasis: A systematic TKIs followed by osi at review and meta-analysis of observational studies progression)

CNS metastases prior 21 (72) 6 (50) 19 (56) 1 1 1 2 to start of chemo – n A. Tancherla , F. Wijovi , T.I. Hariyanto , A. Kurniawan , 3 1 (%) A. Giselvania Faculty of Medicine, Pelita Harapan University, 2 Liver metastases prior 9 (31) 5 (42) 6 (18) Tangerang, Indonesia; Department of Internal Medicine, Pelita Harapan to start of chemo – n University, Tangerang, Indonesia; 3Department of Radiation Oncology, Dr. (%) Cipto Mangunkusumo Hospital-Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

Conclusions: After osi therapy, the addition of IO or bev to chemo in pts Background: Lung cancer accounts for 25% of all cancer deaths, and with EGFR+ lung cancer did not significantly improve clinical outcomes 84% are non-small cell lung cancer (NSCLC). The incidence of brain compared with chemo alone in this cohort. Thus, chemo alone seems a metastasis (BM) was common in NSCLC patients with Epidermal Growth reasonable choice for these pts. Future research could examine larger Factor Receptor (EGFR) mutations, reaching a rate of 63%. Some studies cohorts and adjust for baseline clinical factors. We also await results have reported the effectiveness of treatment with EGFR-tyrosine kinase from ongoing clinical trials examining combinations of chemo ± IO ± inhibitors (TKIs) plus cranial radiotherapy (RT) in NSCLC patients with bev. BM. However, the data available were not consistent. Therefore, we aim Legal entity responsible for the study: The authors. to analyse the prognosis and outcome between TKI plus RT versus TKI Funding: Has not received any funding. only in NSCLC patients with BM. Disclosure: J.W. Neal: Honoraria (self ): Research To Practice; Honoraria (self ): Methods: Data were searched from different databases available online MLI Peerview; Honoraria (self ): Medscape; Honoraria (self ): Biomedical Learning (PubMed, PMC, and Science Direct), using combinations of keywords Institute; Honoraria (self ): Prime Oncology; Honoraria (self ): Rockpointe; related to NSCLC patients with BM, RT, and TKI. The included studies Honoraria (self ): CME Matters; Honoraria (self ): MJH CME; Advisory/ Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (insti- evaluated RT and TKI therapy and their association with the survival and tution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (insti- response rate in NSCLC patients with BM. Quality of each included study tution): Exelixis; Advisory/Consultancy: Jounce Therapeutics; Advisory/ was assessed using the Newcastle-Ottawa Scale (NOS). Consultancy, Research grant/Funding (institution): Takeda Pharmaceuticals; Results: A total of 15 cohort studies were included, which consists of Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy: Calithera Biosciences; Advisory/Consultancy: Amgen; Advisory/Consultancy: Iovance five good quality studies and ten moderate quality studies based on NOS. Biotherapeutics; Research grant/Funding (institution): Merck; Research grant/ Pooled analysis of the studies had indicated that TKI plus RT was not Funding (institution): Novartis; Research grant/Funding (institution): Boehringer significantly associated with overall survival (OS), intracranial progres- Ingelheim; Research grant/Funding (institution): Nektar Therapeutics; Research sion free survival (PFS), and extracranial PFS (p = 0.22, p = 0.20, and p = grant/Funding (institution): Adaptimmune; Research grant/Funding (institution): GlaxoSmithKline; Honoraria (self ): UpToDate. R.M. Gardner: Shareholder/ 0.79 respectively). However, the pooled analysis showed that TKI alone Stockholder/Stock options: Pfizer. M. Das: Research grant/Funding (institution): had resulted in superior response rate (RR) when compared with TKI Novartis; Research grant/Funding (institution): AbbVie; Research grant/Funding plus RT groups (OR = 1.73, 95% CI; 1.23–2.42; p = 0.002). (institution): United Therapeutics; Research grant/Funding (institution): Verily; Conclusions: Qualitative and quantitative analysis showed that TKI plus Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Varian; Honoraria (self ), Advisory/Consultancy: Jazz Pharmaceuticals; RT did not improve the survival of NSCLC patients with BM. This might Honoraria (self ), Advisory/Consultancy: AstraZeneca. S.K. Padda: Research grant/ be due to the observational study design of the included studies which Funding (institution): Epicentrx; Research grant/Funding (institution): Bayer; may cause bias and confounding factors. In addition, our study showed Research grant/Funding (institution): Boehringer Ingelheim; Advisory/ that TKI alone resulted in superior RR in comparison with TKI plus RT Consultancy: Blueprint; Advisory/Consultancy: AstraZeneca; Advisory/ Consultancy: G1 Therapeutic; Honoraria (self ): CME solutions; Advisory/ group. Further randomized clinical trials are needed to evaluate whether Consultancy: Pfizer; Honoraria (self ): PER; Research grant/Funding (institution): the number and size of BM, timing of RT, and different TKI regimens may 47 Inc.; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Janssen pharma- affect the outcome of the patients. ceuticals; Advisory/Consultancy: Clovis Oncology. K. Ramchandran: Advisory/ Legal entity responsible for the study: The authors. Consultancy: Dhristi Inc; Advisory/Consultancy: Varian. H. Wakelee: Research grant/Funding (institution): ACEA Biosciences; Research grant/Funding (institu- Funding: Has not received any funding. tion): Arrys Therapeutics; Advisory/Consultancy, Research grant/Funding (insti- Disclosure: All authors have declared no conflicts of interest. tution): AstraZeneca/Medimmune; Research grant/Funding (institution): Bristol April 2021 Abstracts S775

Speaker Bureau/Expert testimony: AstraZeneca. R. Hui: Honoraria (self ), Advisory/Consultancy: AstraZeneca; Honoraria (self ), Advisory/Consultancy: 143P Bristol Myers Squibb; Honoraria (self ), Advisory/Consultancy: Ely Lilly; Physician perceptions of barriers to epidermal growth factor Honoraria (self ), Advisory/Consultancy: Merck Sharp and Dohme; Honoraria receptor mutation (EGFRm) testing in advanced (stage IIIb/ (self ), Advisory/Consultancy: Novartis; Honoraria (self ), Advisory/Consultancy: Pfizer; Honoraria (self ), Advisory/Consultancy: Roche; Honoraria (self ), IIIc/IV) non-small cell lung cancer (NSCLC) Advisory/Consultancy: Seagen. N. Leighl: Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca. N. Navani: Honoraria (self ): BMS; J. Subramanian1, Y-L. Choi2, T-Y. Chou3,J.Gregg4, R. Hui5, N. Leighl6, Honoraria (self ): Pfizer; Honoraria (self ): Takeda; Honoraria (self ), Advisory/ A. Marchetti7, N. Navani8, T. Bailey9, M. Silvey9, R. Makin9, Consultancy: AstraZeneca; Advisory/Consultancy: Amgen; Advisory/Consultancy: 10 11 10 12 1 Olympus. D.A. Kahangire: Full/Part-time employment: AstraZeneca. M. Chau: D.A. Kahangire , M. Chau , A. Taylor , F. Griesinger Saint Shareholder/Stockholder/Stock options, Full/Part-time employment: 2 Luke’s Cancer Institute, Kansas City, MO, USA; Samsung Medical Center, AstraZeneca; Shareholder/Stockholder/Stock options: Roche. A. Taylor: Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Shareholder/Stockholder/Stock options, Full/Part-time employment: 3Taipei Veterans General Hospital, Taipei, Taiwan; 4University of AstraZeneca. F. Griesinger: Advisory/Consultancy: Roche; Advisory/Consultancy: 5 Boehringer-Ingelheim; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/ California, Davis, CA, USA; Westmead Hospital and the University of Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: 6 Sydney, Sydney, Australia; Princess Margaret Cancer Centre, Toronto, ON, Novartis; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Takeda; Canada; 7Laboratory of Diagnostic Molecular Oncology, Center for Advisory/Consultancy: Merck Sharp & Dohme. All other authors have declared Advanced Studies and Technology (CAST), University of Chieti, Chieti, Italy; no conflicts of interest. 8University College London, London, UK; 9Adelphi Real World, Bollington, UK; 10Global Medical Evidence Generation, AstraZeneca, Cambridge, UK; 11Oncology Business Unit, AstraZeneca, Gaithersburg, MD, USA; 12Pius- 144P Hospital Medical Campus, University of Oldenburg, Oldenburg, Germany Delays in epidermal growth factor receptor mutation (EGFRm) Background: EGFR mutations are known oncogene drivers in NSCLC. testing in advanced (stage IIIb/ IIIc/ IV) non-small cell lung Guidelines recommend EGFRm testing as standard of care in patients cancer (NSCLC) patients and their impact on the use of first with advanced NSCLC. In EGFRm advanced NSCLC patients, EGFR line tyrosine kinase inhibitor (TKIs) in a real-world setting tyrosine kinase inhibitors (EGFR-TKIs) are the preferred first-line 1 2 3 4 5 6 treatment. This study investigated real-world EGFR testing and F. Griesinger , Y-L. Choi , T-Y. Chou , J. Gregg , R. Hui , N. Leighl , 7 8 9 9 9 identified barriers to implementation of testing by surveying physicians’ A. Marchetti , N. Navani , T. Bailey , M. Silvey , R. Makin , 10 11 10 12 1 perceptions. D.A. Kahangire , M. Chau , A. Taylor , J. Subramanian Pius- 2 Methods: An online physician survey was conducted in Australia, Hospital Medical Campus, Oldenburg, Germany; Samsung Medical Canada, Germany, Italy, South Korea, Taiwan, UK and USA (May – Aug Center, Sungkyunkwan University School of Medicine, Seoul, Republic of 3 4 2020). Physicians provided responses on perceptions of EGFR testing Korea; Taipei Veterans General Hospital, Taipei, Taiwan; University of 5 patterns, interpretation of results, treatment decisions and attitudes California, Davis, CA, USA; Westmead Hospital and the University of 6 towards testing in advanced NSCLC patients. Sydney, Sydney, Australia; Princess Margaret Cancer Centre, Toronto, ON, 7 Results: Of the 337 physicians included, 82% were Oncologists or Canada; Laboratory of Diagnostic Molecular Oncology, Center for Pulmonologists (56% Hospital based, 35% Hospital and office/clinic Advanced Studies and Technology (CAST), University of Chieti, Chieti, Italy; 8 9 based, 9% office/clinic based only). Physicians estimated a median 90% University College London, London, UK; Adelphi Real World, Bollington, 10 of advanced patients are tested for common EGFRm (range 80–100% UK; Global Medical Evidence Generation, AstraZeneca, Cambridge, UK; 11 12 between countries). Of physicians who reported not always testing for Oncology Business Unit, AstraZeneca, Gaithersburg, MD, USA; Saint EGFRm, inadequate tissue (47%) and poor performance status (33%) Luke’s Cancer Institute, Kansas City, MO, USA were the main reasons. Physicians estimated a 10 day lapse from biopsy Background: In NSCLC, approximately 10–20% of Caucasian patients to obtaining results; 26% reported dissatisfaction with delay. Physicians and up to 50% of Asian patients harbour EGFRm. Clinical guidelines reported testing for EGFR (and PD-L1) prior to selecting treatment in a recommend EGFRm testing as standard of care in advanced NSCLC, with median 90% of advanced patients. 43% who test prior to selecting EGFR-TKIs recommended as the optimal first-line (1L) treatment option. treatment indicate at least ‘sometimes’ initiating treatment before This study investigated the real-world use of EGFRm testing and the receiving results, of whom 57% reported risk of disease progression as impact of delays in testing had on disease management. the leading factor driving treatment prior to test result. 68% of Methods: A physician survey and chart review conducted in Australia, physicians believed testing delays negatively impact patient outcomes. Canada, Germany, Italy, South Korea, Taiwan, UK and USA (May – Aug Conclusions: Physicians estimated that one in ten advanced NSCLC 2020) included 223 physicians and provided data on 1,793 advanced patients are not tested for EGFR sensitising or activating mutations. NSCLC patients who received a positive first EGFR test result between Many physicians sometimes initiate treatment prior to receiving test Jan – Dec 2017. Data on demographics, clinical characteristics, and results. Testing delays, sample sufficiency, testing turnaround, perform- testing and treatment patterns were abstracted from diagnosis until Mar ance status and risk of progression may result in treatment initiation, 2020 (or death). either without EGFR testing or prior to test results, and may result in Results: Median age at diagnosis was 65 years, 54% were male, 17% patients receiving sub-optimal treatment for advanced disease. had a family history of lung cancer. 56% of patients were smokers or ex- Editorial acknowledgement: Medical writing support under the smokers, (median pack years: 35); 31% had never smoked. 78% of guidance of the authors was provided by Gary Sidgwick of Adelphi patients received their EGFR test result ≤2 weeks following test request, Real World, on behalf of Adelphi Real World and AstraZeneca, and was while 22% waited >2 weeks. Turnaround times (TAT) varied and were funded by AstraZeneca in accordance with Good Publication Practice quicker in South Korea (median 7 days) versus Canada (14 days). Longer (GPP3) guidelines. time from advanced diagnosis to 1L EGFR-TKI initiation was observed in Legal entity responsible for the study: AstraZeneca. patients with a longer TAT for test result (Table). Median time from 1L Funding: AstraZeneca. EGFR-TKI to first subsequent therapy varied and was shorter in ex-Asia Disclosure: J. Subramanian: Honoraria (self ), Advisory/Consultancy: (17.7 months) compared with South Korea (23.1 months). AstraZeneca; Honoraria (self ), Advisory/Consultancy: Boehringer-Ingelheim; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Ely Lilly; Advisory/ Consultancy: Novartis; Advisory/Consultancy: Cardinal Health. Y-L. Choi: Research grant/Funding (institution): AstraZeneca. J. Gregg: Shareholder/ Stockholder/Stock options, Full/Part-time employment, scope of work at Freenome does not have any COI with data or topic of abstract: Freenome; S776 Journal of Thoracic Oncology Vol. 16 No. 4S

Table 144P: Time from advanced diagnosis to 1L EGFR TKI initiation 145P EGFR test turnaround time (weeks) UpSwinG: Real-world, non-interventional cohort study on TKI activity in patients (pts) with EGFR mutation-positive Overall 0–1 1–2 2–3 >3 (EGFRm+) NSCLC with uncommon mutations (n = (n = (n = (n = (n = 743) 266) 298) 147) 32) S. Miura1, T-C. Hsia2, J-Y. Hung3, H.A. Jung4, J-Y. Shih5, T-Y. Yang6, Median time from 4.14 2.71 4.00 5.86 8.79 C-K. Park7, S.H. Lee8, T. Okamoto9, H.K. Ahn10, Y.C. Lee11,Y.Sato12, advanced diagnosis S.S. Lee13, C. Mascaux14, H. Daoud15,A.Märten15, S. Popat16 1Division to 1L EGFR-TKI of Respiratory Medicine, Department of Homeostatic Regulation and (weeks) Development, Niigata University, Niigata, Japan; 2Department of Internal Medicine, China Medical University Hospital, Department of Respiratory Conclusions: A fifth of patients experienced a delay of >2 weeks for Therapy, China Medical University, Taichung, Taiwan; 3Division of EGFR test result, exceeding the recommended ten working day TAT, with Pulmonary and Critical Care Medicine, Department of Internal Medicine, notable country differences observed. There was an association between Kaohsiung Medical University Hospital, Kaohsiung Medical University, TAT for EGFR test result and initiation of 1L EGFR TKI. Further analysis is Kaohsiung, Taiwan; 4Division of Hematology-Oncology, Department of required to understand the impact on patient outcomes. Medicine, Samsung Medical Center, Sungkyunkwan University School of Editorial acknowledgement: Medical writing support under the Medicine, Seoul, Republic of Korea; 5Department of Internal Medicine, guidance of the authors was provided by Gary Sidgwick of Adelphi National Taiwan University Hospital, Taipei, Taiwan; 6Division of Chest Real World, on behalf of Adelphi Real World and AstraZeneca, and was Medicine, Department of Internal Medicine, Taichung Veterans General funded by AstraZeneca in accordance with Good Publication Practice Hospital, Taichung, Taiwan; Faculty of Medicine, School of Medicine, (GPP3) guidelines. National Yang-Ming University, Taipei, Taiwan; 7Department of Internal Legal entity responsible for the study: AstraZeneca. Medicine, Chonnam National University Hwasun Hospital, Hwasun, Funding: AstraZeneca. Republic of Korea; 8Division of Pulmonary and Critical Care Medicine, Disclosure: F. Griesinger: Advisory/Consultancy: Roche; Advisory/Consultancy: Department of Internal Medicine, Kyung Hee University Medical Center, Boehringer-Ingelheim; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/ Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Kyung Hee University School of Medicine, Seoul, Republic of Korea; 9 Novartis; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Takeda; Department of Thoracic Oncology, National Hospital Organization Advisory/Consultancy: Merck Sharp & Dohme. Y-L. Choi: Research grant/ Kyushu Cancer Center, Fukuoka, Japan; 10Division of Medical Oncology, Funding (institution): AstraZeneca. J. Gregg: Shareholder/Stockholder/Stock Gachon University Gil Medical Center, Incheon, Republic of Korea; options, Full/Part-time employment, scope of work at Freenome does not have 11 any COI with data or topic of abstract: Freenome; Speaker Bureau/Expert Department of Internal Medicine, Research Institute of Clinical Medicine testimony: AstraZeneca. R. Hui: Honoraria (self ), Advisory/Consultancy: of Chonbuk National University, Biomedical Research Institute of Chonbuk AstraZeneca; Honoraria (self ), Advisory/Consultancy: Bristol Myers Squibb; National University Hospital, Chonbuk National University Medical School, Honoraria (self ), Advisory/Consultancy: Ely Lilly; Honoraria (self ), Advisory/ Jeonju, Republic of Korea; 12Department of Respiratory Medicine, Kobe Consultancy: Merck Sharp and Dohme; Honoraria (self ), Advisory/Consultancy: 13 Novartis; Honoraria (self ), Advisory/Consultancy: Pfizer; Honoraria (self ), City Medical Center General Hospital, Hyogo, Japan; Inje University Advisory/Consultancy: Roche; Honoraria (self ), Advisory/Consultancy: Seagen. Haeundae Paik Hospital, Inje University College of Medicine, Busan, N. Leighl: Research grant/Funding (institution), Travel/Accommodation/ Republic of Korea; 14Pulmonary Department, Strasbourg University, Expenses: AstraZeneca. N. Navani: Honoraria (self ): BMS; Honoraria (self ): Strasbourg University Hospital, Strasbourg, France; 15Boehringer Pfizer; Honoraria (self ): Takeda; Honoraria (self ), Advisory/Consultancy: 16 AstraZeneca; Advisory/Consultancy: Amgen; Advisory/Consultancy: Olympus. D. Ingelheim International GmbH, Ingelheim Am Rhein, Germany; Lung A. Kahangire: Full/Part-time employment: AstraZeneca. M. Chau: Shareholder/ Unit, Royal Marsden National Health Service Foundation Trust, London, Stockholder/Stock options, Full/Part-time employment: AstraZeneca; United Kingdom; The Institute of Cancer Research, London, UK Shareholder/Stockholder/Stock options: Roche. A. Taylor: Shareholder/ Stockholder/Stock options, Full/Part-time employment: AstraZeneca. Background: EGFR TKIs are established as an effective treatment (tx) J. Subramanian: Honoraria (self ), Advisory/Consultancy: AstraZeneca; Honoraria option for pts with EGFRm+ NSCLC with common (Del19 or L858R) (self ), Advisory/Consultancy: Boehringer-Ingelheim; Advisory/Consultancy: – Pfizer; Advisory/Consultancy: Ely Lilly; Advisory/Consultancy: Novartis; mutations, but limited clinical data exist for EGFR TKI use in the 7 23% Advisory/Consultancy: Cardinal Health. All other authors have declared no of NSCLC tumours with uncommon EGFR mutations. conflicts of interest. Methods: In this non-interventional, global, multi-centre study (NCT04179890), existing medical or electronic health records were identified for consecutive EGFR TKI-naïve pts with uncommon EGFR mutations treated with either erlotinib, gefitinib, afatinib or osimertinib. Endpoints included time to tx failure (TTF), ORR, OS and duration of response (DoR). Results: Pts (n = 246; median age: 69.5 yrs; brain metastases: 7%; ECOG PS ≥2: 16%; Asian: 84%) were recruited from 9 countries. Uncommon mutation categories were: major uncommon (G719X, L861Q, S768I; 73%); compound (35%); ex20ins (12%); T790M (7%); other (9%). Most pts (n = 226; 92%) were treated in 1st-line with an EGFR TKI; 132 (54%), 70 (28%), 35 (14%) and 7 (3%) received afatinib, gefitinib, erlotinib and osimertinib. 57% of pts received >1 line of therapy. Mutations were detected using PCR (75%) or sequencing (25%), mainly based on tissue biopsy (86%). Pathology reports varied in quality, often lacking detail on specific mutations, e.g. ‘ex18’ or ‘ex20ins’. Overall, median TTF with an EGFR TKI was 9.9 mos; afatinib: 11.3 mos; gefitinib: 9.2 mos; erlotinib: 8.2 mos. Overall median OS was 24.4 mos. In pts with major uncommon mutations, median TTF was 14.3 and 9.8 mos with afatinib and 1st-gen TKIs. Median TTF in pts receiving 1st-line chemotherapy was only 4.0 mos. ORR was 42% overall (major: 50%; compound: 49%; other: 44%; T790M: 20%; ex20ins: 17%); afatinib: April 2021 Abstracts S777

44% (DoR: 12.0 mos); 1st-gen TKIs: 44% (DoR: 11.0 mos). More detailed analysis will be presented at the conference. 146P Conclusions: EGFR TKIs were the preferred tx option in pts with The impact of prior immune checkpoint inhibitors or uncommon EGFR mutations. Response was highest in pts with major osimertinib treatment on NSCLC patients receiving uncommon, and/or compound mutations. Data were in line with recent atezolizumab treatment: A real-world observation analyses of afatinib in uncommon mutations. Tx with an EGFR TKI should be considered as standard for pts with uncommon mutations, S-G. Wu1, C-L. Chiang2, C-C. Wang3, J-Y. Hung4, T-C. Hsia5, C-H. Kuo6, although many ex20ins were not responsive. To inform optimal tx J-Y. Shih1 1Internal Medicine Department, National Taiwan University choice, specific details of EGFR mutations must be reported. Hospital, Taipei, Taiwan; 2Chest Medicine, Taipei Veterans General Clinical trial identification: NCT04179890, first posted November 27, Hospital, Taipei, Taiwan; 3Department of Medicine, Chang Gung Memorial 2019. Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan; 4Faculty of Editorial acknowledgement: Medical writing assistance, supported Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, financially by Boehringer Ingelheim, was provided by Steven Kirkham, of Taiwan; 5Department of Internal Medicine, China Medical University GeoMed, an Ashfield company, part of UDG Healthcare plc, during the Hospital, Department of Respiratory Therapy, China Medical University, development of this abstract. Taichung, Taiwan; 6Chang Gung Memorial Hospital, Taipei, Taiwan Legal entity responsible for the study: Boehringer Ingelheim. Funding: Boehringer Ingelheim. Background: Cancer Immunotherapy has become the standard treat- Disclosure: S. Miura: Speaker Bureau/Expert testimony: Boehringer Ingelheim ment for non-small cell lung cancer (NSCLC) recently. Atezolizumab Inc.; Speaker Bureau/Expert testimony: MSD Inc.; Speaker Bureau/Expert (atezo) demonstrated survival benefit and has been approved in 1L/2L+ testimony: Elli Lilly Japan; Speaker Bureau/Expert testimony: Ono Pharma. Inc; Speaker Bureau/Expert testimony: Chugai Pharm Inc. J-Y. Shih: Honoraria (self ): NSCLC. This study aimed to explore the clinical prognostic factors of AstraZeneca; Honoraria (self ), Research grant/Funding (self ): Roche; Honoraria NSCLC patients receiving atezo-containing regimens in the 2L+ setting. (self ): Boehringer Ingelheim; Honoraria (self ): Eli Lilly; Honoraria (self ): Pfizer; Methods: We retrospectively collected NSCLC patients who were treated Honoraria (self ): Novartis; Honoraria (self ): Merck Sharp & Dohme; Honoraria with atezo from 2017 to 2019 in 6 medical centers in Taiwan. Clinical (self ): Ono Pharmaceutical; Honoraria (self ): Chugai; Honoraria (self ): Bristol- Myers Squibb. T. Okamoto: Honoraria (self ): AstraZeneca; Honoraria (self ), characteristics, treatment course, and responses of patients were Research grant/Funding (institution): Eli Lilly Japan; Honoraria (self ): Johnson & recorded. Johnson; Honoraria (self ), Research grant/Funding (institution): MSD; Honoraria Results: There were 128 NSCLC patients who have received 2L+ atezo, (self ), Research grant/Funding (institution): Nippon Boehringer Ingelheim; including 38 (30%) patients in 2L and 90 (70%) in 3L+ setting. The Honoraria (self ), Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Chugai Pharmaceutical; Research grant/ outcomes of atezo-containing regimens were response rate 10.2%, Funding (institution): Covidien Japan; Research grant/Funding (institution): median progression-free survival (mPFS) 3.5 (95% confidence interval Novartis Pharma; Research grant/Funding (institution): Ono Pharmaceutical; [CI]: 2.9–4.1) months, and median overall survival (mOS) 10.7 (95% CI: Research grant/Funding (institution): Pfizer Japan. H.K. Ahn: Speaker Bureau/ 9.4–12.0) months. Thirteen of 128 (10%) patients with prior immune Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Lilly. Y. Sato: Honoraria (self ): Chugai Phama; Honoraria checkpoint inhibitors (ICIs) treatment before atezo-containing regimens (self ): MSD; Honoraria (self ): Ono Pharmaceutical CO; Honoraria (self ): Novartis; had shorter mPFS (2.4 months versus 3.5 months; p = 0.009) and mOS Honoraria (self ): Taiho Pharmaceutical; Honoraria (self ): AstraZeneca; Honoraria (5.4 months versus 12.0 months; p < 0.001) than those without prior (self ): Nippon Kayaku. C. Mascaux: Honoraria (self ), Travel/Accommodation/ ICIs treatment. Multivariate analysis of the prognostic factors for Expenses: Roche; Honoraria (self ), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self ): Kephren; Honoraria (self ): Bristol-Myers Squibb; survival revealed that prior ICIs treatment (hazard ratio [HR]: 2.61; Honoraria (self ): Merck Sharp & Dohme; Honoraria (self ): Pfizer; Travel/ p = 0.003) and poor performance status (HR: 3.17; p < 0.001) were Accommodation/Expenses: Boehringer Ingelheim; Travel/Accommodation/ associated with poor prognosis. In addition, there were 34 patients with Expenses: Takeda. H. Daoud: Full/Part-time employment: Boehringer Ingelheim EGFR-mutant non-squamous NSCLC who had received EGFR-TKIs International GmbH. A. Märten: Full/Part-time employment: Boehringer Ingelheim. S. Popat: Advisory/Consultancy, Research grant/Funding (institution), Consulting before atezo treatment, including 9 patients who have been treated fees and Corporate-sponsored research: AstraZeneca; Advisory/Consultancy, with osimertinib. The patients with osimertinib treatment before atezo Research grant/Funding (institution), Consulting fees and Corporate-sponsored had shorter mPFS (2.8 months versus 4.8 months; p = 0.010) and mOS research: Roche; Advisory/Consultancy, Research grant/Funding (institution), (12.0 months versus 5.4 months; p < 0.001) than those without Consulting fees and Corporate-sponsored research: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and osimertinib treatment. Multivariate analysis also revealed an association Corporate-sponsored research: Pfizer; Advisory/Consultancy, Research grant/ of shorter OS with osimertinib treatment before atezo (HR: 5.49; 95% CI: Funding (institution), Consulting fees and Corporate-sponsored research: Novartis; 1.76–17.14; p = 0.003). Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Conclusions: ICIs and osimertinib treatment before atezolizumab Corporate-sponsored research: Takeda; Advisory/Consultancy, Research grant/ Funding (institution), Consulting fees and Corporate-sponsored research: BMS; treatment were poor prognostic factors in NSCLC patients. Further Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and studies with larger sample sizes are needed to validate this observation. Corporate-sponsored research: MSD; Advisory/Consultancy, Research grant/ Legal entity responsible for the study: This study was managed by Funding (institution), Consulting fees and Corporate-sponsored research: EMD Formosa Biomedical Technology Corp. contract research organization Serono; Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and Corporate-sponsored research: Bayer; Advisory/Consultancy, Research and overseen by Roche Products Ltd., Taiwan. grant/Funding (institution), Consulting fees and Corporate-sponsored research: Funding: This study was sponsored by Roche Products Ltd. Blueprint; Advisory/Consultancy, Research grant/Funding (institution), Disclosure: S-G. Wu: Honoraria (self ): Roche; Honoraria (self ): AstraZeneca; Consulting fees and Corporate-sponsored research: Daiichi Sankyo; Advisory/ Honoraria (self ): Pfizer. C-L. Chiang: Honoraria (self ): Roche; Honoraria (self ): Consultancy, Research grant/Funding (institution), Consulting fees and Corporate- Boehringer Ingelheim; Honoraria (self ): AstraZeneca. T-C. Hsia: Research grant/ sponsored research: Guardant Health; Advisory/Consultancy, Research grant/ Funding (self ): Eli Lilly. J-Y. Shih: Honoraria (self ), Advisory/Consultancy, Travel/ Funding (institution), Consulting fees and Corporate-sponsored research: Janssen; Accommodation/Expenses: Roche; Honoraria (self ), Advisory/Consultancy: Advisory/Consultancy, Research grant/Funding (institution), Consulting fees and AstraZeneca; Honoraria (self ), Advisory/Consultancy: Boehringer Ingelheim; Corporate-sponsored research: GSK; Advisory/Consultancy, Consulting fees: Honoraria (self ), Advisory/Consultancy: Eli Lilly; Honoraria (self ), Advisory/ BeiGene; Advisory/Consultancy, Consulting fees: Incyte; Advisory/Consultancy, Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Consulting fees: Eli Lilly; Advisory/Consultancy, Consulting fees: Amgen; Research Honoraria (self ), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (self ), grant/Funding (institution), Corporate-sponsored research: Ariad; Research grant/ Advisory/Consultancy, Travel/Accommodation/Expenses: Chugai Funding (institution), Corporate-sponsored research: Clovis; Research grant/ Pharmaceutical; Honoraria (self ), Advisory/Consultancy, Travel/ Funding (institution), Corporate-sponsored research: Celgene; Research grant/ Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self ), Travel/ Funding (institution), Corporate-sponsored research: Epizyme; Research grant/ Accommodation/Expenses: Pfizer; Honoraria (self ): Novartis. All other authors Funding (institution), Corporate-sponsored research: Mirati; Research grant/ have declared no conflicts of interest. Funding (institution), Corporate-sponsored research: Trizel; Research grant/ Funding (institution), Corporate-sponsored research: Turning Point Therapeutics. All other authors have declared no conflicts of interest. S778 Journal of Thoracic Oncology Vol. 16 No. 4S

147P 148P PD-L1 expression influenced by osimertinib treatment in Neutrophil to lymphocyte ratio as a prognostic factor in advanced EGFR T790M-positive non-small cell lung cancer epidermal growth factor receptor-mutant non-small cell lung patients cancer treated with tyrosine kinase inhibitor: A systematic review and meta-analysis Y. Yu1, L. Xia1, J. Zhou2, K. Wang3, Y. Zhang4, C. Zhang5, A. Liu6, Y. Fan4, J. Chang7, L. Wang8,Y.Liu9,S.Lu1 1Shanghai Lung Cancer R.S. Heriyanto1, J. Tandiono1, E. Marcella1, B. Susanto1, S. Chen1, Center, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong F. Wijovi1, A. Tancherla1, A. Kurniawan2 1Faculty of Medicine, Pelita University, Shanghai, China; 2Respiratory Disease, Thoracic Disease Harapan University, Tangerang, Indonesia; 2Department of Internal Center, The First Affiliated Hospital, College of Medicine, Zhejiang Medicine, Pelita Harapan University, Tangerang, Indonesia University, Hangzhou, China; 3Respiratory Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Background: Recent studies have shown the prognostic value of pre- 4Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China; treatment NLR in advanced cancers; However, the role of NLR in patients 5Oncology, Inner Mongolia People’s Hospital, Huhhot, China; 6Oncology, with epidermal growth factor receptor (EGFR)-mutant non-small cell The Second Affiliated Hospital of Nanchang University, Nanchang, China; lung cancer (NSCLC) treated with tyrosine kinase inhibitor (TKI) 7Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, remains unclear. Thus, this study aims to investigate the association China; 8The Comprehensive Cancer Centre of Drum Tower Hospital, between pre-treatment NLR with outcomes in EGFR-mutant NSCLC Nanjing, China; 9Medical Oncology, The First Hospital of China Medical patients. University, Shenyang, China Methods: We searched data from PMC, PubMed, Google Scholar, Science Direct, and Scopus, on January 5th, 2021 using a combination of Background: Anti-PD-1/L1 antibodies could be an optional therapy for keywords associated with advanced NSCLC with EGFR mutation, EGFR-TKI-resistant non-small cell lung cancer (NSCLC) patients with treatment using TKI, and neutrophil-lymphocyte ratio in relation to EGFR mutation. However, little is known about PD-L1 expression in their outcome. Publications included are limited to English manuscripts advanced NSCLC patients with the T790M-positive EGFR mutation, as that were published in the past 10 years, and exclusion criteria are well as the changes induced by osimertinib treatment. NSCLC patients without EGFR mutation and not treated with TKI. All Methods: From July 2017 to February 2020, 63 advanced NSCLC studies are reviewed and evaluated by all 7 authors. The quality of each patients with T790M-positive EGFR mutation were screened and included study was assessed using the Newcastle-Ottawa Scale (NOS) enrolled in the study to receive osimertinib treatment at 80 mg orally and GRADE. once daily. PD-L1 expression on tumor cells at baseline and after Results: A total of 10 retrospective studies consisting of 1532 EGFR progression was evaluated by immunohistochemistry with VENTANA mutated NSCLC patients treated with TKI were included. All 10 included PD-L1 (SP263) assay. study were of good quality, based on GRADE this study is moderate in Results: The mean age of the 63 enrolled patients was 61.4±10.77 years, quality as there are minimal inconsistency and variability in results and including 29 males (46.0%) and 34 females (54.0%). All patients were there are no publication biases. 9 studies showed that higher pre- Chinese and most of them were advanced NSCLC patients with treatment NLR is associated with significantly worse OS and PFS. 1 study adenocarcinoma (60/63, 95.2%). The osimertinib treatment duration showed that in patients treated with TKI, NLR is not a significant and follow-up time ranged from 6 to 126 weeks. At baseline, the positive prognostic factor of OS, nor PFS. Pooled analysis showed that high NLR is rate of PD-L1 expression on tumor cells with different cut-off points significantly associated with worse OS and PFS (HR = 1.65; 95% CI, (≥1%, ≥25%, ≥50%) was 34.1% (14/41), 4.9% (2/41), and 4.9% (2/ 1.18–2–31; p < 0.00001, HR = 1.52; 95% CI, 1.16–1.99; p < 0.00001) 41), respectively. After progression, among 12 samples tested for PD-L1 when compared with those with low NLR. expression, 41.7% (5/12), 16.7% (2/12) and 8.3% (1/12) were PD-L1 Conclusions: Current studies demonstrated that high pre-treatment positive on tumor cells with cut-off points at 1%, 25% and 50%, NLR is significantly associated with worse OS and PFS compared to low respectively. Ten patients with samples tested both at baseline and after pre-treatment NLR, making it a promising biomarker for the prognosis of progression were analyzed for the change of PD-L1 expression. The EGFR mutated NSCLC patients treated with TKI, which warrants further mean change in the positive rate of PD-L1 expression from baseline to prospective investigation. progression was 9.05% (95% CI: -4.895%, -22.995%, P = 0.0625, n = Legal entity responsible for the study: Rivaldo Steven Heriyanto. 10). Among these 10 patients, PD-L1 expression on tumor cells were all Funding: Has not received any funding. negative (< 1%) at baseline, but 50%≥5/10, ≥ 1% expression), 20%≥2/ Disclosure: All authors have declared no conflicts of interest. 10, ≥25%) and 10%≥1/10, ≥50%≥of them were positive after progression. Conclusions: We observed that PD-L1 expression on tumor cells tended to increase after osimertinib treatment in advanced EGFR T790M- positive NSCLC patients, which may provide clues for optimization of subsequent anti-PD-1/L1 treatment. The effect of osimertinib treatment on PD-L1 expression in EGFR T790M-positive NSCLC patients warrants further validation in study with a larger population. Legal entity responsible for the study: Guangdong Association of Clinical Trails (GACT) Chinese Thoracic Oncology Group (CTONG). Funding: AstraZeneca. Disclosure: All authors have declared no conflicts of interest. April 2021 Abstracts S779

149P 150P First-line (1L) osimertinib in EGFR mutant (mut) advanced A phase I study of TQ-B2450, a PD-L1 mAb, plus anlotinib in non-small cell lung cancer (aNSCLC) patients (pts): EGFR+ advanced NSCLC patients failed to prior EGFR TKI Progression (PD) pattern and safety in the real-world (RW) therapies

M. Lorenzi1, A. Dal Maso1, A. Ferro1,V.Polo2, D. Scattolin1, J. Feng, M. Shi, L. Wang, S. Yu, F. Yan, W. Peng Jiangsu Cancer Hospital, M. Macerelli3, A. Follador3, G. Targato3, S. Indraccolo4, S. Frega5, Nanjing, China J. Menis1, L. Bonanno5, V. Guarneri1, P.F. Conte1, G. Pasello1 1 Background: Platinum-based chemotherapy is the standard therapy for Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; 2Oncology Unit, AULSS 2 Marca Trevigiana, Ca’ the patients(pts) with EGFR-mutation-positive advanced NSCLC failed 3 to prior EGFR TKI therapies. However, the IMpower150 study subgroup Foncello Hospital, Treviso, Italy; Department of Medical Oncology, analyses show Atezolizumab (PD-L1) plus bevacizumab and chemo- Azienda Sanitaria Universitaria Integrata of Udine - Santa Maria della Misericordia Hospital, Udine, Italy; 4Immunology and Molecular Oncology therapy improved overall survival in EGFR TKI treated NSCLC. TQ-B2450 5 is a humanized PD-L1 mAb, anlotinib, an antiangiogenic multi-target Unit, Veneto Institute of Oncology IOV – IRCCS, Padua, Italy; Division of Medical Oncology 2, Veneto Institute of Oncology IOV – IRCCS, Padua, Italy TKI. This ongoing phase I study aimed to assess the safety and effect of TQ-B2450 plus anlotinib in EGFR+ advanced NSCLC pts failed to prior Background: RW data on PD pattern and safety of 1L osimertinib in EGFR TKI therapies. EGFR mut aNSCLC are currently lacking. Methods: Pts with EGFR+ advanced NSCLC who failed to prior EGFR TKI Methods: This is an observational, multicenter study enrolling EGFR therapies were eligible. Pts with previous received platinum-based mut aNSCLC receiving 1L osimertinib between November 2018 and chemotherapy were excluded. Anlotinib was given orally for 2 weeks of a 2020. Primary endpoints were treatment outcomes: median progression 21-day cycle (days 1–14), with TQ-B2450 given at 1200 mg every 3 free survival (mPFS), time to treatment failure (mTTF) and PD patterns. weeks on day 1. A standard 3+3 dose escalation design was used to Safety profile was also recorded as a secondary endpoint. PD was evaluate various doses of anlotinib in combination with TQ-B2450 to classified as isolated (single lesion PD), oligoprogression (oligoPD; PD in determine the RP2D. Secondary endpoints were ORR, DCR and PFS. ≤ 3 lesions in ≤ 2 sites), systemic all others. Results: From 11/2019–6/2020, 9 pts were enrolled. During anlotinib Results: At data cut-off (January 5, 2021), 82 pts receiving osimertinib dose-escalation, pts received doses of 8 mg (n = 3), 10 mg (n = 3) and were included in 3 centres: 52 (63.4%) were female, 46 (56.1%) never 12 mg (n = 3). No DLTs were observed. The most common grade 1–2 smokers. Baseline EGFR mutations were exon 19 deletion in 39 (47.6%) adverse events (AEs) included Hand and foot skin reaction (33.3%) and pts, L858R in 36 (43.9%) pts, others in 7 (8.6%) pts. ECOG performance proteinuria (22.2%). Only two Grade 3 AEs which was hypertension. status was 0–1 in 65 (79.3%) pts. Number (N) of metastatic sites at Among 9 evaluable pts, DCR was 77.8% (7/9) and the other 2 pts had diagnosis was <3 in 52 (63.4%) pts, ≥ 3 in 30 (35.6%) pts; 27 (32.9%) disease progression, the median PFS was 9.1 months (95% CI [4.2. 9.3]). pts had brain metastases. Median follow-up was 11.2 months (mo). Conclusions: TQ-B2450 plus anlotinib was well tolerated with evidence Response rate was 68.3%, disease control rate 86.6%. mPFS was 22.0 mo of clinical activity. Based on dose exploration, 12 mg is the RP2D. Further (95%CI, 11.4–32.5), mTTF 25.3 mo (95%CI, 18.9-not calculable). PD evaluation is warranted for pts with EGFR+ advanced NSCLC who failed was reported in 28 (34%) pts; median N of PD sites was 2 (range 1–7); to prior EGFR TKI therapies. the most frequent PD sites were lung (N = 19, 67.9%), bone (N = 11, Clinical trial identification: ChiCTR1900026273. 39.3%) and brain (N = 7, 25%). New PD sites were present in 11 Legal entity responsible for the study: The authors. (39.3%) pts; median N = 1 (range 1–4). Isolated PD was observed in Funding: Has not received any funding. 5 (17.9%) pts, oligoPD in 6 (24.4%) and systemic in 16 (57.1%). 9 cases Disclosure: All authors have declared no conflicts of interest. underwent tissue and/or liquid rebiopsy at PD. Druggable resistance mechanisms were identified in 5 pts: MET amplification (amp) (N = 3), MET amp/EGFR amp (N = 1) and HER2 amp (N = 1). The most frequent 151P any grade (G) adverse events (AEs) were diarrhea (N = 33, 40.2%), rash Osimertinib versus standard-of-care EGFR-TKI as first-line (N = 32, 39.0%), paronychia (N = 22, 26.8%) and creatinine increase treatment for advanced NSCLC with EGFR-positive mutation (N = 25, 30.5%). The most frequent G3/4 AEs were thromboembolic events (N = 6, 7.3%), diarrhea (N = 4, 4.9%), arterial thromboembolism patients: A systematic review

(N = 2, 2.4%) and rash (N = 2, 2.4%). 1 1 1 1 1 Conclusions: Osimertinib confirmed efficacy and safety in RW. S. Chen , E. Marcella , B. Susanto , J. Tandiono , R.S. Heriyanto , F. Wijovi1, A. Tancherla1, A. Kurniawan2 1Faculty of Medicine Pelita Thromboembolic events were observed more frequently than previously 2 reported. The study is still ongoing in order to recruit a larger patient Harapan University, Tangerang, Indonesia; Department of Internal population. Medicine, Pelita Harapan University, Tangerang, Indonesia Legal entity responsible for the study: Veneto Institute of Oncology Background: Brain metastases are a very common complication in – IOV IRCCS. patients with non-small cell lung cancer (NSCLC) with epidermal growth Funding: Has not received any funding. factor receptor (EGFR)-positive mutation. The existence of the blood- Disclosure: All authors have declared no conflicts of interest. brain barrier makes it difficult for chemotherapeutic agents with poor penetrability to work. Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKIs), is reported to have better penetration ability and potency compared to the standard-of-care EGFR TKIs (gefitinib and erlotinib). This study investigates the efficacy of osimertinib compared to other EGFR TKIs. Methods: On January 4th 2021, data was collected from PMC, PubMed, Google Scholar, Science Direct, and Scopus, using a combination of keywords associated with advanced NSCLC and treatment using EGFR TKI in relation to their efficacy. Included publications were limited to those published in the last 10 years with English manuscripts and were S780 Journal of Thoracic Oncology Vol. 16 No. 4S all reviewed and evaluated by the authors. All included studies are Legal entity responsible for the study: Medscape. clinical trials with an inclusion criteria of adult (≥18 years old) patients Funding: The educational activity was supported by an independent with untreated NSCLC with EGFR-positive mutation, and exclusion educational grant from Janssen. criteria of any patients with brain metastases who were neurologically Disclosure: All authors have declared no conflicts of interest. unstable. The quality of each studies was assessed using the Newcastle- Ottawa Scale (NOS) and all included studies were good in quality according to the NOS. 153P Results: All 5 studies with a total of 998 patients claimed that Real-world study of NSCLC with EGFR exon 20 insertions osimertinib showed efficacy superior to the standard EGFR TKIs used in the first-line treatment of advanced EGFR mutation-positive NSCLC. One P. Christopoulos1, C. Grohé2, F. Griesinger3, R.F. Falkenstern-Ge4, study specified that although osimertinib is superior in terms of efficacy, J. Krisam5, L. Brückner6, M. Wermke7, D. Misch8, B. Hackanson9, key symptom improvements did not favour any of the EGFR TKIs. M. Faehling10, A. Tufman11, M. Janning12, C. Schulz13, M. Reck14, Conclusions: Osimertinib is proven to be superior in terms of efficacy J-L. Hong15, H.M. Lin15, A. Stenzinger16, M. Thomas1 1Thoracic compared to gefitinib and erlotinib, the standard-of-care EGFR TKIs. It Oncology, Thoraxklinik, University Hospital Heidelberg and Translational also has a similar safety profile despite a longer duration of exposure and Research Center Heidelberg, Member of the German Center for Lung therefore should be considered for first-line therapy in advanced NSCLC Research (DZL), Heidelberg, Germany; 2Evangelische Lungenklinik, Berlin, patients who are EGFR-mutation positive. Germany; 3Hematology and Oncology, Pius-Hospital Medical Campus, Legal entity responsible for the study: The authors. University of Oldenburg, Oldenburg, Germany; 4Thoracic Oncology, Robert Funding: Has not received any funding. Bosch Center for Tumor Diseases (RBCT), Stuttgart, Germany; 5Institute of Disclosure: All authors have declared no conflicts of interest. Medical Biometry and Informatics, University Hospital Heidelberg, Heidelberg, Germany; 6Thoracic Oncology, Thoraxklinik, University Hospital Heidelberg, Heidelberg, Germany; 7Thoracic Oncology, Dresden 152P University Hospital, Dresden, Germany; 8Lungenklinik Heckeshorn, Helios Effect of online continuing education on oncologists’ Hospital Emil von Behring, Berlin, Germany; 9Hematology/Oncology, knowledge regarding resistance to EGFR TKIs in NSCLC University Medical Center Augsburg, Augsburg, Germany; 10Cardiology/ Pneumology, Klinikum Esslingen, Esslingen am Neckar, Germany; N. Dorkhom1, A. Furedy2, P. Chen3 1Oncology Global, Medscape, 11Pneumology, LMU Klinikum der UniversitätMünchen, Munich, Germany; Naarden, Netherlands; 2Medscape, Atlanta, GA, USA; 3Medscape, 12Personalized Oncology, University Hospital Mannheim and German New York, NY, USA Cancer Research Center (DKFZ), Mannheim/Heidelberg, Germany; 13Clinic and Polyclinic for Internal Medicine II, University Hospital Regensburg, Background: Resistance to EGFR TKIs remains a major challenge in Regensburg, Germany; 14Thoracic Oncology, LungClinic Grosshansdorf advanced NSCLC. The objective of this study was to assess if an online, and Airway Research Center North, Member of the German Center for continuing education activity could improve the knowledge of oncolo- Lung Research (DZL), Grosshansdorf, Germany; 15Millennium gists regarding the biology and emerging strategies for de novo and Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda acquired resistance to EGFR TKIs in NSCLC. Pharmaceutical Company Limited, Cambridge, MA, USA; 16Institute of Methods: This educational activity consisted of a 15-minute video Pathology, University Hospital Heidelberg, Heidelberg, Germany presentation with synchronized slides. Educational effectiveness was assessed with a repeated-pairs pre-/post-assessment study design using Background: EGFR exon 20 insertions occur in up to 2% of non-small- 3 knowledge questions and 1 confidence question, in which each cell lung cancers (NSCLC) and confer resistance to currently approved individual served as his/her own control. A chi-squared test assessed targeted therapies (TKI). Due to the lack of specific treatment options, significance of improvement in the percentage of correct responses to these alterations have been underreported, so that characteristics and knowledge questions from pre- to post-assessment. P values <0.05 are outcome in the routine setting remain unclear. statistically significant. The activity launched on 5th of June, 2020, with Methods: This is a medical chart review study of 104 stage IV NSCLC data collected through August 18, 2020 being reported in the current patients with EGFR exon 20 mutations treated in 12 German academic study. centers. Tumor response was evaluated by review of radiologic images Results: The analysis set consisted of responses from oncologists (n = based on RECIST v1.1. 91) who answered all assessment questions during the study period. Results: The median age at diagnosis was 66 years, with a Analysis of pre- vs post-intervention responses demonstrated a preponderance of females (68/104), never/light-smokers (<10 pack- significant improvement in overall knowledge of oncologists (P < years, 59/94 evaluable cases), adenocarcinomas (99/104), and a 0.001). Average correct responses increased from 34% pre to 68% baseline ECOG status of 0/1 (88%). The overall response rate (ORR) post education. Specific areas of improvement in knowledge include: - and confirmed ORR (cORR) were 16% and 13% in the first, and 7% and Acquired resistance mechanisms to 3rd generation TKIs (pre 33%, post 5% in the second line (n = 57), respectively. Disease control rates (DCR) 70%; P < 0.001) - Mechanism of action of novel therapies targeting were 77% in the first, and 51% in the second line. Median progression- resistance (pre 59%, post 82%; P < 0.001) - Clinical trial data for novel free survival (PFS) was 6.3 months in the first and 3.0 months in the therapies targeting NSCLC with EGFR exon 20 insertions (pre 9%, post second-and-later lines. Patients treated initially with platinum-based 52%; P < 0.001) After education, 57% of oncologists had a measurable CHT had a second-line ORR of 2% (9% under mono-CHT, n = 11, 0% increase in confidence and average confidence in understanding the under other therapies; cORR = 0%, n = 43) and DCR of 51%, with a clinical implications of de novo and acquired resistance to EGFR TKIs median PFS of 3.0 months in the second-and-later lines. Median overall increased by 35%. survival from start of the first line was 17.8 months in the entire cohort, Conclusions: This study demonstrated the success of an online, 15- and 18.8 months in the post-platinum subset. minute educational activity in improving the knowledge and confidence of oncologists regarding biology and emerging strategies for de novo and acquired resistance to EGFR TKIs in NSCLC. April 2021 Abstracts S781

Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self ), Table 153P Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Honoraria (self ), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self ), ORR % (n) cORR % (n) DCR % (n) PFS * OS * Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria st nd st nd st nd st nd line 1 2 1 2 1 2 1 2 from (self ), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; & start Honoraria (self ), Travel/Accommodation/Expenses: Chugai; Honoraria (self ), st Travel/Accommodation/Expenses: Celgene. All other authors have declared no later of 1 conflicts of interest. all patients 16 (104) 7 (57) 13 (103) 5 (57) 77 (104) 51 (57) 6.3 3.0 17.8 (4.7– (2.1– (13.9– 8.0) 4.0) 21.7) by treatment 154P CHT 25 (53) 17 (24) 19 (52) 13 (24) 87 (53) 71 (24) 7.8 4.1 18.4 Intracranial efficacy of alectinib in ALK-positive NSCLC (6.2– (3.2– (15.2– 9.5) 5.0) 21.5) patients with CNS metastases: A multicenter retrospective CHT/IO 25 (16) 0 (4) 19 (16) 0 (4) 75 (16) 75 (4) 5.6 6.3 n.r. study (2.9– (1.9– 8.2) 10.6) Z. Zou1, P. Xing1, X. Hao1,Y.Wang1, L. Shan2, C. Zhang3, X. Song4, IO 0 (7) 0 (10) 0 (7) 0 (10) 43 (7) 30 (10) 4.2 2.1 24.7 K. Ma5, Z. Liu5, G. Dong6,J.Li1 1Department of Thoracic Oncology, (0– (1.3– (7.2– Chinese Academy of Medical Sciences and Peking Union Medical College - 10.1) 2.9) 42.2) National Cancer Center, Cancer Hospital, Beijing, China, 2Department of EGFR TKI 0 (28) 0 (19) 0 (28) 0 (19) 68 (28) 32 (19) 3.8 3.0 12.6 – – – Thoracic Oncology, Tumor Hospital Affiliated to Xinjiang Medical (1.9 (1.8 (6.7 3 5.8) 4.3) 18.5) University, Urumqi, China; Cancer Center, Inner Mongolia Autonomous ‘ 4 post- - 2 (43) - 0 (43) - 51 (43) - 3.0 18.8 Region People s Hospital, Huhhot, China; Department of Respiratory 5 platinum (2.5– (16.3– Medicine, Shanxi Provincial Cancer Hospital, Taiyuan, China; Cancer 6 3.6) 21.2) Center, The First Hospital of Jilin University, Changchun, China; Oncology Department, Tangshan People’s Hospital, Tangshan, China n.r.: not reached; abbreviations defined in text * months (95% confidence interval). Background: CNS metastases in patients with ALK-positive NSCLC are a Conclusions: Currently, there is no standard of care for NSCLC patients cause of substantial morbidity and mortality. Alectinib had demon- with EGFR exon 20 insertions, the majority of whom initially receives strated promising intracranial efficacy in several prospective clinical CHT. The median PFS of approximately 6 months and median OS of 1.5 trials. But there was limited data on intracranial response of Alectinib in years from start of first-line therapy are comparable to historical NSCLC real world setting. controls. Conventional EGFR TKI or IO do not appear to be effective, Methods: In this retrospective study, ALK+ NSCLC patients with brain highlighting the need for novel targeted therapies. metastases (BM) or leptomeningeal metastases (LM) from six hospitals Legal entity responsible for the study: Thoraxklinink Heidelberg were divided into three cohorts based on treatment history and gGmbH progression pattern. Cohort 1 was ALK-TKI naive patients, Cohort 2 Funding: Takeda Pharmaceutical Company Limited. was patients who experienced intracranial progression with or without Disclosure: P. Christopoulos: Honoraria (self ), Advisory/Consultancy, Research extracranial progression following prior crizotinib, and Cohort 3 was grant/Funding (self ): Takeda; Honoraria (self ), Advisory/Consultancy, Research patients who progressed only in CNS following prior treatment with grant/Funding (self ): AstraZeneca; Honoraria (self ), Advisory/Consultancy, other second-generation ALK inhibitors. The definition of CNS target Research grant/Funding (self ): Novartis; Honoraria (self ), Advisory/ lesions and assessment of intracranial efficacy were based on RECIST 1.1. Consultancy, Research grant/Funding (self ): Roche; Honoraria (self ), Advisory/ Consultancy: Boehringer Ingelheim; Honoraria (self ), Advisory/Consultancy: Results: 65 patients were eligible and included in our study (cohort 1: 20, Chugai; Honoraria (self ), Advisory/Consultancy: Pfizer. C. Grohe:́ Honoraria cohort2: 32, cohort3: 13), among patients with CNS target lesion (defined (self ), Advisory/Consultancy: Takeda. M. Wermke: Honoraria (self ), Advisory/ as ≥1 cm CNS lesion) in the baseline, intracranial overall response rate(ic- Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self ): Merck; ORR) was 82% (9/11), 76.5% (13/17), 43% (3/7) in each cohort. Honoraria (self ), Advisory/Consultancy: Roche; Honoraria (self ), Advisory/ Consultancy: Novartis; Honoraria (self ), Advisory/Consultancy: Kite; Advisory/ Maximum shrinkage rate of CNS target lesions in three cohorts were also Consultancy: Heidelberg Pharma; Honoraria (self ), Travel/Accommodation/ summarized in the table. In each cohort, 75% (6/8), 77% (10/13), 83% Expenses: AstraZeneca; Honoraria (self ), Advisory/Consultancy: Boehringer (5/6) patients were reported to have significant improvement in Ingelheim; Travel/Accommodation/Expenses: Glenmark. A. Tufman: Honoraria symptoms attributable to CNS metastases respectively. 9 patients with (self ), Advisory/Consultancy: Lilly; Honoraria (self ), Advisory/Consultancy: AstraZeneca; Honoraria (self ), Advisory/Consultancy: Roche; Honoraria (self ), LM demonstrated 100% intracranial disease control rate and all of them Advisory/Consultancy: Takeda; Honoraria (self ), Advisory/Consultancy: Celgene; experienced significant improvement in CNS related symptoms. Honoraria (self ), Advisory/Consultancy: BMS; Honoraria (self ), Advisory/ Intracranical time to tumor progression were still not reached with the Consultancy: MSD; Honoraria (self ), Advisory/Consultancy: Pfizer; Honoraria median follow upof 13.2 months, 16.7 months, 10.4 months in each cohort. (self ), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self ), Advisory/ Consultancy: GSK; Honoraria (self ), Advisory/Consultancy: Amgen. C. Schulz: Conclusions: Our results indicated that Alectinib showed substantial Honoraria (self ), Honoraria (institution), Advisory/Consultancy, Travel/ intracranial activity in ALK-positive patients with CNS metastases Accommodation/Expenses: Takeda. M. Reck: Honoraria (self ): Amgen; regardless of their intracranial disease condition or previous ALK-TKI Honoraria (self ): AstraZeneca; Honoraria (self ): BMS; Honoraria (self ): treatment history. Boehringer Ingelheim; Honoraria (self ): Lilly; Honoraria (self ): Merck; Honoraria (self ): MSD; Honoraria (self ): Novartis; Honoraria (self ): Pfizer; Honoraria (self ): Roche; Honoraria (self ): Samsung. J-L. Hong: Full/Part-time Table 154P employment: Millennium Pharmaceuticals, Inc., Cambridge, MA, USA. H.M. Lin: Full/Part-time employment: Takeda. A. Stenzinger: Honoraria (self ), Advisory/ Cohort1 Cohort2 Cohort3 Consultancy: BMS; Honoraria (self ), Advisory/Consultancy: AstraZeneca; Honoraria (self ), Advisory/Consultancy: ThermoFisher; Honoraria (self ), ic-ORR in patients 55% [95% 53% [95% 38.5% [95% – – – Advisory/Consultancy: Novartis; Honoraria (self ): Illumina; Honoraria (self ): with or without CNS CI:31.5% 76.9%] CI:34.7% CI:13.9% 68.4%] MSD; Honoraria (self ): Roche; Research grant/Funding (self ): Chugai. M. Thomas: target lesions (11/20) 74.9%] (17/32) (5/13) Honoraria (self ), Advisory/Consultancy, Research grant/Funding (institution), ic-ORR in patients 82% [95% 76.5% [95% 43% [95%CI:9.9% Travel/Accommodation/Expenses: BMS; Honoraria (self ), Advisory/Consultancy, with CNS target CI:48.2%–97.7%] CI:50.1%– %–81.6%] (3/7) Research grant/Funding (institution), Travel/Accommodation/Expenses: lesions (9/11) 93.2%] (13/17) AstraZeneca; Honoraria (self ), Advisory/Consultancy, Research grant/Funding maximum 56% 59% 45% (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self ), shrinkage rate of Advisory/Consultancy, Research grant/Funding (institution), Travel/ Accommodation/Expenses: Takeda; Honoraria (self ), Advisory/Consultancy, CNS target lesions S782 Journal of Thoracic Oncology Vol. 16 No. 4S

Legal entity responsible for the study: The authors. Methods: We evaluated the data of twenty-one ROS1 positive metastatic Funding: Has not received any funding. NSCLC patients treated with crizotinib retrospectively. The clinical, Disclosure: All authors have declared no conflicts of interest. pathological, and treatment data of the patients were recorded. We used SPSS version 27 for statistical analyses. Kaplan-Meier and Cox-regression analyses were used for survival analysis. – 155P Results: Median age was 56 (range, 23 79), and eleven (52.4%) of the Predictors of treatment response in ALK-positive metastatic patients were male. Thirteen (61.9%) of the patients were de-novo metastatic. The ratio of right-sided lung tumors was 81%. Before non-small cell lung cancer crizotinib, seven (33%) of the patients had received chemotherapy, and 33% of the patients palliative radiotherapy. Disease control ratio (partial I. Dogan1,M.Gürbüz2, N. Paksoy1, F. Ferhatoğlu1, S. Vatansever1, response-55.6%, stable response-27.8%) was 83.4%. Median progres- P. Saip1, A. Demirkazık2, A. Aydiner1 1Medical Oncology, Istanbul sion-free survival was 26.1 (95% CI, 8.1–44.1) months. Non-hemato- University Institute of Oncology, Istanbul, Turkey; 2Medical Oncology, logical toxicities were observed in 42.9% of the patients, and Ankara University Faculty of Medicine, Ankara, Turkey hematological toxicities in 19%. At a median follow of 17.2 (range, Background: ALK positivity is seen in approximately 5% of non-small 0.97–140.3) months, median overall survival was 35.2 (95% CI, 13.5– cell lung cancers (NSCLC), most commonly patients with younger age, 56.9) months. In univariate analysis, we found that age (p = 0.18), adenocarcinoma histology, and never smoking history. We can use gender (p = 0.72), smoking (p = 0.76), primary site of tumor (left or different types of ALK inhibitors such as alectinib, ceritinib, and right lung) (p = 0.37), de-novo metastasis (p = 0.16), history of crizotinib for treatment. In this study, we aimed to assess the predictors definitive radiotherapy (p = 0.58), brain metastasis (p = 0.06), adrenal of treatment response in ALK-positive metastatic NSCLC. gland metastasis (p = 0.09), receiving chemotherapy before crizotinib Methods: We evaluated the data of ALK-positive metastatic NSCLC (p = 0.08), and the number of metastatic sites (p = 0.06) were not patients treated with an ALK inhibitor retrospectively. The clinical, statistically significant prognostic factors for overall survival. The history pathological, and treatment data of the patients were recorded. We used of primary lung surgery (p = 0.03) and liver metastasis (p = 0.04) were SPSS 27 for statistical analyses. Response predictors were assessed by statistically significant. binary regression analysis. Besides, we evaluated the cut-off value of Conclusions: In the study, we determined the real-life outcomes of ALK positivity rate in tumor cells to respond to the treatment by ROC crizotinib. We found that crizotinib is effective and well-tolerated in analysis. patients with ROS1 positive metastatic NSCLC. Despite a small number of Results: Sixty-eight patients were included in the study. The median age patients, a history of primary lung surgery and no liver metastasis were was 55 (range, 30–81), and 36 (52.9%) of the patients were male. Sixty- positive prognostic factors. one (89.7%) of the patients had adenocarcinoma histology. De-novo Legal entity responsible for the study: The authors. metastatic disease ratio was 82.4%. At median follow up of 21 (range, 2– Funding: Has not received any funding. 172) months, median overall survival was 39.2 (95% CI, 26.6–51.6) Disclosure: All authors have declared no conflicts of interest. months. Thirty-five (51.5%) of the patients were treated with chemotherapy before ALK inhibitor. Patients had received alectinib (53%), crizotinib (44.1%), and ceritinib (2.9%) as ALK inhibitor. The response ratio (complete and partial) was 66.2%. In binary regression analysis, we found that gender (p = 0.045), ALK positivity ratio (p = 0.025), and the number of metastasis sites (p = 0.026) had predicted the response to ALK inhibitor. However, age (p = 0.948), the primary site of the tumor (left or right lung) (p = 0.359), tumor histology (adenocarcinoma or squamous) (p = 0.686), de-novo metastasis (p = 0.281), and type of ALK inhibitor (p = 0.561) were not predictive factors to the response. Also, we found the cut-off level of ALK positivity ratio in tumor cells for the response was 33% (p = 0.002, AUC:0.740, sensitivity 57.5%, specificity 78.3%). Conclusions: In this study, we determined the real-life efficiency of ALK inhibitors in patients with ALK-positive NSCLC. We found that the high ALK positivity ratio, female gender, and having under three metastatic sites were positive predictive factors of ALK inhibitors’ response. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

156P Outcomes of ROS1 positive metastatic lung cancer patients treated with crizotinib

I. Dogan, N. Khanmammadov, N. Paksoy, F. Ferhatoğlu, E. Aydin, S. Vatansever, P. Saip, A. Aydiner Medical Oncology, Istanbul University Institute of Oncology, Istanbul, Turkey Background: ROS1 is a driver oncogene that is detected in about 1–3% of patients with non-small cell lung cancer (NSCLC). We can use the drugs targeting ROS1 fusion in NSCLC. The purpose of the study was to evaluate the outcomes of patients with ROS1 positive metastatic NSCLC. April 2021 Abstracts S783

Table 157P 157P Tepotinib in patients (pts) with METexon 14 (METex14) Treatment-naïve Previously treated skipping NSCLC: Efficacy results from all pts enrolled in VISION Efficacy according to IRC (n = 69) (n = 83) cohort A Best objective response, n (%) 0 31 (44.9) 16 0 37 (44.6) 23 Complete response Partial (23.2) 13 (18.8) 9 (27.7) 13 (15.7) 10 A. Scherz1, H. Sakai2,X.Le3, E. Felip4, R. Veillon5, M.C. Garassino6, response Stable disease (13.0) (12.0) J. Raskin7, S. Viteri8, J. Mazieres9, A. Cortot10, E. Smit11, Progressive disease Not evaluable M. Thomas12, P. Conte13, M. Gottfried14, C. Britschgi15, R. Bruns16, 17 17 18 1 ORR, % (95% CI) 44.9 (32.9, 57.4) 44.6 (33.7, 55.9) G. Otto , A. Johne , P. Paik Department of Medical Oncology, Median DOR, months (95% CI) 10.8 (6.9, ne) 11.1 (9.5, 18.5) Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; 2Department of Thoracic Oncology, Saitama Cancer Center, Saitama, Japan; 3Department of Thoracic Head and Neck Medical Oncology, The Conclusions: Tepotinib showed robust and durable clinical activity University of Texas MD Anderson Cancer Center, Houston, TX, USA; across therapy lines, as expected when targeting an oncogenic driver. 4Department of Oncology, Vall d’Hebron Institute of Oncology (VHIO), Peripheral edema was the most common AE; most AEs were mild– Barcelona, Spain; 5CHU Bordeaux, Service des Maladies Respiratoires, moderate with few discontinuations. Bordeaux, France; 6Department of Medical Oncology, Fondazione IRCCS Clinical trial identification: NCT02864992. Istituto Nazionale dei Tumori, Milan, Italy; 7Department of Pulmonology Editorial acknowledgement: Medical writing assistance (funded by and Thoracic Oncology, Antwerp University Hospital (UZA), Edegem, Merck KGaA, Darmstadt, Germany) was provided by Syneos Health, Belgium; 8Dr Rosell Oncology Institute, Dexeus University Hospital, London, UK. QuironSalud Group, Barcelona, Spain; 9CHU de Toulouse, Institut Legal entity responsible for the study: Merck KGaA, Darmstadt, Universitaire du Cancer, Toulouse, France; 10Univ. Lille, CHU Lille, CNRS, Germany. Inserm, Institut Pasteur de Lille, Lille, France; 11Department of Thoracic Funding: Merck KGaA, Darmstadt, Germany. Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands; 12 Disclosure: A. Scherz: Advisory/Consultancy: AstraZeneca; Advisory/ Thoraxklinik, University Heidelberg and Translational Lung Research Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Takeda; Advisory/ Center Heidelberg (TLRC-H), The German Center for Lung Research (DZL), Consultancy: MSD Merck Sharp & Dohme. H. Sakai: Speaker Bureau/Expert Heidelberg, Germany; 13Department of Surgery, Oncology and testimony: BMS; Speaker Bureau/Expert testimony: Ono Pharmaceutical; Speaker Gastroenterology, University of Padova and Oncologia Medica 2, Istituto Bureau/Expert testimony: MSD K.K.; Speaker Bureau/Expert testimony: 14 AstraZeneca; Speaker Bureau/Expert testimony: Chugai Pharmaceutical; Speaker Oncologico Veneto, I.R.C.C.S., Padua, Italy; Meir Medical Center, Bureau/Expert testimony: Taiho Pharmaceutical; Speaker Bureau/Expert testi- 15 TchernichovskySt 59,Kefar Sava,Israel; Department ofMedicalOncology mony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Merck KGaA. and Hematology, Comprehensive Cancer Center Zurich, University Hospital X. Le: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/ Zurich, Zurich, Switzerland; 16Department of Biostatistics, Merck KGaA, Funding (self ): Eli Lilly; Advisory/Consultancy: EMD Serono; Research grant/ 17 Funding (self ): Boehringer Ingelheim. E. Felip: Advisory/Consultancy, Speaker Darmstadt, Germany; Global Clinical Development, Merck KGaA, Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert 18 Darmstadt, Germany; Thoracic Oncology Service, Memorial Sloan- testimony: Roche; Advisory/Consultancy: Boehringer Ingelheim; Advisory/ Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/ Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/ Background: In the primary analysis of the phase II VISION study, Consultancy: Guardant Health; Advisory/Consultancy, Speaker Bureau/Expert tepotinib demonstrated durable efficacy and a tolerable safety profile in testimony: Novartis; Advisory/Consultancy: Sharp & Dohme; Advisory/ Consultancy: Janssen; Advisory/Consultancy: Samsung; Speaker Bureau/Expert pts with METex14 skipping NSCLC, as identified by liquid and/or tissue testimony: Takeda; Speaker Bureau/Expert testimony: Lilly; Speaker Bureau/ biopsy. Here, we report updated efficacy outcomes in all pts across Expert testimony: Merck Sharp & Dohme; Speaker Bureau/Expert testimony: treatment lines. Medscape; Speaker Bureau/Expert testimony: prIME Oncology; Speaker Bureau/ ́ Methods: Pts with advanced, EGFR/ALK wild-type, METex14 skipping Expert testimony: Touchtime; Research grant/Funding (self ): Fundacion Merck Salud; Research grant/Funding (self ): Grant for Oncology Innovation (GOI); NSCLC received oral tepotinib 500 mg once daily. All pts who received Officer/Board of Directors: Grifols. R. Veillon: Advisory/Consultancy, Speaker tepotinib in Cohorts A (enrollment complete) + C (ongoing) were Bureau/Expert testimony: MSD; Advisory/Consultancy: Pfizer; Advisory/ assessed for safety; pts in Cohort A were assessed for efficacy. Primary Consultancy: Novartis; Speaker Bureau/Expert testimony, Research grant/ endpoint was objective response (OR) assessed by independent review Funding (self ): BMS; Speaker Bureau/Expert testimony, Research grant/Funding (self ): Roche; Research grant/Funding (self ): Takeda; Research grant/Funding committee (IRC). Secondary endpoints included duration of response (self ): AbbVie; Research grant/Funding (self ): Merck. M.C. Garassino: Advisory/ (DOR) and safety. Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Novartis; Advisory/ Results: 152 pts were enrolled; pts were elderly (median 73.1 years), Consultancy: Pfizer; Advisory/Consultancy: Seattle Genetics; Advisory/ half were male (52.0%), half had smoking history (52.0%), and most had Consultancy: Daiichi Sankyo; Advisory/Consultancy: Sanofi; Speaker Bureau/ ≥ Expert testimony: Otsuka Pharma; Speaker Bureau/Expert testimony: Incyte; adenocarcinoma (86.2%). In pts with 1 (n = 49) or 2 (n = 34) prior Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/ treatments, best OR across all prior therapies were two CRs (2.4%) and Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, 24 PRs (28.9%) with a median longest DOR of 7 months (range 1–17). As Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker of July 1, 2020, objective response rate (ORR) was 44.7% (95% CI: 36.7, Bureau/Expert testimony: Celgene; Honoraria (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy, Speaker 53.0), and median DOR was 11.1 months (95% CI: 8.4, 18.5). Efficacy Bureau/Expert testimony, Steering committee: MSD; Advisory/Consultancy, was consistent between treatment-naïve (n = 69) and previously treated Speaker Bureau/Expert testimony: AstraZeneca. J. Raskin: Advisory/ (n = 83) pts (Table). Pts with brain mets (n = 23) had a comparable ORR Consultancy: Pfizer; Advisory/Consultancy: Lilly; Speaker Bureau/Expert testi- of 47.8% (95% CI: 26.8, 69.4) and a median DOR of 9.5 months (95% CI: mony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: BMS; Travel/ ≥ Accommodation/Expenses: Roche. S. Viteri: Advisory/Consultancy: AbbVie; 5.5, not estimable). Safety was assessed in 255 pts. Grade 3 treatment- Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/ related adverse events (TRAEs) were reported in 64 pts (25.1%). 27 pts Accommodation/Expenses: BMS; Advisory/Consultancy, Speaker Bureau/Expert (10.6%) discontinued due to TRAEs. The most common TRAE was testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, peripheral edema (138 pts [54.1%] all grades, 19 pts [7.5%] Grade ≥3), Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: OSE Pharma; Travel/Accommodation/Expenses: Merck; Travel/ which led to treatment discontinuation in 9 pts (3.5%). Accommodation/Expenses: Merck Serono; Travel/Accommodation/Expenses: Puma Biotechnology; Travel/Accommodation/Expenses: Janssen Cilag. J. Mazieres: Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Advisory/ Consultancy: Pfizer; Advisory/Consultancy: Novartis. A. Cortot: Research grant/ Funding (self ): Merck KGaA; Honoraria (self ), Advisory/Consultancy, Research S784 Journal of Thoracic Oncology Vol. 16 No. 4S grant/Funding (self ), Travel/Accommodation/Expenses: Novartis; Honoraria publications, describing 17 (eight observational; nine non-comparative (self ), Travel/Accommodation/Expenses: MSD; Honoraria (self ), Advisory/ interventional) studies reported clinical outcomes. Across these studies, Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self ), – Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/ the average median age was 72 years (range: 67 77), 51% patients were Consultancy, Travel/Accommodation/Expenses: Takeda; Honoraria (self ), male (range: 32–69%), and 79% of patients had adenocarcinoma (range: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; 57–93%). 17 publications reported an objective response rate (ORR) Honoraria (self ), Advisory/Consultancy: BMS. E. Smit: Advisory/Consultancy: according to RECIST criteria from 11 studies (Table). Lilly; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Roche/ Table 158P: Range of ORR reported in identified studies Genentech; Advisory/Consultancy, Research grant/Funding (institution): Bristol- Myers Squibb; Advisory/Consultancy: Merck KGaA; Advisory/Consultancy: MSD Second-line or Oncology; Advisory/Consultancy: Takeda; Advisory/Consultancy, Research grant/ Any line First-line greater Funding (institution): Bayer; Advisory/Consultancy: Regeneron; Advisory/ MET TKIs 43% (n = 70) to 44% (n = 43) to 41% (n = 69) to Consultancy: Novartis; Advisory/Consultancy: Daiichi Sankyo; Advisory/ 75% (n = 4) (three 68% (n = 28) (three 57% (n = 56) (two Consultancy: Seattle Genetics. M. Thomas: Honoraria (self ), Research grant/ Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self ), studies) studies) studies) Travel/Accommodation/Expenses: MSD; Honoraria (self ), Research grant/ MET targeted 25% (n = 12) (one -- Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria antibody study) (self ), Travel/Accommodation/Expenses: Novartis; Honoraria (self ), Research Multi-kinase 32% (n = 69) to 60% (n = 5) (one 20% (n = 10) (one grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria inhibitors 40% (n = 25) (two study) study) (self ), Research grant/Funding (institution), Travel/Accommodation/Expenses: studies) Takeda; Honoraria (self ), Travel/Accommodation/Expenses: Lilly; Honoraria Chemotherapy - 23% (n = 14) to - (self ), Travel/Accommodation/Expenses: Chugai; Honoraria (self ), Travel/ 29% (n = 17) (two Accommodation/Expenses: Celgene; Honoraria (self ), Travel/Accommodation/ Expenses: Boehringer; Honoraria (self ), Travel/Accommodation/Expenses: Pfizer. studies) P. Conte: Speaker Bureau/Expert testimony, Research grant/Funding (self ), Immunotherapy 17% (n = 147) to -- Travel/Accommodation/Expenses: Novartis; Speaker Bureau/Expert testimony, 33% (n = 6) (two Research grant/Funding (self ): Roche; Research grant/Funding (self ): Merck studies) KGaA; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Celgene; Travel/ Accommodation/Expenses: Tesaro. M. Gottfried: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/ Conclusions: Where prevalence was reported, METex14 skipping was Consultancy: Roche/Genentech; Advisory/Consultancy: BMS; Advisory/ rare. For patients with METex14 skipping NSCLC, MET TKIs generally Consultancy: MSD Oncology; Advisory/Consultancy: Takeda; Advisory/ appeared to result in better clinical outcomes than regimens that did not Consultancy: AbbVie; Advisory/Consultancy: Novartis. C. Britschgi: Advisory/ Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/ include MET TKIs highlighting the importance of mutation testing. Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy, However, all reported clinical outcomes were derived from non- Travel/Accommodation/Expenses: Takeda; Advisory/Consultancy: Janssen- comparative interventional or observational studies and further Cilag; Advisory/Consultancy: Boehringer Ingelheim. R. Bruns: Shareholder/ comparisons with more updated data may be needed to determine Stockholder/Stock options, Full/Part-time employment: Merck KGaA. G. Otto: Full/Part-time employment: Merck KGaA. A. Johne: Full/Part-time employment: relative effectiveness. Merck KGaA. P. Paik: Advisory/Consultancy: AbbVie; Advisory/Consultancy: BMS; Editorial acknowledgement: Medical writing assistance (funded by Advisory/Consultancy: Calithera; Advisory/Consultancy, Research grant/Funding Merck KGaA, Darmstadt, Germany) was provided by Syneos Health, (institution): Celgene; Advisory/Consultancy: Lilly; Advisory/Consultancy: London, UK. Takeda; Research grant/Funding (institution): EMD Serono. Legal entity responsible for the study: Merck KGaA. Funding: Merck KGaA. Disclosure: A. Cortot: Research grant/Funding (self ): Merck KGaA; Honoraria 158P (self ), Advisory/Consultancy, Research grant/Funding (self ), Travel/ Prevalence and clinical outcomes of METexon 14 (METex14) Accommodation/Expenses: Novartis; Honoraria (self ), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self ), Advisory/ skipping in patients with advanced NSCLC: A systematic Consultancy: BMS; Honoraria (self ), Travel/Accommodation/Expenses: MSD; literature review Honoraria (self ), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self ), Advisory/Consultancy, Travel/Accommodation/ 1 2 3 3 3 4 Expenses: Roche; Honoraria (self ), Advisory/Consultancy, Travel/ A. Cortot , J. Mazieres , A. Gezin , A. Garcia , B. Heeg , B. Pfeiffer , Accommodation/Expenses: Takeda. J. Mazieres: Advisory/Consultancy: Roche; 4 1 H. Vioix Thoracic Oncology Department, Universite de Lille, Lille, Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BMS; Advisory/ France; 2Thoracic Oncology Department, Centre Hospitalier Universitaire Consultancy: MSD; Advisory/Consultancy: Pfizer; Advisory/Consultancy: de Toulouse - Hopital Larrey, Toulouse, France; 3Ingress-Health, Novartis. B. Pfeiffer: Full/Part-time employment: Merck KGaA. H. Vioix: Full/ 4 Part-time employment: Merck KGaA. All other authors have declared no conflicts Rotterdam, Netherlands; Merck KGaA, Darmstadt, Germany of interest. Background: A systematic literature review was conducted to understand the prevalence and association between METex14 skipping, a rare primary oncogenic driver in NSCLC, and clinical outcomes. 159P Methods: We searched EMBASE, PubMed and selected conferences Clinical characteristics of patients with advanced NSCLC and following National Institute for Health and Care Excellence guidelines; METexon 14 (METex14) skipping: A systematic literature two independent reviewers assessed the eligibility based on predefined review criteria. Search terms identified interventional and non-interventional studies including prevalence and clinical outcomes in METex14 skipping J. Mazieres1, A. Cortot2, A. Gezin3, A. Garcia3, B. Heeg3, B. Pfeiffer4, NSCLC. H. Vioix4 1Thoracic Oncology Department, Centre Hospitalier Results: A total of 753 abstracts were screened, and 130 eligible Universitaire de Toulouse - Hopital Larrey, Toulouse, France; 2Thoracic publications were identified. 108 publications (184,699 patients) Oncology Department, Universite de Lille, Lille, France; 3Ingress-Health, reported prevalence of METex14 skipping in NSCLC, which ranged Rotterdam, Netherlands; 4Merck KGaA, Darmstadt, Germany from 0.6–6.6% (Asia), 1.4–3.3% (Europe) and 2.3–5.1% (North America). The assay type, number of patients screened, study setting Background: METex14 skipping is a rare primary oncogenic driver in (single or multiple institutions), and whether routine screening for MET non-small cell lung cancer (NSCLC). A systematic literature review was alterations was carried out could affect the reported prevalence. 25 conducted to fully evaluate the characteristics of patients with advanced NSCLC with METex14 skipping. April 2021 Abstracts S785

Methods: We searched EMBASE, PubMed and selected conferences Methods: This is an ongoing, non-interventional, descriptive cohort following the National Institute for Health and Care Excellence guide- study using data from the ConcertAI electronic medical record database lines; two independent reviewers assessed the eligibility of articles derived from US community oncology centers and linked with ASCO based on predefined criteria. Search terms identified interventional and CancerLinQ data. Pts had advanced (stage IIIB–IV) NSCLC harboring non-interventional studies, of any design, reporting outcomes in patients METex14 skipping. Period of this analysis was Jan 1, 2004 – Mar 31, with METex14 skipping NSCLC. 2020. Baseline medical history was described prior to/at advanced Results: A total of 753 abstracts were screened and 130 eligible diagnosis, and effectiveness outcomes after systemic therapy initiation. publications were identified. 37 publications reported the character- Results: The table shows characteristics and treatment for 54 eligible istics of patients (n = 1,211) with METex14 skipping NSCLC. Data from pts of 5,339 screened. Other established oncogenic driver mutations 28 publications including 1,108 patients showed a median age of 72.3 were uncommon in pts positive for METex14 skipping. 51 pts received years (interquartile range [IQR] of reported medians: 67.1–74.8; range: systemic anticancer therapy for advanced NSCLC. Treatment patterns 64.0–80.5). 45% of patients were male (IQR: 35–61%; range: 0%–88%) were heterogeneous across therapy lines and included available and and 55% of patients were female (IQR: 39–65%; range: 12–100%) (data experimental treatments (immune checkpoint inhibitor [ICI] therapy; from 31 publications/1,086 patients). Patients were more commonly MET inhibitors [crizotinib, cabozantinib, and glesatinib]). The objective ‘ever smokers’ (55% [IQR: 31–64%; range: 0–80%]) than ‘never response rates (ORRs) were 35.3% for first-line (1L, n = 51), 18.5% for smokers’ (40% [IQR: 33–53%; range: 20–78%, excluding outliers]) second-line (2L, n = 27), and 7.1% for third-line (3L, n = 14). Median (data from 21 publications/809 patients). The most commonly reported progression-free survival (mPFS) was 3.1 months (95% confidence histologies were adenocarcinoma (79% [IQR: 66–84%; range: 50–100%, interval [CI]: 2.3, 5.0) for 1L, 4.6 months (95% CI: 1.6, 5.7) for 2L, and 4.1 excluding outliers]) from 29 publications (950 patients), pulmonary months (0.6, 35.9) for 3L. The median overall survival from the start of sarcomatoid carcinoma (10% [IQR: 0–33%; range: 0–39%, excluding 1L was 10.4 months. For pts who received ICI therapy in 1L (n = 21), outliers]) from 18 publications (757 patients), and squamous cell ORR was 33.3% (14.6, 57.0) and mPFS was 4.1 months (1.5, 8.1); in 2L carcinoma (8% [IQR: 0–17%; range: 0–22%, excluding outliers]) from (n = 10), ORR was 20% (2.5, 55.6) and mPFS was 4.1 months (1.5, 8.1). 19 publications (782 patients). Conclusions: Findings from this review help to better characterize this Table 160P rare patient population, confirming that patients with METex14 skipping NSCLC are typically elderly and that METex14 skipping is found across Characteristics METex14 (n = 54) histologies. This underscores the importance of testing all patients with Age, median (Q1–Q3), years 75.5 (69.3–80.4) NSCLC for METex14 skipping alterations in order to receive targeted Male, n (%) 21 (38.9) treatment. Prior/current smokers, n (%) 35 (64.8) Editorial acknowledgement: Medical writing assistance (funded by Stage IV, n (%) 49 (90.7) Merck KGaA, Darmstadt, Germany) was provided by Syneos Health, Histology, n (%) Adenocarcinoma 37 (68.5) 10 (18.5) 7 (13) London, UK. Squamous cell carcinoma Other Legal entity responsible for the study: Merck KGaA. Brain metastases, n (%) 9 (16.4) Funding: Merck KGaA. ECOG PS, n (%) 0–12–3 Unknown 23 (42.6) 11 (20.4) 20 (37.0) PD-L1 expression*/tested, n (% of 31/49 (63.3) 9 (29.0) 20 (40.8) 2 Disclosure: J. Mazieres: Advisory/Consultancy: Roche; Advisory/Consultancy: – BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; pts tested) 1 50% >50% Unknown (4.1) Advisory/Consultancy: Pfizer; Advisory/Consultancy: Novartis. A. Cortot: Systemic therapy**, n 1L: 51, 2L: 27, 3L: 14 Research grant/Funding (self ): Merck KGaA; Honoraria (self ), Advisory/ ICI monotherapy/combination 1L: 21, 2L: 10, 3L: 6 Consultancy, Research grant/Funding (self ), Travel/Accommodation/Expenses: Chemotherapy 1L: 20, 2L: 9, 3L: 4 Novartis; Honoraria (self ), Advisory/Consultancy, Travel/Accommodation/ MET inhibitors 1L: 10, 2L: 8, 3L: 4 Expenses: AstraZeneca; Honoraria (self ), Advisory/Consultancy, Travel/ Accommodation/Expenses: BMS; Honoraria (self ), Travel/Accommodation/ *Expression of tumor proportion score (by immunohistochemistry). **5 pts Expenses: MSD; Honoraria (self ), Advisory/Consultancy, Travel/ participated in a clinical trial. Accommodation/Expenses: Pfizer; Honoraria (self ), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self ), Advisory/ Consultancy, Travel/Accommodation/Expenses: Takeda. B. Pfeiffer: Full/Part- Conclusions: Pts were generally at advanced age, were frequent time employment: Merck KGaA. H. Vioix: Full/Part-time employment: Merck KGaA. smokers and had high-PD-L1 expression. Findings from this study help All other authors have declared no conflicts of interest. better characterize this rare population; treatment patterns and effectiveness outcomes underline the high unmet medical need. Editorial acknowledgement: Editorial assistance (funded by Merck 160P KGaA, Darmstadt, Germany) was provided by Suzanne Patel on behalf of Non-interventional cohort study on patients (pts) with Syneos Health, London, UK. advanced non-small cell lung cancer (NSCLC) harboring MET Legal entity responsible for the study: Merck KGaA. exon 14 (METex14) skipping in the US Funding: Merck KGaA. Disclosure: A. Ryder: Advisory/Consultancy: ConcertAI. D. Oksen: Full/Part- 1 2 3 2 3 2 time employment: Merck KGaA. E. Boutmy: Full/Part-time employment: Merck A. Ryder , D. Oksen , A. Vlahiotis , E. Boutmy , L.A. Dietz , C. Stroh , KGaA. C. Stroh: Full/Part-time employment: Merck KGaA. A. Johne: Full/Part-time 2 3 1 A. Johne , M. Walker West Cancer Center and Research Institute, employment: Merck KGaA. All other authors have declared no conflicts of interest. Memphis, TN, USA; 2Merck KGaA, Darmstradt, Germany; 3ConcertAI, Memphis, TN, USA

Background: METex14 skipping is a rare oncogenic driver in NSCLC (∼3%); clinical characteristics and effectiveness outcomes are not well- characterized. S786 Journal of Thoracic Oncology Vol. 16 No. 4S

161P 162P Real-world large-scale study of KRAS fusions in Chinese non- Long-term efficacy and genomic characteristics of patients small cell lung cancer patients: A multicenter study (Yangtze with TRK fusion lung cancer treated with larotrectinib River Delta Lung Cancer Cooperation Group-002) V. Moreno Garcia1, J. Lin2, J. Patel3, U. Lassen4, B. Solomon5, D. Wang1, W-X. Wang2,C.Xu3, J-Y. Chen1, Y-C. Zhu4, H. Wang5, L. Rosen6, S. Leyvraz7, D.S.W. Tan8, J.A. Reeves9, G. Beckmann10, G-H. Yu6, H-J. Feng7, B-B. Song8, L-P. Wang9, W. Zhuang10, M-Y. Fang2, M. Rudolph10, J. Wierzbinska10, L. Dima11, N. Brega9, S. Kummar12, Q. Wang11, G-S. Wang12, Y. Song1,S.Lu13 1Respiratory Medicine, Jinling A. Drilon13 1START MADRID-FJD, Hospital Fundacioń Jimeneź Dıaz,́ Hospital, Nanjing University School of Medicine, Nanjing, China; 2Medical Madrid, Spain; 2Department of Medicine, Massachusetts General Hospital Oncology, Chinese Academy of Sciences University Cancer Hospital and Harvard Medical School, Boston, MA, USA; 3Northwestern University, (Zhejiang Cancer Hospital), Hangzhou, China; 3Pathology Department, Chicago, IL, USA; 4Department of Oncology, Rigshospitalet, Copenhagen, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Denmark; 5Avera Cancer Institute, Sioux Falls, SD, USA; 6UCLA Division of Fuzhou, China; 4Thoracic Disease Center, Zhejiang Rongjun Hospital, Hematology-Oncology, Santa Monica, CA, USA; 7Charité– Jiaxing, China; 5Lung Cancer, The Fifth Medical Center, General of PLA, Universitätsmedizin Berlin, Berlin, Germany; 8Division of Medical Beijing, China; 6Radiotherapy, Zhebei Mingzhou Hospital, Huzhou, China; Oncology, National Cancer Centre Singapore, Singapore; 9Bayer 7Medical Oncology, Shanxi Academy of Medical Sciences, Shanxi Bethune HealthCare Pharmaceuticals, Whippany, NJ, USA; 10Bayer AG Hospital, Taiyuan, China; 8Medical Oncology, The Affiliated Hospital of Pharmaceuticals, Berlin, Germany; 11Bayer HealthCare Pharmaceuticals, Jiaxing University, Jiaxing, China; 9Medical Oncology, Baotou Cancer Inc., Basel, Switzerland; 12Oregon Health & Science University, Portland, Hospital, Baotou, China; 10Medical Oncology, Fujian Cancer Hospital and OR, USA; 13Memorial Sloan Kettering Cancer Center and Weill Cornell Fujian Medical University Cancer Hospital, Fuzhou, China; 11Respiratory Medical College, New York, NY, USA Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Background: NTRK gene fusions are known oncogenic drivers. Nanjing, China; 12Respiratory Medicine, Xinqiao Hospital of Third Military Larotrectinib is a highly selective, CNS-active TRK inhibitor approved Medical University, Chongqing, China; 13Shanghai Lung Cancer Center, to treat patients (pts) with TRK fusion cancer, with an objective response Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China rate (ORR) of 78% and median progression-free survival (PFS) of 36.8 Background: KRAS gene mutations were well known as a key driver of months across multiple cancers (McDermott et al, ESMO 2020). We advanced non-small cell lung cancer (NSCLC), however, KRAS fusion report long-term efficacy outcomes and genomic characteristics, gene were rare and unfamiliar. With the advances in detection including circulating tumour (ct) DNA, of pts with TRK fusion lung techniques, such as next generation sequencing (NGS), more and more cancer treated with larotrectinib. rare KRAS fusions had been identified. The aim of this study was to Methods: Pts with lung cancer harbouring an NTRK gene fusion evaluate the prevalence of KRAS fusions in Chinese NSCLC populations, enrolled in two clinical trials were pooled. Larotrectinib 100 mg BID was which had not been reported earlier, and to describe immunotherapy in administered. Response was investigator-assessed per RECIST v1.1. Chinese KRAS fusion NSCLC populations. Genomic data were collected from available sources (molecular Methods: A multicenter study in China was initiated from February pathology reports, ctDNA analysis). The data cut-off was 15 July 2019. 2014, and NSCLC patients have been enrolled as of December 2019. To Results: A total of 14 pts with TRK fusion lung cancer were enrolled. 7 pts determine the frequency of the KRAS fusions in NSCLC, we analyzed data had baseline CNS metastases. Pts were heavily pre-treated with a median from 3046 clinical NSCLC cases, each of which had results from next- of 3 prior therapies (range 0–5). ORR was 71% (95% CI 42–92). ORR in generation sequencing (NGS), analogous to the index patient. pts with CNS metastases was 57% (95% CI 18–90). Median duration of Results: Of this entire cohort, 3 (0.10%) patients were identified with a response (DoR) was not estimable (NE; 95% CI 5.6–NE), with a 12-month KRAS fusion, including MRPS35-KRAS (1), TMBIM4-KRAS (1) and DoR rate of 88%. Median PFS was also NE (95% CI 7.2–NE), with a 12- C12orf4-KRAS (1). For treatments, 33.33% (1/3) patients chose month PFS rate of 69%. Median overall survival (OS) was NE (95% CI Sintilimab combined chemotherapy, other two patients chose chemo- 17.2–NE), with a 12-month OS rate of 91%. Treatment duration ranged therapy or chemoradiotherapy, and the case example of advanced KRAS from 2.1 to 39.6+ months. Adverse events were mainly Grade 1–2. fusion driven NSCLC patients responding to immunotherapy were Oncogenic alterations commonly detected in lung cancer such as EGFR, actively being sought through our database. KRAS, BRAF and ALK were not detected at baseline in these pts. At data Conclusions: KRAS fusions occur in a subset of patients with NSCLC. cut-off, 4 pts had progressed, 3 of whom had on-target NTRK1 mutations: Patients with advanced KRAS fusion NSCLC may have a relatively good 1 solvent front (SF; G595R) and xDFG (G667S), 1 SF (G595R) and gate outcome of immunotherapy, and such patients should be considered for keeper (GK, F589L), 1 GK (F589L). In addition, the first pt had BRAF, MET clinical trials featuring immunotherapy. Moreover, NGS can provide and EGFR amplification and the last a KRAS G12D mutation. information for immunotherapy. For NSCLC patients to benefit from Conclusions: Larotrectinib demonstrated durable responses, extended more personalized cancer treatment, clinical therapy should improve survival and a favourable safety profile in pts with TRK fusion lung with clinical diagnostics through multi-gene assays to determine the cancer. Common oncogenic drivers were not found at baseline, actual clinical benefits. supporting NTRK gene fusions as the primary oncogenic driver. Legal entity responsible for the study: Chunwei Xu. Progression was correlated to known resistance mechanisms. These Funding: Has not received any funding. data highlight the importance of NTRK gene fusion testing in pts with Disclosure: All authors have declared no conflicts of interest. lung cancer. Clinical trial identification: NCT02122913 NCT02576431. Editorial acknowledgement: Editorial assistance was provided by Farzana Miah, MSc, and Annabel Ola, MSc (Scion, London UK), funded by Bayer Healthcare Pharmaceuticals, Inc. Legal entity responsible for the study: Bayer Pharmaceuticals, Inc. and Loxo Oncology, a subsidiary of Lilly. Funding: Bayer Pharmaceuticals, Inc, and Loxo Oncology, a subsidiary of Lilly. Disclosure: V. Moreno Garcia: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy: April 2021 Abstracts S787

Pieris; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/ Accommodation/Expenses: BMS; Advisory/Consultancy: Janssen; Travel/ Accommodation/Expenses: Regeneron/Sanofi; Speaker Bureau/Expert testi- 163P mony: Nanobiotix; Research grant/Funding (institution), Educational grant: Circulating tumour (ct) DNA next generation sequencing Medscape/Bayer. J. Lin: Honoraria (self ): Pfizer; Honoraria (self ): Genentech; (NGS) in UK advanced non-small cell lung cancer (aNSCLC) Honoraria (self ): C4 Therapeutics; Honoraria (self ): Nuvalent; Honoraria (self ): Blueprint Medicines; Honoraria (self ): Turning Point Therapeutics; Honoraria patients (pts) (self ): Hengrui Therapeutics; Honoraria (self ): Neon Therapeutics; Honoraria (self ): Relay Therapeutics; Honoraria (self ): Novartis; Honoraria (self ): Bayer; W. Cui1, C. Milner-Watts1, H. Lyons1, N. Yousaf1, A.R. Minchom1, Honoraria (self ): Elevation Oncology; Honoraria (self ): Roche. J. Patel: Advisory/ J. Bhosle1, M. Davidson1, S. Scott2, I. Faull2, R.J. Nagy2, Consultancy: ARIAD; Advisory/Consultancy: AbbVie; Advisory/Consultancy: ’ 3 4 1 AstraZeneca; Advisory/Consultancy: Takeda Science Foundation. U. Lassen: M.E.R. O Brien , S. Popat Department of Medicine (Lung), The Royal 2 Advisory/Consultancy: Bayer. B. Solomon: Travel/Accommodation/Expenses: Marsden Hospital - NHS Foundation Trust, London, UK; Guardant Health AstraZeneca. L. Rosen: Research grant/Funding (institution): Bayer. S. Leyvraz: Inc., Redwood City, CA, USA; 3The Royal Marsden Hospital - NHS Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer. D.S.W. Tan: Foundation Trust, Imperial College London, London, UK; 4The Royal Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Merck; Advisory/Consultancy: Loxo; Marsden Hospital - NHS Foundation Trust, Imperial College London, Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Institute of Cancer Research, London, UK Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/ Expenses: Roche; Honoraria (institution), Advisory/Consultancy, Travel/ Background: Identification of targetable genomic alterations is Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: necessary for NSCLC treatment decision-making and the clinical utility Boehringer Ingelheim; Honoraria (institution): BMS; Honoraria (institution): of ctDNA NGS is well-established. Here we report our real-world Takeda; Research grant/Funding (institution): GSK. J.A. Reeves: Full/Part-time employment: Bayer. G. Beckmann: Full/Part-time employment: Bayer. M. Rudolph: experience utilising ctDNA NGS in 184 newly diagnosed or relapsed Full/Part-time employment: Bayer. J. Wierzbinska: Full/Part-time employment: aNSCLC pts. Bayer. L. Dima: Full/Part-time employment: Bayer. N. Brega: Full/Part-time Methods: Guardant360™ (G360) ctDNA NGS was performed in employment: Bayer. S. Kummar: Honoraria (institution), Advisory/Consultancy, consecutive pts with aNSCLC between Oct 19-Dec 20 at Royal Travel/Accommodation/Expenses: Bayer. A. Drilon: Honoraria (institution), Advisory/Consultancy: Ignyta/Genentech/Roche; Honoraria (institution), Marsden Hospital. AMP/ASCO/CAP tier guidelines were used. Tier 1 Advisory/Consultancy: Loxo/Bayer/Lilly; Honoraria (institution), Advisory/ variants detected on G360 are described. G360 results were compared to Consultancy: Takeda/Ariad/Millenium; Honoraria (institution), Advisory/ tissue molecular test results. Consultancy: TP Therapeutics; Honoraria (institution), Advisory/Consultancy: Results: 91% (167/184) of pts had at least one genomic variant AstraZeneca; Honoraria (institution), Advisory/Consultancy, Research grant/ Funding (institution): Pfizer; Honoraria (institution), Advisory/Consultancy: identified via G360. 80 pts (43%) had a tier 1 variant identified by G360. Blueprint Medicines; Honoraria (institution), Advisory/Consultancy: Helsinn; Of these, 23/80 (29%) were not identified in tissue, including targetable Honoraria (institution), Advisory/Consultancy: Beigene; Honoraria (institution), alterations in EGFR, KRAS, ERBB2, BRAF, MET. 34% (63/184) of tissue Advisory/Consultancy: BergenBio; Honoraria (institution), Advisory/ molecular tests detected at least one variant, 92 (50%) detected no Consultancy: Hengrui Therapeutics; Honoraria (institution), Advisory/ Consultancy, Research grant/Funding (institution): Exelixis; Honoraria (institu- variants, 11 (6%) failed (insufficient tissue), and 18 (10%) pts did not tion), Advisory/Consultancy: Tyra Biosciences; Honoraria (institution), Advisory/ have tissue results available. 48 (26%) tissue molecular tests identified a Consultancy: Verastem; Honoraria (institution), Advisory/Consultancy: MORE tier 1 variant. 5 tissue tier 1 variants were not detected on G360: EGFR Health; Honoraria (institution), Advisory/Consultancy: AbbVie; Honoraria (insti- L858R (1), EGFR T790M (2), MET ex 14 skipping (2). Median time from tution), Advisory/Consultancy: 14ner/Elevation Oncology; Honoraria (institution), Advisory/Consultancy: Remedica Ltd; Honoraria (institution), Advisory/ request to report was shorter for G360 compared to standard tissue Consultancy: ArcherDX; Honoraria (institution), Advisory/Consultancy: molecular tests (9 vs 24 days, p = 0.002). Monopteros; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: EMD Serono; Honoraria (institution), Table 163P: Pt characteristics Advisory/Consultancy: Melendi; Honoraria (institution), Advisory/Consultancy: Liberum; Honoraria (institution), Advisory/Consultancy: Repare RX; Honoraria Tier 1 variant on No tier 1 variant on (institution), Advisory/Consultancy: Elevation Oncology; Research grant/Funding G360 N (%) N = 80 G360 N (%) N = 104 (institution): GlaxoSmithKlein; Research grant/Funding (institution): Teva; (43%) (57%) Research grant/Funding (institution): Taiho; Research grant/Funding (institution): PharmaMar; Research grant/Funding (self ): Foundation Medicine; Age Licensing/Royalties: Wolters Kluwer; Travel/Accommodation/Expenses, Food Median (range) 67 (39–89) 71 (33–97) and beverage: Merck; Travel/Accommodation/Expenses, Food and beverage: Sex Puma; Travel/Accommodation/Expenses, Food and beverage: Merus; Travel/ Male 24 (37) 78 (66) Accommodation/Expenses, Food and beverage: Boehringer Ingelheim; Honoraria Female 41 (63) 41 (34) (self ), CME: Medscape; Honoraria (self ), CME: OncLive; Honoraria (self ), CME: PeerVoice; Honoraria (self ), CME: Physicians Education Resources; Honoraria Smoking (self ), CME: Targeted Oncology; Research grant/Funding (institution): Axis; Never 21 (32) 12 (10) Research grant/Funding (institution): Peerview Institute; Research grant/Funding Ex/current 43 (66) 106 (90) (institution): Paradigm Medical Communications; Research grant/Funding (insti- NA 1 (2) 1 (<1) tution): WebMD; Research grant/Funding (institution): MJH Life Sciences; Median pack years 7.5 (0–100) 30 (0–150) Research grant/Funding (institution): Med Learning; Research grant/Funding Ethnicity (institution): Imedex; Research grant/Funding (institution): Answers in CME; White 54 (83) 109 (92) Research grant/Funding (institution): Medscape; Research grant/Funding (insti- Other 11 (17) 10 (8) tution): Clinical Care Options. Histology Adenocarcinoma 62 (95) 76 (64) Squamous cell 0 35 (29) Other 3 (5) 8 (7) G360 tier 1 variants detected EGFR ins 20 4 EGFR del 18 1 EGFR L861Q 1 EGFR G719A 1 EGFR del 19 10 EGFR del 19 + T790M 3 EGFR del 19 + T790M + C797S 4 EGFR del 19 + MET amplification 1

(continued) S788 Journal of Thoracic Oncology Vol. 16 No. 4S

Table 163P: (Continued) SafeSEQ, an orthogonal NGS-based LB assay. TAT was calculated as number of days from specimen receipt to results. Tier 1 variant on No tier 1 variant on Results: The mean TAT of OncoBEAM results for 40 samples G360 N (%) N = 80 G360 N (%) N = 104 prospectively tested was 4.25 ± 0.98 days (95% CI: 3.94–4.56), with (43%) (57%) the most and least rapid results delivered within 3 and 6 days, EGFR L858R 7 respectively. For the same 40 patients, the mean TAT of tissue-based EGFR L858R + T790M 1 genotyping was 12.13 ± 4.42 days (95% CI: 10.68–13.59). Of 54 (29%) EML4-ALK 3 ctDNA positive patients in the full cohort (n = 187), EGFR, KRAS, and CD74-ROS1 1 BRAF mutations were detected in 30 (56%), 25 (46%), and 0 samples, BRAF V600E 1 KRAS G12C 20 respectively. The median mutant allele frequency (MAF) for all – KRAS other 15 mutations detected by OncoBEAM was 0.50% (range: 0.04 50.84%), ERBB2 ins 20 3 where 64% and 23% of mutations were detected with MAF <1% and ERBB2 V659E 1 <0.1%, respectively. Concordance of results between OncoBEAM and MET ex 14 skipping 3 SafeSEQ in 176 replicate samples revealed an overall percent agreement of 99.6% with strong linear correlation of MAF (R2 = 0.98). Conclusions: OncoBEAM LB enables sensitive and accurate genotyping results within 5 days, ∼3x faster than the TAT of tissue genotyping Conclusions: G360 ctDNA NGS increased breadth and speed of results, which carries significant implications for enabling rapid actionable genomic variant detection. Upfront use of ctDNA NGS implementation of targeted therapies for NSCLC patients. should be considered routinely for NSCLC at diagnosis and relapse. Legal entity responsible for the study: The authors. Legal entity responsible for the study: The authors. Funding: Sysmex Inostics. Funding: Has not received any funding. Disclosure: H. Sloane: Full/Part-time employment: Sysmex Inostics, Inc. Disclosure: W. Cui: Research grant/Funding (self ): Breast Cancer Trials group; D. Edelstein: Full/Part-time employment: Sysmex Inostics, Inc. F. Jones: Full/ Research grant/Funding (self ): Australian Government Research Training Part-time employment: Sysmex Inostics, Inc. J. Preston: Full/Part-time employ- scholarship. C. Milner-Watts: Honoraria (self ): AstraZeneca. A.R. Minchom: ment: Sysmex Inostics, Inc. F. Holtrup: Full/Part-time employment: Sysmex Honoraria (self ), Advisory/Consultancy: Janssen Pharmaceutica; Honoraria Inostics, Inc. H. Quinn: Full/Part-time employment: Sysmex Inostics, Inc. All other (self ), Advisory/Consultancy: Merck Pharmaceuticals; Honoraria (self ): Novartis authors have declared no conflicts of interest. Oncology; Honoraria (self ): Bayer Pharmaceuticals; Honoraria (self ): Faron Pharmaceuticals; Travel/Accommodation/Expenses: LOXO oncology. S. Scott: Shareholder/Stockholder/Stock options, Full/Part-time employment: Guardant Health. I. Faull: Leadership role, Shareholder/Stockholder/Stock options, Full/ Part-time employment: Guardant Health. R.J. Nagy: Shareholder/Stockholder/ 165P Stock options, Full/Part-time employment: Guardant Health. M.E.R. O’Brien: Baseline circulating myeloid-derived suppressor cells Advisory/Consultancy: MSD; Advisory/Consultancy: AbbVie; Advisory/ correlate with neutrophil-to-lymphocyte ratio and overall Consultancy: Roche; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: BMS. S. Popat: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche; survival in advanced non-small cell lung cancer patients Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Pfizer; treated with immune checkpoint inhibitors Advisory/Consultancy: Novartis; Advisory/Consultancy: Takeda; Advisory/ Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: EMD J. Garcia-Sanchez1, M. Benet2, L. Cordon3, M. Piqueras2, Serono; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Bayer; 4 5 2 6 Advisory/Consultancy: Blueprint; Advisory/Consultancy: Daiichi Sankyo; J. Garde-Noguera , M. de Julian , L. Gonzalez-Castillo , D. Lorente , Advisory/Consultancy: Janssen; Advisory/Consultancy: GSK; Advisory/ N. Piera4, M.C. Gomez-Soler4, V. Ruiz2, J. Carretero7, Consultancy: BeiGene; Advisory/Consultancy: Incyte; Advisory/Consultancy: Eli A. Sanchez-Hernandez6, O. Juan-Vidal2, A. Lahoz2 1Medical Oncology Lilly; Advisory/Consultancy: Amgen. All other authors have declared no conflicts 2 of interest. Department, Hospital Arnau de Vilanova, Valencia, Spain; Biomarkers and Precision Medicine Unit, Instituto de Investigacioń Sanitaria La Fe, Valencia, Spain; 3Flow Cytometry Unit, Instituto de Investigacioń Sanitaria La Fe, Valencia, Spain; 4Medical Oncology Department, Hospital Arnau de 164P Vilanova, Valencia,̀ Spain; 5Medical Oncology Department, Hospital Rapid liquid biopsy genotyping in NSCLC patients Universitario Doctor Peset, Valencia, Spain; 6Medical Oncology Department, Hospital Provincial de Castellon,́ Castelloń De La Plana, 1 2 2 2 2 P. Sathyanarayan , H. Sloane , D. Edelstein , F. Jones , J. Preston , Spain; 7Physiology Department, Universidad de Valencia, Valencia, Spain S. Wu1, J. Los1, F. Holtrup2, H. Quinn2, D. Feller-Kopman1 1Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Sysmex Background: Immune Checkpoint Inhibitors (ICI) have become a care Inostics, Inc., Baltimore, MD, USA standard in advanced non-small cell lung cancer (aNSCLC). Myeloid- Derived Suppressor Cells (MDSC) are potent immunity suppressors and Background: Circulating tumor DNA (ctDNA) based liquid biopsies (LB) may represent both a potential prognostic and a predictive biomarker. have significantly advanced clinical care for NSCLC patients by Neutrophil-to-Lymphocyte Ratio (NLR) is an inflammatory biomarker improving access to molecular testing. A key benefit of certain LB with a prognostic role in NSCLC. We hypothesized that MDSC levels approaches is fast turnaround time (TAT), which can accelerate correlate with NLR and overall survival (OS) in aNSCLC. treatment initiation. We prospectively evaluated the feasibility, accuracy, Methods: Pretreatment immunophenotyping of total MDSC (HLA- and TAT of OncoBEAM EGFR, KRAS and BRAF genotyping in a cohort of DR−/CD33+/CD11b+), early-MDSC (e-MDSC: CD14−/CD15−), mono- NSCLC patients seen at a single institution in routine clinical practice. cytic-MDSC (M-MDSC: CD14+/CD15−) and polymorphonuclear-MDSC Alterations in these genes directly inform the use of approved (EGFR, (PMN-MDSC: CD14−/CD15+) was performed by flow cytometry in fresh BRAF) and emerging (KRAS G12C) targeted therapies, and due to mutual blood. Spearman’s rank correlation, univariate and multivariate Cox exclusivity with gene fusions in ALK/ROS/RET, may obviate the need for proportional hazard models were used for data analysis (SPSS Statistics additional molecular testing. v20). Methods: Whole blood samples (n = 187) were collected from Results: 100 patients treated with ICI who received at least one previous metastatic NSCLC patients and sent to a CLIA lab for OncoBEAM platinum-based combination chemotherapy for stage III–IV NSCLC and digital PCR analysis of EGFR (exon 19 del, L858R, T790M, C797S), KRAS 14 healthy donors were prospectively included; 93% smokers, median (codons 12, 13, 61), and BRAF V600E. Forty samples were analyzed age 63 years (range 38–80); 60% non-squamous and 50% PDL1 ≥1%. prospectively to assess TAT and 147 samples were analyzed retrospect- Median PFS (mPFS) and mOS was 2.98 m (95% CI, 0.92–4.85) and ively. Samples with sufficient residual plasma (n = 176) were tested with April 2021 Abstracts S789

11.83 m (95% CI, 9.46–13.85). Pretreatment high-NLR, dichotomized at negative patients, anlotinib combines with chemotherapy or sintilimab a ROC curve analyses cutoff value ≥5.17, and high level of total MDSC, also may be a promising first-line treatment. defined by the median value as a cut-off (≥6.3%), were correlated with Clinical trial identification: NCT03628521. poor PFS (NLR: p = 0.042 and MDSC: p = 0.038) and OS (NLR: p < Legal entity responsible for the study: Baohui Han. 0.0001 and MDSC: p = 0.004). Pretreatment low e-MDSC (<21.1%), were Funding: Shanghai Jiao Tong University. also associated with poor PFS (p = 0.02) and OS (p = 0.03). Both total Disclosure: All authors have declared no conflicts of interest. MDSC (Spearman’s rho = 0,40; p < 0.0001) and PMN-MDSC (Spearman’s rho = 0.29; p < 0.0001) were positively correlated with NLR. Multivariate analyses confirmed that higher NLR and higher total 167P MDSC levels were independently associated with shorter OS (NLR HR Chemotherapy-induced neutropenia and treatment efficacy 3.45; p = 0.005 and total MDSC HR 3.24; p = 0.021). in advanced non-small cell lung cancer (aNSCLC): A pooled Conclusions: Our study suggests that a baseline circulating MDSC analysis of 6 randomized trials correlate with NLR. Higher total MDSC levels and higher NLR were negative prognostic factors. The role of MDSC appears interesting as a P. Gargiulo1, R. Di Liello1, L. Arenare1, C. Gridelli2, A. Morabito3, potential predictive and prognostic biomarker in NSCLC patients treated F. Ciardiello4, V. Gebbia5, P. Maione2, A. Spagnuolo2, G. Palumbo3, with ICI. G. Esposito3, C.M. Della Corte4, F. Morgillo4, G. Mancuso5, A. Gravina1, Legal entity responsible for the study: Instituto de Investigacioń C. Schettino1, M. Di Maio6, C. Gallo7, F. Perrone1, M.C. Piccirillo1 Sanitaria - Fundacioń para la Investigacioń del Hospital Universitario la 1Clinical Trials Unit, Istituto Nazionale Tumori, IRCCS, Fondazione Fe. G. Pascale, Naples, Italy; 2Division of Medical Oncology, Azienda Funding: Roche Farma, S.A. Ospedaliera S. Giuseppe Moscati, Avellino, Italy; 3Thoracic Medical Disclosure: All authors have declared no conflicts of interest. Oncology, Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Naples, Italy; 4Medical Oncology, Precision Medicine Department, Universitàdegli Studi della Campania Luigi Vanvitelli, Naples, Italy; 5Medical Oncology, La 166P Maddalena Clinic for Cancer, Department Promise, Universitàdi Palermo, First-line anlotinib-based combination treatment for patients Palermo, Italy; 6Department of Oncology, University of Turin, Ordine with advanced non-small cell lung cancer: A threearm, Mauriziano Hospital, Turin, Italy; 7Medical Statistics, Universitàdegli Studi prospective study della Campania Luigi Vanvitelli, Naples, Italy Background: Chemotherapy-induced neutropenia (CIN) has a prognos- B. Han, T. Chu, W. Zhang, B. Han, X. Zhang, C. Shi, R. Zhong, H. Zhong, tic role in several cancer conditions. We previously demonstrated a W. Wang, A. Gu Respiratory Dept., Shanghai Chest Hospital Affiliated to significant prognostic value of CIN on overall survival (OS) in a pooled Shanghai Jiao Tong University, Shanghai, China dataset of pts with aNSCLC receiving first line chemotherapy (CT) from Background: Anlotinib, an oral multi-target TKI antiangiogenic 1996 to 2001. However, the prognostic role of CIN in NSCLC is still Inhibitor, has been recommended by guidelines for the 3rd line or debated. more treatment of NSCLC in China, but its effectiveness in combination Methods: We performed a post hoc analysis pooling data prospectively in first-line treatment remains unknown. Therefore, this study aimed to collected in six randomized phase III trials in aNSCLC conducted from evaluate efficacy and safety of anlotinib in combination with erlotinib, 2002 to 2016: CALC1 (NCT00330746), GECO (NCT00385606), TORCH chemotherapy or sintilimab, respectively. (NCT00349219), MILES2 (NCT00401492), MILES3 (NCT01405586) Methods: In this open-label, threearm, prospective study, advanced and MILES4 (NCT01656551). All trials tested first-line treatment and NSCLC patients with EGFR mutation (Cohort A) receive anlotinib and primary results have already been published. Pts assigned to CT arms or erlotinib; for patients with EGFR mutation negative, the treatment combination arms of CT with other non-cytotoxic drugs (rofecoxib in regimen was anlotinib in combination with chemotherapy (Cohort B) or GECO and cetuximab in CALC1), that had received at least one cycle of CT sintilimab (Cohort C) according to investigator. All patients received and for whom at least one toxicity case report form was available, were treatment until disease progression or treatment intolerance. The considered eligible for the analysis. Neutropenia was categorized on the primary outcome was ORR, the secondary outcomes were PFS, DCR, basis of worst NCI-CTC/CTCAE grade during CT: absent (G0), mild (G1– OS and safety. 2), or severe (G3–4). The primary endpoint was OS. Multivariable Cox Results: A total of 80 patients were enrolled, in Cohort A 30 patients, model was applied for statistical analyses. A landmark at 180 days from Cohort B 28 patients and Cohort C 22 patients. The final follow-up randomization was applied to minimize the time-dependent bias. deadline was 20 Dec 2020, In Cohort A, 26 patients achieved confirmed Results: Overall, 1529 out of 1963 pts enrolled in the trials were PR, ORR was 92.9%, and DCR was 96.4%. Median PFS was 20.5 months, considered eligible. 572 of them (who received 6 cycles of treatment) and 12-month PFS rate was 81.5%. In Cohort B, ORR was 60.0%, while represented the landmark population. Severe CIN was reported in 143 DCR was 96.7%. Median PFS was 13.3 months, and 12-month PFS rate (25.0%) pts and mild CIN in 135 (23.6%). At multivariable OS analysis, was 55.5%. In Cohort C, medium PFS was 15.6 months. The 18- and 24- CIN was significantly predictive of prognosis although its prognostic month PFS rate was 45.9% and 26.2%, respectively. The median OS of value was entirely driven by severe CIN (HR of death 0.71; 95%CI: 0.53– the three arms has not been reached. The most common grade 3 adverse 0.95) while it was not evident with mild CIN (HR 1.21; 95%CI: 0.92– events (AEs) were rash (17.2%), oral mucositis (10.3%), diarrhea 1.58). Consistent results were observed in the out-of-landmark group (6.9%) and proteinuria (6.9%) in Cohort A, and a grade 4 hypertension (including 957 pts), where both severe and mild CIN were significantly was observed. In Cohort B, the most common grade 3 AEs were platelet associated with a reduced risk of death. count decreased (20.0%), leucopenia (16.7%), hand-foot-skin reaction Conclusions: This pooled analysis of six large trials of aNSCLC (10.0%), hypertriglyceridemia (10.0%), oral mucositis (6.7%) and treatment shows a significant improvement of OS in pts developing thrombus (6.7%). Safety data of Cohort C has been published elsewhere. CIN, particularly in those developing severe CIN, confirming our Conclusions: This study suggests that anlotinib-based combination previous findings. therapy for patients with advanced NSCLC might be a new first-line Legal entity responsible for the study: The authors. therapy strategy. For EGFR-mutated positive patients, anlotinib plus Funding: Has not received any funding. erlotinib shows good efficacy and tolerability. For EGFR-mutated Disclosure: C. Gridelli: Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; S790 Journal of Thoracic Oncology Vol. 16 No. 4S

Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/ 5–14) & 16 (IQR = 9–23) respectively. 54/59 patients received ≥1 cycle Consultancy: Novartis; Advisory/Consultancy: Amgen; Advisory/Consultancy: & 27 underwent post-C4 evaluation with detectable cfDNA levels in 18/ Menarini. A. Morabito: Advisory/Consultancy: Pfizer; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Takeda; Advisory/ 27 (6.7%). No baseline characteristic correlated with cfDNA detect- Consultancy: AstraZeneca; Advisory/Consultancy: Boehringer; Advisory/ ability. Median OS & PFS were 262 days & 167 days respectively. ECOG Consultancy: Eli-Lilly; Advisory/Consultancy: Roche. F. Ciardiello: Advisory/ PS>2, RSB score >9 & TSB score >16 were all associated with worse OS & Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, PFS as was cfDNA detectability [Median OS = 97 vs. 271 days; p = 0.045; Research grant/Funding (institution): Merck; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Research grant/Funding HR = 2.32Median PFS = 93 vs. 182 days; p = 0.027; HR = 2.28]. (institution): Bayer; Advisory/Consultancy: Servier; Advisory/Consultancy: BMS; Conclusions: Baseline cfDNA detectability is independently associated Advisory/Consultancy: Celgene; Advisory/Consultancy: Lilly; Research grant/ with poor OS and PFS in advanced Sq-NSCLC patients on chemotherapy. Funding (institution): AstraZeneca; Research grant/Funding (institution): Ipsen; Legal entity responsible for the study: The authors. Advisory/Consultancy, Research grant/Funding (institution): Roche. V. Gebbia: Speaker Bureau/Expert testimony: Eli-Lilly. C.M. Della Corte: Advisory/ Funding: Has not received any funding. Consultancy: MSD. F. Morgillo: Research grant/Funding (institution): Disclosure: All authors have declared no conflicts of interest. AstraZeneca; Advisory/Consultancy: MSD; Advisory/Consultancy: Lilly. A. Gravina: Travel/Accommodation/Expenses: Pfizer. M. Di Maio: Research grant/Funding (institution): Tesaro-GlaxoSmithKline; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; 169P Advisory/Consultancy: Novartis; Advisory/Consultancy: Janssen; Advisory/ BEPACT lung: A prospective, multicenter, non-interventional Consultancy: Astellas; Advisory/Consultancy: Takeda; Advisory/Consultancy: Eisai; Advisory/Consultancy: Merck Sharp & Dohme. F. Perrone: Advisory/ study of decision factors in the first-line treatment of Consultancy: Bayer; Advisory/Consultancy: Ipsen; Advisory/Consultancy: metastatic non-small cell lung cancer (NSCLC) AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: Sandoz; Advisory/Consultancy: Incyte; Advisory/Consultancy: Celgene; Advisory/ A. Sibille1, F. Bustin2, C. Compere3, K. Cuppens4, S.H. Coulon5, Consultancy: Pierre Fabre; Advisory/Consultancy: Janssen-Cilag. M.C. Piccirillo: 6 7 8 9 Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: GSK; Advisory/ L. Decoster , L. Decoster , I. Demedts , K. Deschepper , 10 11 12 13 14 Consultancy: MSD; Research grant/Funding (institution): Roche; Advisory/ A. Janssens , S. Ocak ,C.Oyen , K.E. Pat , T. Pieters , Consultancy, Research grant/Funding (institution): AstraZeneca; Travel/ V. Pruniau15, J.F. Vansteenkiste16 1Pulmonology, Centre Hospitalier Accommodation/Expenses: Bayer. All other authors have declared no conflicts of Universitaire Sart Tilman, Liege,̀ Belgium; 2Centre Hospitalier Regionaĺ de interest. la Citadelle, Liege,̀ Belgium; 3Delta Hospital - Chirec, Brussels, Belgium; 4Pulmonology Department, Virga Jesse Ziekenhuis, Hasselt, Belgium; 5Oncology, MSD Belgium BVBA/SPRL, Woluwe-Saint-Lambert, Belgium; 168P 6Department of Medical Oncology, UZ Brussel - Universitair Ziekenhuis Changes in cfDNA levels in squamous non-small cell lung Brussel, Jette, Belgium; 7AZ Turnhout - Campus St. Elisabeth, Turnhout, cancer with chemotherapy: Correlation with symptom scores Belgium; 8AZ Delta campus Wilgenstraat, Roeselare, Belgium; and radiological responses 9Respiratory Diseases Department, AZ Nikolaas Hospital, St Niklaas, Belgium; 10Thoracic Oncology, University Hospital Antwerp (UZA), 1 1 2 3 4 1 N. Singh ,N.Ravi , A. Bal , M. Garg , R. Kapoor , K.T. Prasad Edegem, Belgium; 11Internal Medicine, CHU UCL Namur - Site Godinne, 1 Pulmonary Medicine, PGIMER - Postgraduate Institute of Medical Yvoir, Belgium; 12Pulmonology, University Hospitals KU Leuven, Leuven, 2 Education and Research, Chandigarh, Chandigarh, India; Histopathology, Belgium; 13Pulmonology, Jesse Ziekenhuis - Campus Virga Jesse, Hasselt, PGIMER - Postgraduate Institute of Medical Education and Research, Belgium; 14Pulmonology, Cliniques Universitaires Saint-Luc (UCLouvain 3 Chandigarh, India; Radiodiagnosis and Imaging, PGIMER - Postgraduate Saint-Luc), Woluwe-Saint-Lambert, Belgium; 15Oncology Medical Affairs Institute of Medical Education and Research, Chandigarh, India; Department, MSD Belgium BVBA/SPRL, Woluwe-Saint-Lambert, Belgium; 4 Radiotherapy, PGIMER - Postgraduate Institute of Medical Education and 16Respiratory Oncology Unit (Pulmonology), University Hospitals Leuven - Research, Chandigarh, India Campus Gasthuisberg, Leuven, Belgium Background: There is limited data on prognostic value of baseline Background: Rapidly evolving treatment options for advanced NSCLC plasma cfDNA in advanced squamous NSCLC. The current study aimed to can lead to difficulties in implementing those changes in daily practice. assess change in plasma cfDNA levels in locally advanced/metastatic Sq- Insight into real-world treatment choices might help identify needs for NSCLC with chemotherapy & its correlation with symptom scores & better patient care. radiological responses. Methods: 215 consecutive metastatic treatment-naïve NSCLC patients Methods: Prospective observational study involving chemotherapy- were prospectively enrolled in BEPACT Lung (NCT03959137) between th naïve stages IIIB/IIIC/IV (8 TNM) Sq-NSCLC patients at a tertiary June-Oct 2019 in 21 Belgian hospitals. Data collected: treatment site referral centre. Being a pilot study, enrolment was planned for 50 Sq- (high vs low volume (HV vs LV)); patients’ characteristics (demograph- NSCLC patients, 25 smokers with COPD (COPD-controls; CC) & 25 ics, medical history, comorbidities, autoimmune disease, medications, healthy controls (HC). Respiratory Symptom Burden (RSB) was prior treatment for earlier stage NSCLC); tumor characteristics; patients’ calculated from mean Visual Analog Scores (VAS) of dyspnoea, cough, preference; treatment type (chemotherapy (C), immunotherapy (I), chest pain & hemoptysis. Total Symptom Burden (TSB) was calculated immuno-chemotherapy (I+C), best supportive care (BSC)). The primary from mean VAS scores of above 4 symptoms + anorexia & fatigue. cfDNA objective was to identify factors influencing the treatment choice using was isolated >2 hours of obtaining 5 ml of peripheral blood using first a simple logistic regression model, and then entering factors with TM MagMAX Cell-Free DNA Isolation Kit. It was analyzed & quantitated p < 0.25 in a multiple logistic regression model. TM TM using Agilent High Sensitivity DNA Kit & Agilent Bioanalyzer 2100. Results: HV and LV centers showed similar patients’ characteristics. All patients received standard platinum-doublet chemotherapy. RSB/ Median age 68.2 years, 65.1% male, 77% performance status (PS) ≤1, TSB/cfDNA assessment & CECT scans of thorax were all done at baseline 95.7% (former)smokers, 65.6% non-squamous, 42.1% Programmed & after 4 chemotherapy cycles. Death-Ligand1 (PD-L1) high (≥50%). In the PD-L1 high group, simple Results: Final enrolment was 59 Sq-NSCLC, 27 CC & 25 HC. At baseline, logistic regression pointed at age (p = .0167), prior treatment (p = 13/59 (22%) Sq-NSCLC, 3/27 (11%) CC & none (0%) HC had detectable .0544), tumor size (p = .0643), number of comorbidities (p = 0.1679) cfDNA. All 3 CC were heavy smokers with no evidence of malignancy & and weight loss (p = .2146) as factors in the choice of I alone vs I+C; in undetectable cfDNA levels on repeat testing. In Sq-NSCLC group, the multiple regression model, this was age (p = .0642), weight loss (p = majority were males (95%), current smokers (88%), heavy smokers .0458) and prior treatment (p = .0582). In the PD-L1 low group, simple (70%), had metastatic disease (59%) with median age of 65 years. ECOG logistic regression pointed at PS (p < 0.0001), weight loss (p = .0440), PS was 0–1 (56%) and 2 (42%). Median RSB & TSB scores were 9 (IQR = patients’ preference (p = .0636), age (p = .1149), antibiotics (p = .1366) April 2021 Abstracts S791 and smoking status (p = 0.1566) for the choice of I+C vs C alone or BSC; Results: Eighty-four patients with LC with a mean age of 61.5 years were in multivariate analysis, this was PS (p = .0005), age (p = .0308), and included in the present study. The prevalence of CRF was 48.80%. patients’ preference (p = .0585). Univariate analysis revealed that the presence of cough (p < 0.001), Conclusions: In PD-L1 high tumors, the choice of I alone (vs I+C) was breathlessness (p < 0.001), hemoglobin levels (p = 0.012), and radio- more likely with higher age, more weight loss, and no prior treatment. In therapy treatment (p = 0.038) to be associated with fatigue. After PD-L1 low tumors, the choice of I+C (vs C alone/BSC) was more likely in multiple logistic regression analysis with fatigue as outcome variable, case of good PS, younger age or patients’ preference. revealed that presence of cough [OR = 3.80; 95% CI = 1.13 to 12.80;(p = Clinical trial identification: NCT03959137 Study Start date: June 1, 0.031)] and breathlessness [OR = 3.57; 95% CI = 1.19 to 10.73; (p = 2019 Study Completion date: October 31, 2019. 0.023)] as significant predictors affecting fatigue among lung cancer Legal entity responsible for the study: Merck Sharpe & Dohme Corp. patients. Funding: Merck Sharpe & Dohme. Conclusions: Half of our patients with LC had CRF. The presence of Disclosure: A. Sibille: Advisory/Consultancy: AstraZeneca; Advisory/ cough and breathlessness were significant factors that affected the CRF Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Bristol Myers in the present study after the confounding factors were adjusted. Further Squibb; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: studies on this associated symptom cluster of fatigue, breathlessness, Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/ Consultancy: Takeda. K. Cuppens: Advisory/Consultancy: Merck Sharpe & Dohme; and cough have to be conducted. While managing the patients with Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bristol Myers Squibb; fatigue it is important that these associated symptoms like cough and Advisory/Consultancy: Roche. S.H. Coulon: Full/Part-time employment: Merck breathlessness have to be handled. Sharpe & Dohme. L. Decoster: Honoraria (institution): Lilly; Advisory/ Legal entity responsible for the study: The authors. Consultancy: Roche; Research grant/Funding (self ): Boehringer Ingelheim; Travel/Accommodation/Expenses: Merck Sharp & Dohme; Travel/ Funding: Has not received any funding. Accommodation/Expenses: Roche. I. Demedts: Advisory/Consultancy: Merck Disclosure: All authors have declared no conflicts of interest. Sharpe & Dohme; Advisory/Consultancy: Boehringer Ingelheim; Advisory/ Consultancy: Bristol Myers Squibb; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/ Consultancy: Pfizer; Advisory/Consultancy: Takeda; Advisory/Consultancy: Lilly; 171P Advisory/Consultancy: Glaxo Smith Kline. K. Deschepper: Advisory/Consultancy: Association between patient-reported toxicity and health- Merck Sharpe & Dohme; Advisory/Consultancy: Bristol Myers Squibb; Advisory/ Consultancy: AstraZeneca; Advisory/Consultancy: Lilly; Research grant/Funding related quality of life in (locally-) advanced non-small cell (institution): Merck Sharpe & Dohme; Research grant/Funding (institution): lung cancer Chiesi. A. Janssens: Advisory/Consultancy: AstraZeneca. S. Ocak: Advisory/ Consultancy: Merck Sharpe & Dohme; Advisory/Consultancy: Boehringer L. Van Der Weijst1, V. Surmont2, W. Schrauwen3, Y. Lievens1 Ingelheim; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: 1 AstraZeneca; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Radiation Oncology, Ghent University Hospital, Gent, Belgium; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Takeda. V. Pruniau: Full/ 2Respiratory Medicine/Thoracic Oncology, Ghent University Hospital, Part-time employment: Merck Sharpe & Dohme. J.F. Vansteenkiste: Advisory/ Gent, Belgium; 3Medical Psychology, Ghent University Hospital, Gent, Consultancy: Merck Sharpe & Dohme; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Belgium Advisory/Consultancy: Novartis; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sanofi; Research grant/ Background: Because of the poor prognosis of lung cancer, it is Funding (institution): Merck Sharpe & Dohme. All other authors have declared no important to take into account the quantity and quality of survival in conflicts of interest. treatment decision-making. It is therefore important to consider the impact of toxicity on health-related quality of life (HRQoL). We report the results on the association between patient-reported HRQoL and toxicity 170P in stage locally advanced (LA-) and metastatic non-small cell lung cancer Predictors for cancer-related fatigue among patients with (NSCLC) patients receiving systemic therapy and/or radiotherapy in the PRO-Long study. advanced lung cancer attending palliative care department: A Methods: PRO-Long is a prospective, longitudinal study on the effect of prospective observational study systemic therapy and/or radiotherapy on HRQoL, toxicity, functional exercise capacity and neuro-cognitive functioning in LA- and metastatic C.R. Patil1, S. Atreya2 1Palliative Medicine and Psycho Oncology NSCLC patients. HRQoL and toxicity data was collected pre-therapy and Department, Kolhapur Cancer Centre, Kolhapur, India; 2Palliative repeatedly until 1 year after therapy, respectively with the European Medicine and Psycho Oncology Department, Tata Medical Center, Kolkata, Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 India and Patient-Reported Outcomes version of the Common Terminology Background: Cancer-related fatigue (CRF) among patients with lung Criteria for Adverse Events (PRO-CTCAE). HRQoL scores were calculated cancer (LC) is present before and after treatment and present in about based on EORTC guidelines. Overall toxicity scores were translated into three fourth of cases. CRF is often a common unmet need affecting the the Standardized Total Average Toxicity (STAT) score. Individual toxicity quality of life of patients with LC. We conducted this study to understand scores were calculated by subtracting baseline scores from subsequent the predictors for CRF among patients with LC attending the palliative data point scores. Multi-level analyses were applied to assess statistical care department in our center. significance (<0.01). Methods: A prospective observational study was conducted among Results: In total, 50 patients were recruited. The majority had stage III patients having LC. The study was conducted on patients referred to the disease (54%), was male (60%) and received chemotherapy with (50%) palliative care department of Tata Medical Center, Kolkata from January or without (24%) radiotherapy. Toxicity is associated with overall 2019 to June 2019. Those patients whose Karnofsky status is less than HRQoL (p = 0.000) and physical (p = 0.000), cognitive (p = 0.000), role 40, with a history of diabetes, heart disease, psychiatric disease, and (p = 0.000) and emotional (p = 0.000) functioning. HRQoL is associated psychotropic drugs were excluded from the study. Edmonton Symptom with loss of appetite (p = 0.000), fatigue (p = 0.000), dyspnea (p = Scale was used to assess the various symptoms like pain, fatigue, nausea, 0.001), cough (p = 0.000), diarrhea (p = 0.000), constipation (p = depression, anxiety, appetite, well-being, cough, and shortness of breath. 0.008), anxiety (p = 0.007) and depression (p = 0.000). Fatigue, cough History of any surgery, chemotherapy, or radiotherapy along with blood and depression significantly impact the majority of HRQoL domains. investigations like serum albumin, hemoglobin, and white blood cell Conclusions: Toxicity may impact overall and certain HRQoL domains in count was documented. LA- and metastatic NSCLC patients receiving systemic or combined therapy. It is therefore important to consider the impact of toxicity on HRQoL in this vulnerable patient population. S792 Journal of Thoracic Oncology Vol. 16 No. 4S

Legal entity responsible for the study: The authors. Funding: Funding Agency for Innovation by Science and Technology 173P (IWT), Brussels, Belgium. Contract number: IWT TBM 130262. Evaluating the content validity, clarity, and relevance of the Disclosure: All authors have declared no conflicts of interest. PROMIS-physical function (PROMIS-PF)-8C and non-small cell lung cancer (NSCLC)-Symptom assessment questionnaire (NSCLC-SAQ) in adults with epidermal growth factor receptor 172P (EGFR)-mutated NSCLC Anlotinib as treatment for advanced non-small cell lung cancer: A systematic review and meta-analysis on overall M.K. Horn1, K. Liu2, S.D. Mathias3, H.H. Colwell3,T.Li2, survival and progression free survival P. Mahadevia2, R.F. Pierson2 1ICAN, International Cancer Advocacy Network, Phoenix, AZ, USA; 2Janssen Pharmaceuticals, Raritan, NJ, USA; 1 1 1 1 1 B. Susanto , E. Marcella , S. Chen , R.S. Heriyanto , J. Tandiono , 3Health Outcomes Solutions, Winter Park, FL, USA F. Wijovi1, A. Tancherla1, A. Kurniawan2 1Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia; 2Department of Internal Background: Qualitative research was conducted with adults with Medicine, Pelita Harapan University, Tangerang, Indonesia EGFR-mutated NSCLC to debrief two patient-reported outcomes (PROs), the PROMIS-PF-8c and NSCLC-SAQ, confirm their content validity, and Background: Non-small cell lung cancer (NSCLC) is the most frequent ensure they are clear, relevant, and appropriate for use with this type of lung cancer that is associated with highest morbidity and population. mortality rate. Anlotinib is an inhibitor of epidermal growth factor Methods: Concept elicitation (CE) and combined CE/cognitive debrief- receptor (EGFR) tyrosine kinase that is used as third-line treatment for ing (CD) interviews were conducted with adults with locally advanced or NSCLC. The objective of this study was to evaluate the overall survival in metastatic EGFR-mutated NSCLC identified from lung cancer patient patients with advanced NSCLC treated with anlotinib. advocacy groups and online sources. The CE portion of the interview th Methods: Data was collected until January 5 2021 from PMC, PubMed, sought to understand important concepts of NSCLC. Subjects then Google Scholar, Science Direct, and Scopus, using combination of completed the PROMIS-PF-8c and NSCLC-SAQ, and answered questions keywords associated with advanced NSCLC and treatment using to evaluate their content, clarity, and relevance. The study received IRB anlotinib in relation to their overall survival. Publications included are approval; subjects provided written informed consent. limited to English manuscripts that were published in the past 10 years. Results: 30 patients were interviewed [87% female, 80% Caucasian, The studies include patients with advanced NSCLC and exclude patients mean age 57 ± 12 years, 63% from US, 70% with Exon20 insertion with brain metastases that were controlled or uncontrolled for less than mutation]. The most common NSCLC symptoms and impacts are two months. All studies were reviewed and evaluated by authors. The reported below. quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS), with four studies were in moderate quality and one study was in good quality. Studies were also assessed using GRADE and showed Table 173P moderate quality of evidence as there are neither inconsistency nor Symptoms % Endorsed publication bias. Fatigue 93% Results: A total of five studies consisting of four clinical trial studies and Shortness of breath 82% one cohort study with a total of 1,353 advanced NSCLC patients were Cough 71% included. Studies claimed that anlotinib showed better PFS (HR = 0.48; Weight loss 68% 95% CI: 0,23–1.00; P = 0.05) and significantly improved OS (HR = 0.75; Impacts 95% CI: 0.67–0.83; P < 0.00001) compared to the placebo group. One Emotional functioning 93% study also presented better PFS and OS in refractory advanced NSCLC Physical functioning 70% patients treated with anlotinib compared to the placebo group. Ability to perform daily activities 40% Conclusions: Anlotinib is proven to be beneficial compared to placebo in Social functioning 33% treating advanced NSCLC patients as it shows significant improvement in overall survival and also better progression free survival. Studies also The most bothersome symptoms were shortness of breath (43%), pain found that anlotinib possess remarkable efficacy and manageable safety other than chest pain (29%), cough (29%), and fatigue (21%). Fatigue profile, therefore should always be considered as candidate for was the most difficult symptom to manage (38%). In general, patients treatment in advanced NSCLC. were able to accurately paraphrase each item and found them to be clear, Legal entity responsible for the study: The authors. relevant, and meaningful. All symptoms and impacts were mapped to the Funding: Has not received any funding. content of these two PROs and were endorsed by > 20% of patients. One Disclosure: All authors have declared no conflicts of interest. of the most common impacts, difficulty with physical functioning, was covered in the PROMIS-PF-8c, while the NSCLC-SAQ contains all the most frequently reported NSCLC symptoms. Conclusions: Content validity of the PROMIS-PF-8c and NSCLC-SAQ has been confirmed in patients with EGFR-mutated NSCLC. Measurement properties will be evaluated using data from upcoming clinical studies. Legal entity responsible for the study: Janssen Global Services, LLC. Funding: Janssen Global Services, LLC. Disclosure: K. Liu: Full/Part-time employment: Janssen Pharmaceuticals. S.D. Mathias: Full/Part-time employment: Health Outcomes Solutions. H.H. Colwell: Full/Part-time employment: Health Outcomes Solutions. T. Li: Full/Part-time employment: Janssen Pharmaceuticals. P. Mahadevia: Full/Part-time employment: Janssen Pharmaceuticals. R.F. Pierson: Full/Part-time employment: Janssen Pharmaceuticals. All other authors have declared no conflicts of interest. April 2021 Abstracts S793

studied. This study has been planned to evaluate the incidence of brain 174P metastasis in NSCLC patients treated in our center. Safety and efficacy of anlotinib plus docetaxel in advanced Methods: It is a prospective observational study conducted in medical non-small cell lung cancer patients after failure of first-line oncology at our tertiary care center from Sep 2019- Sep 2020. A total of chemotherapy: Recent results from the ongoing phase II study 150 patients with lung cancer were registered in the department. Among them, 112 patients had advanced non-small cell carcinoma of the lung (ALTER-L024) (NSCLC), and they were enrolled in the study. MRI brain was taken at the time of diagnosis. B. Jin1, G. Wang2, Y.L. Zhang1,R.Wu3, J. Chen4, Y. Dong5, L.Y. Peng1 Results: The mean age at presentation was 60 years. The Median follow- 1Oncology Department, The First Affiliated Hospital of China Medical up was 15 months. Median overall survival in the study was 11 months. University, Shenyang, China; 2The Affiliated Zhongshan Hospital of Dalian Patients with brain metastasis had a median survival of 7 months, University, Dalian, China; 3Shengjing Hospital of China Medical University, whereas patients without brain metastasis had 13 months. Clinical Shenyang, China; 4The Second Affiliated Hospital of Dalian Medical profile, performance status, demographic characteristics, and imaging University, Dalian, China; 5Anshan Tumor Hospital, Anshan, China findings were noted at the presentation time and the results were Background: Docetaxel is the standard second-line chemotherapy drug analyzed as follows. for advanced NSCLC, but the treatment effect is still limited. Antiangiogenic drugs can also potentially support vessel normalization to help deliver chemotherapy drugs for better clinical benefit, in addition Table 175P to having anti-angiogenic and anti-tumor effects. Anlotinib, as one of the new antiangiogenic drugs, significantly improved both PFS and OS of No advanced NSCLC patients and were approved by NMPA as third-line Baseline characteristics of Patients (%) treatment in a phase III trial (ALTER0303). So here, we present recent Mean age 60 years data from a cohort of patients who received anlotinib plus docetaxel after <60 44 (39%) first-line chemotherapy in the prospective phase II clinical trial ALTER- >60 68 (61%) L024 (NCT03732001). Sex Methods: Advanced NSCLC patients progressed after first-line chemo- Male 69 (62%) Female 43 (38%) therapy were assigned to treat with docetaxel at a dose of 60 mg per Adenocarcinoma 86 (77%) square meter of body-surface area and anlotinib at a dose of 12 mg oral Squamous cell carcinoma 26 (23%) per day for 2 weeks every 3 weeks in the treatment group. Progression Brain metastasis 39 (35%) free survival (PFS) was primary endpoint, and objective response rate Male 19 (49%) (ORR), disease control rate (DCR) and safety were secondary endpoints. Female 20 (51%) Results: At data cut-off (November 4, 2020), we recruited 22 patients Adenocarcinoma 32 (82%) (pts) in the combination cohort of this phase II trial. Most pts were male Squamous cell carcinoma 7 (18%) (81.8%), former/current smokers (81.8%) and non-squamous cell Asymptomatic 12 (30%) Symptomatic 27 (70%) histology (68.2%). Among 17 pts who had received at least one tumor Synchronous metastasis 21 (19%) assessment, four pts achieved PR, twelve pts achieved SD and only one Contralateral lung metastasis 12 (57%) patient developed to disease progression. The ORR was 23.5% (4/17) Bone metastasis 5 (23%) while the DCR was 94.1% (16/17). The estimated median PFS was 5.9 months (not mature). The most common Grade 3 adverse events (AEs) were hand-foot syndrome (13.6%), myelosuppression (4.5%) and Conclusions: The study period is short, so that data on molecular constipation (4.5%), and no Grade4/5 observation. There were no abnormalities in patients with brain metastasis was not included in the unexpected treatment-related AEs (TRAES). data. Our study found that female patients were at higher risk for brain Conclusions: This recent analysis of the ALTER-L024 study demon- metastasis. Other risk factors were adenocarcinoma histology and age strates the encouraging clinical benefit and manageable safety profile of less than 60 years. There are no biomarkers to predict brain metastasis anlotinib plus docetaxel in patients who progressed on previous in NSCLC due to its molecular heterogeneity. The study will serve as a chemotherapy. baseline platform of clinical predictors of brain metastasis in NSCLC. Our Clinical trial identification: NCT03732001. future direction and research will be clinical predictors along with Legal entity responsible for the study: The authors. molecular driver mutations in NSCLC in detecting brain metastasis. Funding: Has not received any funding. Legal entity responsible for the study: Rajiv Gandhi Government Disclosure: All authors have declared no conflicts of interest. General Hospital, Madras Medical College. Funding: Has not received any funding. Disclosure: The author has declared no conflicts of interest. 175P Incidence and treatment outcomes of brain metastasis in advanced non-small cell lung cancer at presentation: An 176P experience from south India Neutrophil-to-lymphocyte ratio (NLR) and platelet-to- lymphocyte ratio (PLR) as prognostic markers in patients with K. Kaliyamurthi Medical Oncology Department, Madras Medical College, non-small cell lung cancer (NSCLC) Chennai, India M. Vitorino, T. Tomás, S. Almeida, M. Silva Hospital Professor Doutor Background: Brain metastasis is one of the significant problems in Fernando Fonseca EPE (Hospital Amadora/Sintra), Lisbon, Portugal patients with lung cancer. Most of the patients are asymptomatic at presentation. Prognosis and survival in these patients are lacking. Many Background: Immunotherapy has changed treatment of lung cancer studies that looked upon the incidence of brain metastasis at the over the last few years. Besides best outcomes with immune checkpoint presentation of NSCLC are retrospective. In India, brain metastasis inhibitors (ICI) compared with standard treatment, there are no frequency in patients with NSCLC at the presentation has not been well validated biomarkers. High NLR and PLR are markers of inflammation and have been associated with worse prognosis in patients treated with S794 Journal of Thoracic Oncology Vol. 16 No. 4S

ICI. In this study, we evaluate the prognosis of patients with NSCLC, Results: A total of 53 NSCLC patients met the criteria. Forty-six patients according to NLR and PLR, treated with ICI. had adenocarcinoma (88.7%) and no patients had squamous cell Methods: Retrospective analysis of 92 patients with NSCLC treated with carcinoma. Thirty-one patients (58.5%) received the standard S-1 ICI since January 2016 until June 2020. Pre-treatment NLR and PLR were regimen and 18 patients (34.0%) received the modified S-1 regimen. calculated by division of neutrophils and platelets by lymphocytes ORR was 1.9% (95% confidential interval (CI): 0.00–10.1%). Median measured in peripheral blood. NLR ≥ 5 and PLR ≥ 150 were considered TTF, PFS, and OS were 65 days, 84 days, and 385 days, respectively. high, according to literature data. Overall survival (OS) and progression Conclusions: Though there were several limitations in this study, the free-survival (PFS) curves were estimated using the Kaplan–Meier ORR of S-1 after PEM in patients with non-SQ NSCLC was low compared method. to the historical control. It might be one of the choices to avoid S-1 Results: From 92 patients with NSCLC treated with ICI, 65 (70.7%) were treatment in PEM-treated patients who need tumor shrinkage. male, with a median age of 62 years (range 38–83). Seventy-eight Legal entity responsible for the study: The authors. (84.8%) had stage IV disease and 14 (15.2%) received ICI in first-line Funding: Has not received any funding. treatment. Pembrolizumab was used in 35 (38%) patients, nivolumab in Disclosure: All authors have declared no conflicts of interest. 53 (57.6%) and durvalumab in 4 (4.3%). Median OS was 16.8 m (95% CI 7.98–25.60) in NLR <5 group and 5.5 m (95% CI 1.85–9.12) in NLR ≥5 – group (p = 0.003). Median PFS was 9.9 m (95% CI 4.57 15.28) in NLR <5 178P – ≥ group and 2.4 m (95% CI 0.99 3.87) in NLR 5 group (p = 0.008). Cox Neutrophil lymphocyte ratio (NLR) kinetics as a biomarker of regression analysis showed a better OS and PFS in NLR <5 group (HR = treatment response and outcome 2.43, 95% CI 1.33–4.44 and HR = 2.15, 95% CI 1.21–3.81, respectively). Median OS was 24.5 m (95% CI 6.03–43.05) in PLR <150 group and S. Subramaniam, S.S. Malwinder Clinical Oncology Department, UMMC 9.4 m (95% CI 4.37–14–50) in PLR ≥150 group (p = 0.041). - University Malaya Medical Centre, Kuala Lumpur, Malaysia Conclusions: Elevated pre-treatment NLR and PLR were associated with worse outcomes. Our results are in agreement with previous studies Background: Neutrophil Lymphocyte Ratio (NLR) at baseline has been showing that inflammation markers are potential predictors of response shown to be a biomarker of prognosis in many malignancies. However, in ICI treated patients. Prospective studies are required to validate these few studies have addressed if NLR kinetics (pre- and post-treatment) findings. affects treatment responses and outcomes. It has been postulated that Legal entity responsible for the study: The authors. NLR differences of more than double (over baseline) is associated with Funding: Has not received any funding. poorer outcomes. Disclosure: All authors have declared no conflicts of interest. Methods: This is a retrospective analysis. Records of all patients with Locally Advanced Lung Cancer (Stage 2B-3C) who were treated radically in Hospital Kuala Lumpur from 2012 to 2019 were analysed. There were 177P 18 patients with complete records (including available Full Blood Counts Efficacy of S-1 after pemetrexed in patients with non-small pre-treatment). Difference in NLR (baseline and post treatment) was cell lung cancer: A retrospective multi-institutional analysis calculated. The difference in NLR, as a ratio to the baseline NLR was calculated and tabulated as High (doubled or more) or low/stable (less S. Takemoto1, T. Suyama2, N. Honda2, Y. Umeyama2, Y. Dostu2, than double). G. Hiroshi2, H. Yamaguchi3, M. Fukuda4, H. Mukae1 1Respiratory Results: The median progression free survival (PFS) of patients with Medicine, Nagasaki University Hospital, Nagasaki Japan; 2Nagasaki high NLR was significantly shorter than those with low/stable NLR (12 University Hospital, Nagasaki, Japan; 3Respiratory Dept., Nagaski months vs 24 months, p = 0.02). The median overall survival showed a University Hospital, Nagasaki, Japan; 4Clinical Oncology Center, Nagaski trend towards improvement with low/stable NLR compared to high NLR University Hospital, Nagasaki, Japan (25months vs 14months, p = 0.063). Conclusions: An NLR value that doubles or more post treatment is Background: S-1 and pemetrexed (PEM) are key treatments for non- associated with worse outcomes. NLR is an acute phase reactant which is small cell lung cancer (NSCLC). PEM and cisplatin (CDDP), showed a systemic inflammatory marker. It has been hypothesized that superior overall survival (OS) compared with gemcitabine and CDDP in persistent inflammation is detrimental. NLR kinetics may be an index treating non-squamous (non-Sq) NSCLC patients, and PEM and platinum of response to treatment and prognosis that will need to assess in treatment is usually used for this population (1). S-1 monotherapy prospective studies. In conclusion, NLR which doubles or more post showed non-inferior OS compared with docetaxel in treated NSCLC treatment was associated with significantly worse progression free patients, and is also used for NSCLC as a standard therapy after first line survival and a trend towards worse overall survival. treatment (2). However, the mechanism of anticancer activity of S-1 and Legal entity responsible for the study: The authors. PEM is similar. For example, both S-1 and PEM target thymidylate Funding: Has not received any funding. synthase (TS) (3). Moreover, cross-resistance between S-1 and PEM is of Disclosure: All authors have declared no conflicts of interest. concern. Some preclinical studies indicated that elevation of TS expression after PEM treatment may be one of the causes of cross- resistance between S-1 and PEM (4,5). In addition, TS expression level is 179P associated with response to S-1 in NSCLC in a clinical setting (6). Resistance to PEM may indicate resistance to S-1. Unfortunately, studies Efficacy and safety of extended-interval dosing strategy of about the treatment effect of S-1 after PEM in the clinical setting are immune checkpoint inhibitors during the COVID-19 outbreak: limited. Experience from a single center Methods: This retrospective study included patients with advanced (c- 1 1 1 2 1 1 stage III or IV, UICC 7th) or recurrent NSCLC who received S-1 C. Pierre , T. Goter , C. Agar , S. Luzi , H. Lena , Y. Le Guen , 1 1 monotherapy following the failure of previous PEM-containing chemo- C. Ricordel Service de Pneumologie, CHU Rennes, Rennes, France; 2 therapy at 6 hospitals in Japan. Primary endpoint: Overall response rate Service de Radiologie, CHU Rennes, Rennes, France (ORR). Secondary endpoint: Disease control rate (DCR), time to Background: Question emerged during COVID-19 pandemic to minim- treatment failure (TTF), progression-free survival (PFS), and overall ize the risk of nosocomial viral exposure. Pharmacokinetic modelling survival (OS). evidence supports extended-interval dosing of ICI in advanced NSCLC, April 2021 Abstracts S795 showing equivalent pharmacological performance than standard radiotherapy, 8 were unfit for treatment, 2 died. 11/37 (30%) pts with schedule. However, there is a clear lack of clinical data. BM did not receive systemic therapy. Methods: We performed an observational, retrospective study in a French university hospital. The extended-schedule of ICI administration Table 180P: Characteristics began during the first pandemic period (from march to may 2020). We Brain report here the clinical characteristics and early efficacy and safety imaging N No brain imaging signals, after a minimal follow-up of 6 months. Data (tumor response, = 95 N (%) N = 77 N (%) adverse event) were collected based on medical records. Age Results: 25 patients received the extending-dose schedule (13 Median (range) 70 (34–95) 74 (47–91) pembrolizumab 400 mg Q6W, 12 nivolumab 480 mg Q4W) during the Smoking inclusion period. Most of the malignancies were stage IV (21/25) Never 20 (21%) 12 (16%) adenocarcinoma (20/25) with 13/25 tumors showing a PD-L1 Ex/current 74 (78%) 51 (66%) TPS>50%. Most of the patients were in 2nd or 3rd line of treatment NA 1 (1%) 14 (18%) (15/25). 3 patients started ICI with double dose-schedule, whereas 22 ECOG transitioned from a previous standard-dose regimen. Altogether, 13/25 0 16 (17%) 5 (6%) (52%) patients presented or remained on partial response with 1–2 68 (72%) 37 (48%) – extended-interval dosing schedule during follow-up, with 11/25 3 4 11 (11%) 27 (35%) NA 0 (0%) 8 (10%) (44%) continuing this regimen on september 1st. The adverse events Subtype reported in the patient still on ICI were grade 1 diarrhea or arthralgia. Adenocarcinoma 68 (72%) 45 (58%) The median duration of prior exposure to ICI for those patients was 278 Squamous cell 11 (12%) 12 (16%) days. 14 patients stopped the extended-interval dosing schedule Other 11 (11%) 4 (5%) including 7 for disease progression and 6 for immune-related adverse NA 5 (5%) 16 (21%) event. The main observed adverse events were asthenia (n = 4), diarrhea Molecular (n = 1) and arthralgia. The median duration of prior exposure to ICI for Variant detected 52 (55%) 25 (32%) those patients was 178 days. 3 patients died during the follow-up period. No variant 28 (29%) 31 (40%) No SARS-CoV2 infection was observed. NA 15 (16%) 21 (27%) BM symptoms Conclusions: This work based on real-life experience shows that Yes 32 (34%) 4 (5%)* extending the dose and interval of ICI treatment in advanced NSCLC is No 63 (66%) 60 (78%) feasible. Early efficacy and safety signals appear encouraging. The NA 0 13 (17%) adverse events reported were expected side-effects of immunotherapy Systemic therapy and no grade 4–5 toxicity was observed. NA 0 (0%) 2 (3%) Legal entity responsible for the study: CHU Rennes. Yes 64 (67%) 32 (42%) Funding: Has not received any funding. No 31 (33%) 43 (56%) Disclosure: All authors have declared no conflicts of interest. Poor ECOG Pt wishes Died Surgery/ 174532 2821201 radiotherapy only Monitor *Not for active treatment. 180P Incidence of brain metastases (BM) in newly diagnosed stage Conclusions: The incidence of de novo BM was high in pts with stage 4 IV NSCLC during COVID-19 NSCLC during COVID19 (39%), higher than historical rates (25%). Many pts with BM were asymptomatic (35%). Brain imaging should be 1 1 1 1 1 W. Cui , C. Milner-Watts , S. Saith , J. Bhosle , A.R. Minchom , considered in all pts with a new diagnosis of stage 4 NSCLC. Whether 1 1 1 2 3 M. Davidson , S. Page , I. Locke , N. Yousaf , S. Popat , early diagnosis and treatment of BM affects survival will need to be ’ 4 1 M.E.R. O Brien Department of Medicine (Lung), The Royal Marsden explored. 2 Hospital - NHS Foundation Trust, London, UK; Lung Unit, The Royal Legal entity responsible for the study: The authors. 3 Marsden Hospital - NHS Foundation Trust, London, UK; The Royal Funding: Has not received any funding. Marsden Hospital - NHS Foundation Trust, Imperial College London, Disclosure: W. Cui: Research grant/Funding (self ): Breast Cancer Trials group; 4 Institute of Cancer Research, London, UK; The Royal Marsden Hospital - Research grant/Funding (self ): Australian Government Research Training NHS Foundation Trust, Imperial College London, London, UK scholarship. C. Milner-Watts: Honoraria (self ): AstraZeneca. A.R. Minchom: Honoraria (self ), Advisory/Consultancy: Janssen Pharmaceutica; Honoraria Background: Reduced diagnostic procedures and late presentation (self ), Advisory/Consultancy: Merck Pharmaceuticals; Honoraria (self ): Novartis during COVID19 may lead to late diagnosis of NSCLC. De novo BM may Oncology; Honoraria (self ): Bayer Pharmaceuticals; Honoraria (self ): Faron Pharmaceuticals; Travel/Accommodation/Expenses: LOXO oncology. S. Popat: thus be more common during COVID19. Baseline incidence of BM in Honoraria (self ), Advisory/Consultancy: AstraZeneca; Honoraria (self ), Advisory/ asymptomatic patients (pts) needs to be defined. Consultancy: Roche; Honoraria (self ), Advisory/Consultancy: Boehringer Methods: Consecutive pts with stage IV NSCLC referred to Royal Ingelheim; Honoraria (self ), Advisory/Consultancy: Pfizer; Honoraria (self ), Marsden Hospital between Jun-Nov 2020 were included. Prospectively Advisory/Consultancy: Novartis; Honoraria (self ), Advisory/Consultancy: Takeda; Honoraria (self ), Advisory/Consultancy: BMS; Honoraria (self ), collected data were analysed descriptively. Advisory/Consultancy: MSD; Honoraria (self ), Advisory/Consultancy: EMD Results: Of 172 pts, 95 (55%) underwent brain imaging, 77 (45%) did Serono; Honoraria (self ), Advisory/Consultancy: Guardant Health; Honoraria not. More pts with brain imaging had good ECOG and received systemic (self ), Advisory/Consultancy: Bayer; Honoraria (self ), Advisory/Consultancy: therapy compared to those without brain imaging (table). 37/95 (39%) Blueprint; Honoraria (self ), Advisory/Consultancy: Daiichi Sankyo; Honoraria (self ), Advisory/Consultancy: Janssen; Honoraria (self ), Advisory/Consultancy: pts had BM on imaging. In pts with BM, 65% had BM symptoms, 35% did GSK; Honoraria (self ), Advisory/Consultancy: BeiGene; Honoraria (self ), not. 12/27 (44%) pts with 1–5 BM were asymptomatic compared to 1/ Advisory/Consultancy: Incyte; Honoraria (self ), Advisory/Consultancy: Eli Lilly; 10 (10%) pts with ≥6 BM (p = 0.07). 32/95 (34%) pts with brain Honoraria (self ), Advisory/Consultancy: Amgen. M.E.R. O’Brien: Advisory/ imaging had BM symptoms; of which 24 (66%) had BM confirmed on Consultancy: MSD; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Roche; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: BMS. All imaging. However, 13/63 (21%) asymptomatic pts also had BM detected other authors have declared no conflicts of interest. on imaging. 10/37 (27%) pts with BM received stereotactic radio- surgery, of which 5 were asymptomatic. Of the remaining 27 pts with BM, 12 received TKI alone, 1 was monitored, 4 received palliative S796 Journal of Thoracic Oncology Vol. 16 No. 4S

181P 182P Multicenter real-world study (RWS) on efficacy and early Impact of SARS CoV 2 outbreak in the molecular diagnosis of discontinuation predictors in non-small cell lung cancer advanced NSCLC: A retrospective comparative cohort study (NSCLC) patients (pts) receiving nivolumab E. Marin1, C. Teixido2, A. Arcocha3, S. Castillo4, R. Reyes3, G. Pasello1, A. Bortolami2, S. Tognazzo2, G. Crivellaro2, A. Torchia1, N. Viñolas1, L. Mezquita1, S. Muñoz4, D. Martinez5, P. Jares6, M. Lorenzi3, J. Menis1, S. Frega4, L. Bonanno5, V. Guarneri6, N. Reguart1 1Division of Medical Oncology, Translational Genomics and P.F. Conte1 1Department of Surgery, Oncology and Gastroenterology, Targeted Therapeutics in Solid Tumors, Unitat Funcional de Tumors University of Padova, Padua, Italy; 2Veneto Oncology Network, Istituto Toracics,̀ Hospital Clinic of Barcelona, Barcelona, Spain; 2Division of Oncologico Veneto IRCCS, Padua, Italy; 3Dipartimento di Oncologia Pathology, Translational Genomics and Targeted Therapeutics in Solid Medica, IOV - Istituto Oncologico Veneto IRCCS, Padua, Italy; Tumors, Unitat Funcional de Tumors Toracics,̀ Hospital Clinic of 4Dipartimento di Oncologia Medica 2, IOV - Istituto Oncologico Veneto Barcelona, Barcelona, Spain; 3Division of Medical Oncology, Unitat IRCCS, Padua, Italy; 5IOV - Istituto Oncologico Veneto IRCCS, Padua, Italy; Funcional de Tumors Toracics,̀ Hospital Clinic of Barcelona, Barcelona, 6Department of Surgery, Oncology and Gastroenterology, Istituto Spain; 4Division of Medical Oncology, Hospital General of Granollers, Oncologico Veneto IRCCS, Padua, Italy Granollers, Spain; 5Division of Pathology, Unitat Funcional de Tumors Toracics,̀ Hospital Clinic of Barcelona, Barcelona, Spain; 6Division of Background: RWS on immune checkpoint inhibitors treatment (tmnt) Pathology, Unitat Funcional de Tumors Toracics,̀ Molecular Biology Core outcome by matching data from administrative health flows (AHFs) and Facility, Hospital Clinic of Barcelona, Barcelona, Spain clinical records (CRs) may close the gap between randomized clinical trials and real practice. Background: The SARS CoV 2 coronavirus pandemic has rocked health Methods: We primarily investigated median time to tmnt failure (TTF) care systems to the core. Concurrent circulation of COVID 19 has led to and overall survival (OS) of NSCLC pts treated with nivolumab (N); mOS service disruptions and delays in the standard procedures related to lung in pts with and without early tmnt discontinuation (etd< 6 cycles). cancer (LC) diagnose and may negatively impact in the management, care Secondarily we investigated: clinical-pathological features predicting and therapeutic patient intervention. We aimed to determine COVID 19 etd; mOS and mTTF in patients treated with N vs. docetaxel (D). Pts were impact in the molecular diagnosis of LC at our institution. anonymously identified from the regional AHFs. Tmnt outcome were Methods: A total of 203 patients (pts) diagnosed with advanced NSCLC confirmed by CRs, as well as predictors of etd. with molecular testing requested in the period of 2019–2020 were Results: Overall, 237 NSCLC pts treated with N in 21 centres during included. Clinical characteristics and testing patient results evaluated in 2017 were identified from AHF; 141 patients received at least 6 tmnt 2019 and 2020 were compared. The SOC at our institution includes cycles, 96 received less than 6 cycles. mTTF and mOS in the overall evaluation of DNA and RNA from tissue(t) and/or blood(b) with NGS or population were 3.8 and 9.8 months, respectively. mOS in patients with nCounter. Single-gene testing by PCR, IHC and/or FISH is used as and without etd were 3.3 and 18.3 months (p < 0.0001), respectively. complementary assays to NGS when tissue is limited or in case of CRs of a subgroup of pts treated with N (n = 52) in 2017 or D (n = 29) in genomic platform service interruptions. 2014 from a single centre were analyzed for mTTF and mOS. mTTF was Results: A total of 106 and 97 pts were required for molecular testing 2.3 and 5.6 months respectively in patients treated with D and N (HR during 2019 and 2020 respectively. Clinical patient characteristics in 0.33; p < 0.0001); mOS was 6.1 and 12.6 months respectively in patients both cohorts were very similar and there were no significant differences treated with D and N (HR 0.48; p = 0.0024). These results were in the number of DNA-based or RNA-based analyses required between confirmed by the multivariate analysis. mOS was 2.9 and 16.5 months in both period times (DNAt p = 0.25; DNAb p = 0.59; RNAt p = .08). The patients with and without etd, respectively (HR 0.23; p < 0.0001). Of 2019 cohort identified 66 pts (65%) with driver genes: being KRAS the note, mOS did not differ between patients treated with D and those most commonly detected (34%), followed by EGFR 15%, BRAF 4%, ALK treated with N when etd occurred (mOS N: 2.9 vs. D: 6.1 months; HR 4% and METΔ14 4%. During 2020, driver alterations were found in 56 0.61; p = 0.15). Main reason for etd was clinical-radiological progression pts (60%) in a quite similar proportion except for KRAS mutations, 21%. (58%). Through the correlation analysis, etd was significantly associated The total number of non evaluable (NE) samples was significantly to the presence of brain metastases, the neutrophil to lymphocyte ratio increased in 2020 compared to 2019 (p = .029). During 2019, 80% of and the adenocarcinoma histology. the NE samples could be evaluated by any multiplex technique. On the Conclusions: Matching data from AHFs and CRs may reliably map tmnt contrary, during 2020 only 54% of NE were tested by any NGS-based pathway with innovative drugs. Our analysis confirmed a prognostic method. impact of early N discontinuation and identified brain metastases, high Conclusions: Our results show that molecular diagnosis of LC could be neutrophil to lymphocyte ratio and the adenocarcinoma histology as preserved during the COVID 19 outbreak. However genomic service predictors of early tmnt interruption. disruptions during critical months of the pandemic clearly impacted in Legal entity responsible for the study: Veneto Oncology Network at the number of pts with a NE result and might explain the differences in Istituto Oncologico Veneto IRCCS Padua, Italy. the incidence of KRAS mutations observed. While this global crisis Funding: Regional finalized research funding RSF-2017-00000557. rightly demands the world’s attention, a continuous and accurate Disclosure: All authors have declared no conflicts of interest. molecular diagnostic testing must be ensured to guarantee quality-care for LC pts. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: C. Teixido: Honoraria (self ), Personal fees: Pfizer; Honoraria (self ), Personal fees: Novartis; Honoraria (self ), Personal fees: Takeda; Honoraria (self ), Personal fees: MSD; Honoraria (self ), Personal fees: Roche; Honoraria (self ), Personal fees: Diaceutics; Honoraria (self ), Personal fees: AstraZeneca; Research grant/Funding (self ), Research funding: Pfizer; Research grant/Funding (self ), Research funding: Novartis. R. Reyes: Honoraria (self ), Speaker Honoraria: Roche; Honoraria (self ), Speaker Honoraria: MSD. L. Mezquita: Honoraria (self ), Speaker Honoraria: Bristol-Myers Squibb; Honoraria (self ), Speaker Honoraria: Tecnofarma; Honoraria (self ), Speaker Honoraria: Roche; Honoraria (self ), Speaker Honoraria: Takeda; Advisory/Consultancy: Roche Diagnostics; April 2021 Abstracts S797

Advisory/Consultancy: Takeda; Advisory/Consultancy: Roche; Travel/ and didn’t differ in men and women (p = 0,71). 1- and 5-year survival Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/ were 48.9% and 20%, respectively. Expenses: Roche; Research grant/Funding (self ): Amgen; Research grant/ Funding (self ): Bristol-Myers Squibb; Research grant/Funding (self ): Conclusions: Pulmonary CS are rare aggressive tumors, developing Boehringer Ingelheim; Speaker Bureau/Expert testimony, Mentorship program predominantly in elderly men. In a small subset of patients long-term with key opinion leaders: AstraZeneca. N. Reguart: Honoraria (self ), Speaker survival can be achieved. Honoraria: MSD; Honoraria (self ), Speaker Honoraria: BMS; Honoraria (self ), Legal entity responsible for the study: The authors. Speaker Honoraria: Roche; Honoraria (self ), Speaker Honoraria: Boehringer Ingelheim; Honoraria (self ), Speaker Honoraria: Guardant Health; Honoraria Funding: Has not received any funding. (self ), Speaker Honoraria: Pfizer; Honoraria (self ), Speaker Honoraria: AbbVie; Disclosure: All authors have declared no conflicts of interest. Honoraria (self ), Speaker Honoraria: Ipsen; Honoraria (self ), Speaker Honoraria: Novartis; Honoraria (self ), Speaker Honoraria: AstraZeneca; Honoraria (self ), Speaker Honoraria: Lilly; Honoraria (self ), Speaker Honoraria: Takeda; Honoraria (self ), Speaker Honoraria: Amgen; Honoraria (self ), Organization of educational 184P events: Amgen; Honoraria (self ), Organization of educational events: Roche; Bone-targeted agents (BTA)improve survival in advanced non- Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: small cell lung cancer (aNSCLC) patients (pts) with high bone Roche; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AbbVie; tumor burden (HBTB) treated with PD-(L)-1 inhibitors (ICIs) Advisory/Consultancy: Ipsen; Advisory/Consultancy: Novartis; Advisory/ Consultancy: AstraZeneca; Advisory/Consultancy: Lilly; Advisory/Consultancy: S. Manglaviti1, G. Galli1, M. Bini1, A. Labianca1, E. Zecca2, Takeda; Advisory/Consultancy: Amgen; Travel/Accommodation/Expenses: 1 1 1 1 1 Boehringer Ingelheim; Travel/Accommodation/Expenses: MSD; Travel/ M. Brambilla , M. Occhipinti , C. Proto , A. Prelaj , D. Signorelli , 1 1 1 1 1 Accommodation/Expenses: Roche; Research grant/Funding (self ): Novartis; A. De Toma , G. Viscardi , T. Beninato , E. Zattarin , M. Ganzinelli , Research grant/Funding (self ): Pfizer. All other authors have declared no conflicts F.G.M. de Braud1, M.C. Garassino1, G. Lo Russo1, R. Ferrara1 1Medical of interest. Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 2Palliative Care, Pain Therapy and Rehabilitation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 183P Background: BTA prevent skeletal-related events in cancer pts treated Pulmonary carcinosarcomas: A retrospective analysis of cases with chemotherapy (CT) with no significant impact on overall survival from cancer registry (OS). Among BTA, denosumab (DN) improved OS compared to zoledronic acid (ZA) in a subgroup analysis of aNSCLC pts with bone M. Puchinskaya1, L. Levin2 1Out-Patient Department, Minsk City Clinical 2 metastases (BM), while in the SPLENDOUR trial the addition of DN to Oncologic Dispensary, Minsk, Belarus; N. N. Alexandrov National Cancer 1st-line CT in aNSCLC did not improve survival. Currently, the impact of Centre of Belarus, Lesnoy, Belarus BTA in ICI treated aNSCLC with BM is unclear. – Background: Carcinosarcomas (CS) are rare malignant biphasic tumors, Methods: Data from aNSCLC pts with BM treated with ICIs (03/2013 that may arise in any organ. In recent years the process of epithelial- 06/2020) in one institution were retrospectively collected. BTA therapy − mesenchymal transition has been implicated in their development – a was defined as treatment with DN or ZA administered 60/+30 days notion, that may change treatment options for patients. Here we aimed to from ICI start and pursued concurrently. HBTB was defined as presence ≥ analyze some features of lung CS from the country-wide population of 3 BM. Median OS (mOS) and progression-free survival (mPFS) were cancer registry. estimated with Kaplan-Meier and multivariate analysis was performed Methods: A retrospective search in Belarusian cancer registry database by Cox proportional hazards regression model. was performed using the criteria: “histological diagnosis code: 8980/3” Results: 161 pts were included, 78 (48%) received BTA. Overall, BTA did – and “location code: C34.”All the data found were manually reviewed for not significantly prolong mOS [7.8 months (m) (CI 95% 4.6 10.9) vs – – the accordance to search criteria. Clinical data, treatment options and 6.8 m (95% CI 3.6 9.9), p = 0.83] or mPFS [2.9 m (95% CI 2.3 3.6) vs – outcomes were analyzed for all patients. No formal review of the slides 2.1 m (95% CI 1.8 2.3), p = 0.84]. HBTB group included 85 pts: 16 was performed. (19%) received DN, 29 (35%) ZA, 40 (46%) did not receive any BTA. In – Results: 45 cases of pulmonary CS were diagnosed in 1995–2016, those HBTB pts, BTA significantly improve mOS [7.8 m (95% CI 3.5 12) vs – – being the most frequent non-gynaecological CS. The majority of patients 3.5 m (95% CI 2.9 4), p = 0.01] and mPFS [2.6 m (95% CI 1.9 3.3) vs – (n = 40, 88.9%) were men. Median age at diagnosis was 67 (47–84) 1.8 m (95% CI 1.5 2.1), p = 0.002). BTA associated benefit in OS [HR – – years. Tumor was located in the left lung in 16 (35.6%), right in 29 0.59 (95% CI 0.35 0.90), p = 0.02] and PFS [HR: 0.53 (95% CI 0.32 (64.4%). Major bronchus was affected in 1 (2.2%) case, lobar bronchi in 0.83, p = 0.006) was confirmed at multivariate analysis adjusting for PS, 18 (40.0%), peripheral tumors were seen in 20 (44.4%) patients, in 2 number of metastatic sites, therapy line, BM radiotherapy. In HBTB pts, – – (4.4%) cases tumor location was not clearly stated. Regional lymph node ZA did not prolong mOS [3.8 m (95% CI 0.3 7.3) vs 3.8 m (95% CI 2.6 metastases at presentation were seen in 7 (15.6%) patients. The disease 5.0), p = 0.70], while DN significantly improve both mPFS [2.6 m (95% – – was diagnosed in stage I in 14 (31.1%) cases, II – in 8 (17.8%), III – in 11 CI 0.6 4.6) vs 1.8 m (95% CI 1.5 2.1), p = 0.02] and mOS [15.1 m (95% – – (24.4%), IV – in 6 (13.3%). Disease progression developed in 17 (37.8%) CI 0.1 33.1) vs 3.8 (95% CI 2.6 5.0), p = 0.01] compared to no-BTA. cases. Median progression free survival was 20 months, not differing for Conclusions: In ICI-treated aNSCLC with BM, BTA did not impact on men and women (p = 0,68). Metastases developed in lungs and bones survival. However, in HBTB subgroup BTA significantly improved PFS (n = 7, 15.6%), brain (n = 6, 13.3%), lymph nodes (n = 5, 11.1%), liver and OS, making these pts the best candidates for BTA-ICI concurrent (n = 3, 6.7%), pleura, adrenals (n = 2, 4.4%), pericardium, diaphragm, treatment. DN rather than ZA was associated with survival benefit, stomach, soft tissues, spine in single patients. Surgical treatment suggesting a synergy between ICI and RANK ligand inhibition. (including palliative) was used in 42 (93.3%) cases, radiotherapy Legal entity responsible for the study: Fondazione IRCCS Istituto alone in 1 (2.2%), chemotherapy alone in 2 (4.4%). 28 (62.2%) patients Nazionale dei Tumori. died of the disease, 5 (11.1%) more died of other causes, 12 (26.7%) Funding: Has not received any funding. were alive at the time of analysis. Median overall survival was 20 months Disclosure: All authors have declared no conflicts of interest. S798 Journal of Thoracic Oncology Vol. 16 No. 4S

Research grant/Funding (self ), Travel/Accommodation/Expenses, clinical trial research: Pfizer; Honoraria (self ), Advisory/Consultancy, Travel/Accommodation/ 185TiP Expenses: PrIME Oncology; Advisory/Consultancy, Research grant/Funding (self ), A phase Ib dose-escalation study evaluating trastuzumab Travel/Accommodation/Expenses, clinical trial research: Roche; Honoraria (self ), deruxtecan (T-DXd) and durvalumab in combination with Advisory/Consultancy: Peer CME; Research grant/Funding (self ), clinical trial research: MedImmun; Research grant/Funding (self ), clinical trial research: chemotherapy as first-line treatment in patients with Sanofi-Aventis; Research grant/Funding (self ), clinical trial research: Taiho advanced or metastatic nonsquamous non-small cell lung Pharma; Research grant/Funding (self ), clinical trial research: Novocure. J.C-H. cancer (NSCLC) and HER2 overexpression (DESTINY-Lung03) Yang: Advisory/Consultancy, Lecture: Boehringer Ingelheim; Advisory/ Consultancy: Eli Lilly; Advisory/Consultancy: Bayer; Advisory/Consultancy, 1 2 3 4 5,8 Lecture: Roche/Genentech; Advisory/Consultancy, Lecture: Chugai D. Planchard , J.C-H. Yang , J.R. Brahmer , A. Ragone , J. Chen , Pharmaceutical; Advisory/Consultancy, Lecture: MSD; Advisory/Consultancy, 6 7 1 F. Liu , M. Saggese Department of Medical Oncology, Thoracic Unit, Lecture: Pfizer; Advisory/Consultancy, Lecture: Novartis; Advisory/Consultancy, Gustave Roussy, Villejuif, France; 2Department of Medical Oncology, Lecture: BMS; Advisory/Consultancy: Ono Pharmaceutical; Advisory/Consultancy, National Taiwan University Cancer Center, Taipei City, Taiwan; 3The Johns Lecture: AstraZeneca; Advisory/Consultancy: Merck Serono; Advisory/ 4 Consultancy: Yuhan Pharmaceutical; Advisory/Consultancy: Daiichi Sankyo; Hopkins University, Baltimore, MD, USA; Late Development, Oncology Advisory/Consultancy: Hansoh Pharmaceutical; Advisory/Consultancy, Lecture: 5 R&D, AstraZeneca Pharmaceuticals LP, Mississauga, AB, Canada; Late Takeda Oncology; Advisory/Consultancy: Amgen. J.R. Brahmer: Advisory/ Development, Oncology R&D, AstraZeneca Pharmaceuticals LP, Consultancy, Research grant/Funding (institution): AstraZeneca. A. Ragone: Gaithersburg, MD, USA; 6Oncology Biometrics, AstraZeneca Research grant/Funding (self ), Medical Scientist for DESTINY-Lung03ng03: 7 AstraZeneca. J. Chen: Research grant/Funding (self ), Recipient of the AACR/ Pharmaceuticals LP, Gaithersburg, MD, USA; Late Development, Oncology AstraZeneca Clinical Immuno-Oncology Research Fellowship: AstraZeneca; 8 R&D, AstraZeneca Pharmaceuticals LP, Cambridge, UK; University of Research grant/Funding (self ), Funding for the AACR/AstraZeneca Clinical California Davis, Sacramento, CA, USA Immuno Oncology Research Fellowship is paid through AACR grant: AACR. F. Liu: Full/Part-time employment: AstraZeneca. M. Saggese: Full/Part-time Background: In patients (pts) with metastatic NSCLC without EGFR/ employment: AstraZeneca LP. ALK/ROS1 genomic aberrations, platinum doublet chemotherapy (ctx) + anti–PD-1/L1 immunotherapy is the current first-line standard of care. HER2 overexpression, an established target for treatments in breast and 186TiP gastric cancers, is observed in up to 30% of pts with NSCLC. T-DXd is an An open-label, dose escalation, phase I/II study to assess antibody-drug conjugate consisting of an anti-HER2 antibody, a cleavable safety, tolerability, immunogenicity and preliminary clinical tetrapeptide-based linker, and a membrane-permeable topoisomerase I activity of the therapeutic cancer vaccine PDC*lung01 with or inhibitor payload. In pts with heavily pretreated HER2-overexpressing or without anti-programmed death-1 (PD-1) treatment in -mutated NSCLC, T-DXd showed promising antitumor activity, with patients with non-small cell lung cancer (NSCLC) responses in 10/18 pts (56%; Tsurutani J et al. Cancer Discov. 2020). Here we describe the DESTINY-Lung03 trial (NCT04686305) evaluating J. Bennouna1, A. Sibille2, C. Debruyne3, B. Colinet4, I. Demedts5, T-DXd + durvalumab (durva; anti–PD-L1 immunotherapy) + ctx as first- 6 7 8 9 10 S. Derijcke , L. Greillier ,J.Jürgens , H. Lena , D. Moro-Sibilot , line treatment in pts with HER2-overexpressing NSCLC. M. Perol11, X. Quantin12, N. Reinmuth13, M. Sebastian14, M. Genin15, Trial design: This is an open-label, multicenter, phase Ib study in pts 16 17 1 J. Plumas , J.F. Vansteenkiste Thoracic Oncology Unit, University with HER2-overexpressing (immunohistochemistry 3+ or 2+) locally Hospital of Nantes, Nantes, France; 2Department of Pulmonology, Centre advanced or metastatic nonsquamous NSCLC without EGFR/ALK/ROS1 Hospitalier Universitaire Sart Tilman, Liege,̀ Belgium; 3Clinical genomic aberrations who are treatment naive in the metastatic setting. 4 Department, PDC*line Pharma SA, Liege,̀ Belgium; Pneumology and The trial consists of a safety run-in of ≥6 pts treated with T-DXd + durva, Oncology unit, Grand Hôpital de Charleroi (GHdC), Charleroi, Belgium; followed by a dose-escalation phase of T-DXd + durva + ctx and an 5Department of Pulmonary Diseases, AZ Delta, Roeselare, Belgium; optional dose expansion. In the dose-escalation phase, pts are 6Department of Thoracic Oncology/Pulmonology, AZ Groeninge Hospital, assigned per a modified toxicity probability interval design to T-DXd + Kortrijk, Belgium; 7Aix Marseille University, APHM, Marseille, France; durva + 1 of 3 ctx options: cisplatin (arm 1), carboplatin (arm 2), 8 9 Kliniken der Stadt Köln gGmbH, Cologne, Germany; CHU de Pontchaillou, pemetrexed (arm 3). Dose expansion of arms 1–3 (T-DXd + durva + ctx) Rennes, France; 10Thoracic Oncology, CHU de Grenoble, La Tronche, will be based on results from dose escalation. Pts in arm 4 will continue France; 11Department of Medical Oncology, Leoń Berard́ Cancer Centre, to receive T-DXd + durva following the safety run-in. Primary endpoints 12 Lyon, France; Oncology Department, Montpellier Cancer Institute, are safety of T-DXd + durva ± ctx and determination of the recom- Montpellier, France; 13Thoracic Oncology, Asklepios-Fachklinikum, mended phase II dose of T-DXd + durva + ctx. Secondary endpoints are 14 Gauting, Germany; Department of Hematology/Medical Oncology, confirmed objective response rate, disease control rate, duration of Universitätsklinikum Frankfurt (Johannes-Wolfgang Goethe Institute), response, progression-free survival (by investigator-assessed RECIST Frankfurt am Main, Germany; 15PDC*line Pharma SAS, La Tronche, v1.1), overall survival, pharmacokinetics, and immunogenicity. 16 17 France; R&D, PDC*Line Pharma, La Tronche, France; Respiratory Clinical trial identification: NCT04686305. Oncology Unit (Pulmonology), University Hospitals KU Leuven, Leuven, Editorial acknowledgement: Editorial writing support was provided Belgium by Michael Demars, PhD (Articulate Science LLC), which was funded by AstraZeneca Pharmaceuticals LP, Gaithersburg, MD, USA, in accordance Background: Anti-PD-1 antibodies are the cornerstone of treatment for with Good Publication Practice (GPP3) guidelines. advanced NSCLC. However, a substantial number of patients do not Legal entity responsible for the study: AstraZeneca Pharmaceuticals. benefit from PD-1 blockade when used in monotherapy. Boosting Funding: AstraZeneca Pharmaceuticals. antitumor cytotoxic CD8+ T cells represents a promising approach to Disclosure: D. Planchard: Honoraria (self ), Advisory/Consultancy, Research potentiate their efficacy. PDC*lung01 is a therapeutic cancer vaccine grant/Funding (institution), Travel/Accommodation/Expenses, clinical trial consisting in a plasmacytoid dendritic cell line (PDC*line), loaded with research: AstraZeneca; Honoraria (self ), Advisory/Consultancy, Research grant/ HLA-A*02:01 restricted peptides, and irradiated. The selected peptides Funding (institution), clinical trial research: Bristol-Myers Squibb; Honoraria (self ), Advisory/Consultancy, Research grant/Funding (self ), clinical trial are encoded by antigens expressed in NSCLC: NY-ESO-1, MAGE-A3, research: Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy: MAGE-A4, Multi-MAGE-A, MUC1, Survivin and Melan-A, used as a Celgene; Advisory/Consultancy, Research grant/Funding (self ), clinical trial positive control of PDC*lung01-induced immunogenicity. PDC*line is a research: Daiichi Sankyo; Honoraria (self ), Advisory/Consultancy, Research professional antigen presenting cell able to prime and expand peptide- grant/Funding (self ), clinical trial research: Eli Lilly; Honoraria (self ), Advisory/ Consultancy, Research grant/Funding (self ), clinical trial research: Merck; specific CD8+ T cells in vitro and in vivo, and is synergistic with anti-PD-1. Advisory/Consultancy, Research grant/Funding (self ), Travel/Accommodation/ Trial design: This is an open-label, multicentre, dose-escalation, phase Expenses, clinical trial research: Novartis; Honoraria (self ), Advisory/Consultancy, I/II study with PDC*lung01 administered by subcutaneous and April 2021 Abstracts S799 intravenous route weekly for 6 consecutive doses. Patients enrolled are aged ≥18 years, with NSCLC, performance status 0–1 and adequate bone 187TiP marrow/organ function. There are 4 cohorts: A1 (n = 6): NSCLC with Phase II, multicenter study of autologous tumor infiltrating 6 resected stage II/IIIA in adjuvant setting treated with low dose (14 × 10 lymphocytes (TIL, LN 144/LN-145/LN-145-S1) in patients with cells) PDC*lung01 vaccine as single agent following standard of care; A2 solid tumours (n = 10): same population as A1 with high dose (140 × 106 cells); B1 (n = 6): stage IV NSCLC with measurable disease, PD-L1 tumour proportion S. Gettinger1, H. Kluger1, A. Schoenfeld2, A. Betof Warner3,K.He4, score ≥50% and no driver mutation, treated with low dose vaccine A. Sukari5, S.S. Thomas6, B. Doger de Spéville7, S. Lee8, S. Haefliger9, added to anti-PD-1 treatment; B2 (n = 42): same population as B1 with Z. Goldberg10, A. Cacovean10, R. Fiaz10, G. Chen10, M. Jagasia10, high dose. Patients are pre-screened for HLA-A*02:01 positivity and F. Graf Finckenstein10, M. Fardis10, A. Jimeno11 1Yale Cancer Center, absence of antibodies against the HLA molecules expressed by PDC*line. Yale University School of Medicine, New Haven, CT, USA; 2Memorial Sloan Primary endpoint is to determine safety and tolerability of the two dose Kettering Cancer Center, New York, NY, USA; 3Medicine, Memorial Sloan levels. Ex-vivo evaluation of the immune response against antigens Kettering Cancer Center, New York, NY, USA; 4Medical Oncology, James borne by PDC*lung01 will be performed as secondary endpoint. Cancer Center, The Ohio State University, Columbus, OH, USA; 5Barbara Additional clinical endpoints of cohort B2 are response rate and 9- Ann Karmanos Cancer Center, Wayne State University, Detroit, MI, USA; month progression-free survival per RECIST v1.1 and iRECIST. Patient 6University of Florida Health Cancer Center at Orlando Health, Orlando, enrolment is ongoing. FL, USA; 7Start-Madrid Phase 1 Unit, University Hospital Fundacion Clinical trial identification: NCT03970746. Jimenez Diaz, Madrid, Spain; 8Seattle Cancer Care Alliance, University of Legal entity responsible for the study: PDC*line Pharma SAS. Washington, Seattle, Seattle, WA, USA; 9Inselspital, Universitätsspital Funding: PDC*line Pharma SAS. Bern, Bern, Switzerland; 10Iovance Biotherapeutics, Inc., San Carlos, CA, Disclosure: J. Bennouna: Advisory/Consultancy, Speaker Bureau/Expert testi- 11 mony: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, F. Hoffmann–La USA; University of Colorado Comprehensive Cancer Center, Aurora, Roche Ltd, MSD, Novartis; Honoraria (self ): AstraZeneca, Bayer, Boehringer CO, USA – Ingelheim, Bristol-Myers Squibb, F. Hoffmann La Roche Ltd, Merck, MSD, Novartis. + A. Sibille: Honoraria (self ), Advisory/Consultancy: AstraZeneca, Boehringer Background: TIL (especially CD8 T cells) in the tumor microenviron- Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer, Roche, ment is associated with survival outcomes in many solid tumors, Takeda. C. Debruyne: Full/Part-time employment: PDC*line Pharma SAS. including melanoma (Mel), head and neck squamous cell carcinoma I. Demedts: Honoraria (self ), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca, BMS, Boehringer, GSK, Lilly, MSD, Novartis, Pfizer, Roche (HNSCC), and non-small cell lung cancer (NSCLC). Lifileucel (LN-144), and Takeda. L. Greillier: Advisory/Consultancy, Speaker Bureau/Expert testimony: has shown efficacy with durable responses in advanced melanoma (Mel) AbbVie, BMS, Boehringer Ingelheim, AstraZeneca, Novartis, Pfizer, MSD, Takeda. (Sarnaik et al., ASCO 2020), metastatic cervical cancer (Jazaeri et al., H. Lena: Honoraria (self ), Advisory/Consultancy: AstraZeneca, Roche, MSD, BMS, ASCO 2019), and LN-145 + pembrolizumab in HNSCC (Jimeno et al., SITC Pfizer, Novartis, Amgen, Takeda. M. Perol: Honoraria (self ), Advisory/Consultancy: Roche, Genentech, Eli Lilly, Pfizer, Boehringer-Ingelheim, MSD, Bristol-Myers 2020). TIL therapy has shown evidence of efficacy in metastatic NSCLC Squibb, Novartis, AstraZeneca, Takeda, Gritstone, Sanofi; Research grant/Funding in a phase I study (Creelan et al., ASCO 2020). (institution): Roche, AstraZeneca, Chugai, Takeda, Boehringer Ingelheim; Honoraria (self ), Speaker Bureau/Expert testimony: Eli Lilly, Roche, AstraZeneca, Pfizer, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Takeda, MSD, Chugai, Illumina. N. Reinmuth: Honoraria (self ), Advisory/ Table 187TiP: IOV-COM-202 study design Consultancy, Speaker Bureau/Expert testimony: AstraZeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, Hoffmann-La Roche, MSD, Merck, Pfizer, and Cohorts Patient Population Sample Size Treatment Regimen Takeda. M. Sebastian: Research grant/Funding (self ): AstraZeneca; Honoraria (self ), Advisory/Consultancy: AstraZeneca, BMS, MSD, Sanofi, Tesaro, Cilag 1A Melanoma: PD-1/ N = 12 lifileucel/LN-144 + Janssen, Amgen, Pfizer, Novartis, Boehringer-Ingelheim, Takeda, Lilly, CureVac, PD-L1 naive pembrolizumab BionTech; Honoraria (self ), Speaker Bureau/Expert testimony: AstraZeneca, 1B Melanoma: ≥ 1 N = up to 27 LN-145-S1 as single Sanofi, Novartis, Boehringer-Ingelheim, Takeda. M. Genin: Full/Part-time employ- prior systemic agent ment: RLM Consulting SPRL. J. Plumas: Full/Part-time employment: PDC*line therapy(ies) Pharma SAS. J.F. Vansteenkiste: Research grant/Funding (institution): Merck Sharp 1C Melanoma: ≥ 1 N = up to 27 lifileucel/LN-144 as & Dohme; Advisory/Consultancy: AstraZeneca, Boehringer Ingelheim, Bristol prior systemic single agent Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi; Speaker therapy(ies) Bureau/Expert testimony: AstraZeneca, Eli-Lilly, Merck Sharp & Dohme. All other authors have declared no conflicts of interest. 2A HNSCC: PD-1/PD- N = 19 LN-145 + L1 naive pembrolizumab 3A NSCLC: PD-1/PD-L1 N = 12 LN-145 + naive pembrolizumab 3B NSCLC: ≥ 1 prior N = 12 LN-145 as single systemic therapy agent (ies) 3C NSCLC: 1 prior N = up to 26 LN-145 + systemic therapy ipilimumab & nivolumab

Trial design: IOV-COM-202 (NCT03645928) is a phase II global, open- label multi-cohort, non-randomized study designed to evaluate the safety and efficacy of TIL therapy as a single agent or in combination with immune checkpoint inhibitors. All patients receive either, lifileucel, LN- 145 or LN-145-S1 (PD-1 select TIL), which is manufactured at centralized GMP facilities generating a cryopreserved infusion product which is shipped to the treatment centers. Cohort 1, 2 and 3 enroll Mel, HNSCC and NSCLC patients, respectively (Table). Patients undergo a nonmyeloablative lymphodepletion (NMA-LD) regimen prior to TIL infusion, followed by up to 6 doses of intravenous IL-2. Patients in Cohorts 1A, 2A, and 3A start pembrolizumab following tumor harvest for TIL generation, but prior to NMA-LD. Pembrolizumab is dosed per label. S800 Journal of Thoracic Oncology Vol. 16 No. 4S

Patients in Cohorts 1B, IC and 3B receive LN-145-S1, lifileucel, and LN- Trial design: IOV-LUN-202 (NCT04614103) is a prospective, open- 145, respectively. Cohort 3C patients receive a dose of ipilimumab and label, multi-cohort, non-randomized, multicenter phase II study. Patient nivolumab prior to tumor harvest, with nivolumab continuing Q4W for cohorts (n = 40 ea.) based on tumor proportion score (TPS) at metastatic up to 2 years, or until progression or unacceptable toxicity. Key eligibility diagnosis prior to ICI use are Cohort 1 (TPS <1%) and Cohort 2 (TPS ≥ includes: ≥ 18 years of age; RECIST measurable disease; ≥ 1 lesion(s) 1%). Cohort 3 (TPS <1%; n = 15), utilizes core biopsies for tumor available for TIL generation; ECOG PS 0–1. The primary endpoint: ORR acquisition for patients unable to undergo a surgical harvest. LN-145 is per RECIST v1.1. Secondary endpoints: safety, CR rate, DOR, DCR, PFS, generated at centralized GMP facilities and the final cryopreserved and OS. infusion product is shipped to the sites. All patients receive TIL therapy Clinical trial identification: NCT03645928. consisting of nonmyeloablative lymphodepletion with cyclophospha- Legal entity responsible for the study: Iovance Biotherapeutics, Inc. mide (60 mg/kg × 2) + fludarabine (25 mg/m2 × 5), followed by a single Funding: Iovance Biotherapeutics, Inc. infusion of autologous LN-145 (Day 0) and up to 6 doses of IL-2 Disclosure: A. Betof Warner: Honoraria (self ): LC Chem Life Sciences; Advisory/ (600,000 IU/kg). Key eligibility includes: ≥18 y of age; 1 prior line of Consultancy: Nanobiotix; Advisory/Consultancy: Novartis; Advisory/Consultancy: therapy; ≥ 1 lesion(s) available for TIL generation and a remaining Iovance. S.S. Thomas: Honoraria (self ), Speaker Bureau/Expert testimony: BMS; RECIST-measurable lesion; and ECOG PS of 0–1. For each cohort, the Honoraria (self ), Speaker Bureau/Expert testimony: Merck; Honoraria (self ), Speaker Bureau/Expert testimony: Amgen; Honoraria (self ), Speaker Bureau/ primary endpoint is ORR per RECIST 1.1. Secondary endpoints are Expert testimony: Ipsen; Honoraria (self ), Speaker Bureau/Expert testimony: safety, CR rate, DOR, DCR, PFS, OS and efficiency of generating LN-145 Pfizer; Honoraria (self ), Speaker Bureau/Expert testimony: Novartis; Honoraria from tumor core biopsies (Cohort 3). (self ), Speaker Bureau/Expert testimony: Genentech; Honoraria (self ), Speaker Bureau/Expert testimony: Array. S. Lee: Travel/Accommodation/Expenses: Iovance; Licensing/Royalties: Fred Hutchinson. S. Haefliger: Shareholder/ Table 188TiP: IOV-LUN-202 patient cohorts Stockholder/Stock options: Celgene; Advisory/Consultancy: Bayer; Advisory/ Consultancy: Eli Lilly; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Patient Population Merck. Z. Goldberg: Shareholder/Stockholder/Stock options, Licensing/Royalties, Metastatic NSCLC without an actionable driver mutation Full/Part-time employment: Iovance. A. Cacovean: Travel/Accommodation/ and progressive disease on or following a single line of Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: approved systemic therapy including ICI + Chemo ± Iovance. R. Fiaz: Shareholder/Stockholder/Stock options, Full/Part-time employ- Cohort Bevacizumab Sample Size ment: Iovance; Shareholder/Stockholder/Stock options: AbbVie. G. Chen: Shareholder/Stockholder/Stock options, Full/Part-time employment: Iovance. 1 PD-L1 TPS <1% N = 40 M. Jagasia: Shareholder/Stockholder/Stock options, Full/Part-time employment: 2 PD-L1 TPS ≥1% N = 40 Iovance. F. Graf Finckenstein: Leadership role, Travel/Accommodation/Expenses, 3 PD-L1 TPS <1%/Core Biopsies N = 15 Full/Part-time employment: Iovance; Shareholder/Stockholder/Stock options: 4 Retreatment N = undefined Roche/Genentech; Shareholder/Stockholder/Stock options: BMS. M. Fardis: Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/ Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/ Part-time employment, Officer/Board of Directors: Iovance; Shareholder/ Clinical trial identification: NCT04614103. Stockholder/Stock options: Gilead; Shareholder/Stockholder/Stock options: Legal entity responsible for the study: Iovance Biotherapeutics, Inc. AbbVie; Officer/Board of Directors: Kartos. A. Jimeno: Shareholder/Stockholder/ Funding: Iovance Biotherapeutics, Inc. Stock options: Champions Oncology; Shareholder/Stockholder/Stock options: Disclosure: E. Massarelli: Advisory/Consultancy, Speaker Bureau/Expert Gilead; Licensing/Royalties: SuviCca; Research grant/Funding (institution): BMS; testimony, Research grant/Funding (self ): Merck; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Research grant/Funding (institu- Research grant/Funding (self ): Genentech; Speaker Bureau/Expert testimony, tion): AstraZeneca; Research grant/Funding (institution): SQZ; Research grant/ Research grant/Funding (self ): AstraZeneca; Research grant/Funding (self ): BMS; Funding (institution): Cantaria; Research grant/Funding (institution): Merck; Research grant/Funding (self ): Pfizer; Research grant/Funding (self ): GSK; Research grant/Funding (institution): Iovance; Research grant/Funding (institu- Research grant/Funding (self ): Loxo; Research grant/Funding (self ): Spectrum. tion): Genocea; Research grant/Funding (institution): Khar; Research grant/ Z. Goldberg: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock Funding (institution): Debiopharm. All other authors have declared no conflicts of options, Full/Part-time employment: Iovance. A. Cacovean: Travel/ interest. Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part- time employment: Iovance. B. Yadav: Full/Part-time employment: Iovance. G. Chen: Shareholder/Stockholder/Stock options, Full/Part-time employment: Iovance. M. Jagasia: Shareholder/Stockholder/Stock options, Full/Part-time 188TiP employment: Iovance. F. Graf Finckenstein: Leadership role, Shareholder/ A phase II multicenter study of autologous tumor infiltrating Stockholder/Stock options, Full/Part-time employment: Iovance; Shareholder/ Stockholder/Stock options: Roche/Genentech; Shareholder/Stockholder/Stock lymphocytes (TIL, LN-145) cell therapy in patients with options: BMS. M. Fardis: Speaker Bureau/Expert testimony, Leadership role, metastatic non-small cell lung cancer (mNSCLC) Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment, Officer/Board of Directors: E. Massarelli1, Z. Goldberg2, A. Cacovean2, B. Yadav2, G. Chen2, Iovance; Shareholder/Stockholder/Stock options: Gilead; Shareholder/ 2 2 2 3 1 Stockholder/Stock options: AbbVie; Officer/Board of Directors: Kartos. All other M. Jagasia , F. Graf Finckenstein , M. Fardis , A. Sukari City of Hope authors have declared no conflicts of interest. Comprehensive Cancer Center, Duarte, CA, USA; 2Iovance Biotherapeutics, Inc., San Carlos, CA, USA; 3Barbara Ann Karmanos Cancer Center, Wayne State University, Detroit, MI, USA 189TiP Background: Patients with mNSCLC without actionable driver mutation Phase IV trial of afatinib followed by osimertinib versus (s) who have progressed after cytotoxic chemotherapy plus immune osimertinib alone as first-line treatment in patients (pts) with checkpoint inhibitors (ICI) ± bevacizumab have limited treatment advanced EGFR mutation-positive (EGFRm+) NSCLC options and represent an unmet need. The safety and efficacy of TIL cell therapy for mNSCLC patients who failed to respond or progressed on T. Wehler1, B. Wehler1, H. Atmaca-Dirik1, C. Schulz2, C. Grohé3, nivolumab has been evaluated in a phase I clinical trial (Creelan B. AACR J. Topsch4, A. Ehrlich4 1Evangelisches Krankenhaus Hamm & 2020), demonstrating an objective response rate (ORR) of 25% including Lungenklinik Hemer, Hamm, Germany; 2University Hospital Regensburg, 17% durable CRs. This provides a clear rationale for initiation of IOV- Regensburg, Germany; 3Evangelische Lungenklinik, Berlin, Germany; LUN-202 study, evaluating Iovance Gen 2 TIL cell therapy with LN-145 in 4Interdisciplinary Center Clinical Trials (IZKS), University Medical Center patients with mNSCLC without actionable driver mutation(s), who have Mainz, Mainz, Germany progressed on or following a single line of approved systemic therapy consisting of combined ICI + chemotherapy ± bevacizumab. Background: Tyrosine kinase inhibitors (TKIs) are the standard first- line treatment for pts with advanced EGFRm+ NSCLC. However, acquired resistance is inevitable, making subsequent therapy options a key April 2021 Abstracts S801 consideration. The T790M mutation in exon 20 of EGFR is the most common resistance mechanism to the second-generation TKI afatinib. 190TiP The third-generation TKI osimertinib has shown efficacy in pts with Anlotinib plus carboplatin/pemetrexed in treatment-naïve T790M-positive (T790M+) NSCLC. Consequently, a sequential treatment advanced non-squamous NSCLC: An open-label, randomized, strategy of afatinib followed by osimertinib has been proposed for pts phase II study who develop T790M. This sequential approach was associated with a median time on EGFR TKI treatment of 27.7 months in the observational R. Guo, W. Gao, J. Li, Y. Liu, X. Liu Oncology Department, Jiangsu GioTag study but has not been assessed in a prospective clinical trial. Province Hospital/The First Affiliated Hospital of Nanjing Medical Trial design: This randomised, multicentre phase IV trial University, Nanjing, China (NCT04413201) assesses sequential afatinib followed by osimertinib in pts who develop T790M, versus osimertinib alone. Eligible pts have Background: Anlotinib, an oral multi-targeted tyrosine kinase receptor stage IIIb/IV EGFRm+ NSCLC not eligible for radiochemotherapy (Del19 inhibitor, monotherapy improves OS and PFS as a third-line treatment or L858R mutations; pts with T790M+ at study entry are excluded). Pts for stage IV NSCLC. Bevacizumab added to paclitaxel/carboplatin is a have ECOG PS 0–2 and should have received no prior therapy. Pts with standard first-line therapy for advanced non-squamous NSCLC. Previous stable brain metastases may be included. Pts will be randomised 2:1 to study has explored the efficacy and safety of anlotinib in combination receive afatinib or osimertinib. Following progression, T790M+ pts in with chemotherapy as first-line therapy in advanced NSCLC patients. the afatinib arm will receive subsequent osimertinib, while T790M- This is the first trial evaluating the combination of chemotherapy and negative pts will receive investigator choice of therapy (ICT); all pts in anlotinib in treatment-naïve advanced non-squamous NSCLC. the osimertinib arm will receive ICT after progression. The primary Trial design: This was an open-label, randomized, phase II trial. Eligible endpoint is time to TKI treatment failure within 24 months for afatinib patients were adults with untreated non-squamous NSCLC, with ECOG followed by osimertinib in T790M+ pts versus osimertinib. Secondary PS 0 or 1 and at least one measurable lesion per Response Evaluation endpoints include time to TKI failure, PFS from start of TKI treatment to Criteria in Solid Tumors (version 1.1). All the patients receive 4–6 cycles progression after second-line therapy, overall survival, response rate and of carboplatin (area under curve 5 mg/mL per min) plus pemetrexed disease control rate. Pt-reported outcomes and safety will also be (500 mg/m2) plus anlotinib (12 mg per day, per os; days 1–14; 21 days assessed. Biomarker analysis will monitor the development of the per cycle). who had a response or stable disease were followed by T790M resistance mutation and examine biomarkers at the start of maintenance therapy. 90 pts were randomly assigned (in a 1:1:1 ratio) to treatment and after progression on afatinib or osimertinib. The trial pemetrexed; anlotinib; or both for up to disease progression. The began in June 2020; recruitment is ongoing at eight sites in Germany. An primary endpoint is PFS (time from the first day of anlotinib to the date estimated 126 pts will be enrolled. of disease progression or death from any cause, whichever occurred Clinical trial identification: NCT04413201, first posted June 2, 2020. first). Secondary endpoints include OS, ORR, DCR, quality of life and Editorial acknowledgement: Medical writing assistance, supported safety profile. Clinical trial information: NCT04453423. financially by Boehringer Ingelheim, was provided by Jim Sinclair, PhD, Clinical trial identification: NCT04453423. of GeoMed, an Ashfield company, part of UDG Healthcare plc, during the Legal entity responsible for the study: The authors. development of this abstract. Funding: Has not received any funding. Legal entity responsible for the study: Michael Hopp, Head of Disclosure: All authors have declared no conflicts of interest. Interdisciplinary Center for Clinical Studies (IZKS), Johannes Gutenberg University Mainz. Funding: Boehringer Ingelheim. 191TiP Disclosure: T. Wehler: Honoraria (self ), Advisory/Consultancy, Research grant/ Funding (institution), Honoraria, Consulting fees, Corporate-sponsored research: Accelerating lung cancer diagnosis through liquid biopsy Boehringer Ingelheim; Honoraria (self ), Advisory/Consultancy, Research grant/ Funding (institution), Honoraria, Consulting fees, Corporate-sponsored research: M. Garcıá Pardo de Santayana1, K. Czarnecka2, T. Waddell2, Roche; Honoraria (self ), Advisory/Consultancy, Research grant/Funding (institu- T. Stockley3,J.Law1, L.W. Le4,P.Pal5, P. Rogalla6, D.C. Kelly1, tion), Honoraria, Consulting fees, Corporate-sponsored research: Eli Lilly; 1 1 Honoraria (self ), Advisory/Consultancy, Research grant/Funding (institution), N. Leighl Medical Oncology Department, University Health Network - 2 Honoraria, Consulting fees, Corporate-sponsored research: Novartis; Honoraria Princess Margaret Cancer Center, Toronto, ON, Canada; Division of (self ), Advisory/Consultancy, Research grant/Funding (institution), Honoraria, Thoracic Surgery, Toronto General Hospital, Toronto, ON, Canada; Consulting fees, Corporate-sponsored research: Merck Sharp & Dohme; Honoraria 3Division of Clinical Laboratory Genetics, Laboratory Medicine Program, (self ), Advisory/Consultancy, Research grant/Funding (institution), Honoraria, 4 Consulting fees, Corporate-sponsored research: Bristol Myers Squibb; Honoraria University Health Network, Toronto, ON, Canada; Department of (self ), Advisory/Consultancy, Research grant/Funding (institution), Honoraria, Biostatistics, University Health Network - Princess Margaret Cancer Consulting fees, Corporate-sponsored research: AstraZeneca; Honoraria (self ), Center, Toronto, ON, Canada; 5Department of Laboratory Medicine and Advisory/Consultancy, Research grant/Funding (institution), Honoraria, Pathology, University Health Network, Toronto, ON, Canada; 6Joint Dept. Consulting fees, Corporate-sponsored research: Pfizer; Honoraria (self ), Advisory/Consultancy, Research grant/Funding (institution), Honoraria, Medical Imaging, University Health Network, Toronto General Hospital, Consulting fees, Corporate-sponsored research: Takeda. B. Wehler: Advisory/ Toronto, ON, Canada Consultancy: Boehringer Ingelheim. C. Schulz: Honoraria (self ), Advisory/ Consultancy: Boehringer Ingelheim; Honoraria (self ), Advisory/Consultancy: Background: For patients with advanced non-small cell lung cancer AstraZeneca. C. Grohe:́ Honoraria (self ), Advisory/Consultancy, Speaker Bureau/ (NSCLC), outcomes are directly impacted by time from symptom onset to Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim. All treatment initiation. Wait times are long in lung cancer, given the limited other authors have declared no conflicts of interest. access to invasive diagnostic procedures as EBUS or CT-guided lung biopsy. With the current challenges of the COVID-19 pandemic, these wait times are even longer. Molecular profiling of tumor tissue is the gold standard for lung cancer diagnosis in patients with advanced disease. However, results are often delayed due profiling turnaround times, insufficient tissue samples and the need for repeat biopsies ∼10% of patients. Liquid biopsy, used to detect circulating tumor DNA in blood, is a minimally invasive method to obtain molecular profiling, is faster and potentially less expensive than repeat tumor biopsy. Trial design: This pilot study assesses the utility of liquid biopsy to accelerate the time to treatment for clinically selected patients with S802 Journal of Thoracic Oncology Vol. 16 No. 4S advanced NSCLC. We hypothesize that wait times for treatment initiation Ospedale Policlinico San Martino, Department of Internal Medicine and could be reduced by at least 50% (∼4–6 weeks) compared to the current Medical Specialties (DiMI), University of Genova, Genoa, Italy standard process of tissue biopsy and testing. We will recruit 40 patients Background: Brain metastases are one of the most important metastatic with a smoking history <=15 pack year, referred to the Princess Margaret Lung Cancer Rapid Assessment & Management Program, with radiologic lesions of advanced NSCLC patients and their incidence is higher in oncogene-addicted patients compared to wild-type ones. Despite the evidence of advanced (stage IV) lung cancer. Consenting patients will improvement of intracranial response and disease control observed with undergo peripheral blood draw and mutation profiling using a next generation sequencing (NGS) panel allowing for detection of the full target therapy, brain metastases are still one of the main negative prognostic factors associated with therapeutic failure and worse quality range of actionable targets in NSCLC. Testing of diagnostic tumor tissue will also be performed as per standard of care. Patients will receive an of life. The radiological and radiomic study of the primary tumor and metastatic lesions is one of the most promising areas of cancer research, expedited referral to medical oncology based on liquid biopsy results. not only for their diagnostic implication but also for their potential Molecular profiling results from blood and tumor will be recorded. Result turnaround time (95% CI), time to treatment initiation (95% CI), prognostic and predictive role in many tumor types, including lung cancer. In literature, some data are available on primary brain tumors, identification and comparison of actionable targets in both molecular and tumor profiling results, and patient outcomes will be analyzed. but scarce data are available on brain metastases from NSCLC. The Enrollment began in January, 2021. identification of specific radiological and radiomic features of brain metastases correlated with oncogene-addicted NSCLC could be a useful Legal entity responsible for the study: The authors. Funding: Lung Health Foundation. diagnostic and prognostic tool in clinical practice. Trial design: The BRAIN Lung is an ongoing multicentric retrospective Disclosure: N. Leighl: Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/ study conducted on advanced NSCLC patients with brain metastases Accommodation/Expenses: Amgen, Array Pharmaceuticals, AstraZeneca, divided into two cohorts: oncogene-addicted and wild-type patients. Boehringer Ingelheim, Bristol Myers Squibb, EMD Serono, Xcovery, Guardant Radiological images from magnetic resonance imaging and computed Health, Lilly, MSD, Pfizer, Roche, Takeda, and Teva. All other authors have declared tomography scans of the brain are collected at the time of brain no conflicts of interest. metastases diagnosis (baseline) and during treatment (intracranial best response and progression) and are assessed according to Response Assessment in Neuro-Oncology criteria. The primary objective is the 192TiP identification of specific MF, RF and their inclusion in a “radiological/ Radiological morphological (MF) and radiomic features (RF) of radiomic signature,” in oncogene-addicted NSLC patients compared to brain metastases in oncogene-addicted advanced non-small wild-type ones. Secondary objectives include the assessment of the cell lung cancer (NSCLC) patients: Diagnostic implications and prognostic and predictive role of MF, RF and radiological/radiomic prognostic role (BRAIN Lung study) signature at baseline and their variation during treatment, according to their correlation with survival, systemic and intracranial response S.E. Rebuzzi1, L. Barletta2, E. Rosso2, M. Maddalo3, A. Signori4, outcomes in both cohorts. F. Catalano5, M. Grassi5, M. Tagliamento6, G. Rossi7, M.G. Dal Bello8, Legal entity responsible for the study: Medical Oncology 2, IRCCS G. Mazzaschi9, E. Barabino10, A. Fedeli11, M. Doni12, M. Tiseo13, Ospedale Policlinico San Martino. C. Genova14 1Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Funding: Has not received any funding. Martino, Department of Internal Medicine and Medical Specialties (DiMI), Disclosure: M. Tagliamento: Travel/Accommodation/Expenses: Roche; Travel/ University of Genova, Genoa, Italy; 2Unit of Neuroradiology, IRCCS Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/ 3 Expenses: AstraZeneca; Travel/Accommodation/Expenses: Takeda; Honoraria Ospedale Policlinico San Martino, Genoa, Italy; Department of Medical (self ): Novartis; Honoraria (self ): Amgen. G. Rossi: Honoraria (self ), Honoraria 4 Physics, University Hospital of Parma, Parma, Italy; Department of (institution): Bristol Meyer Squibb; Honoraria (self ), Honoraria (institution): Health Sciences, Section of Biostatistics, University of Genova, Genoa, Italy; Roche; Honoraria (self ), Honoraria (institution): Amgen; Honoraria (self ), 5Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genoa, Honoraria (institution): Janssen. M. Tiseo: Advisory/Consultancy, Speaker 6 Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Italy; Medical Oncology 2, IRCCS Ospedale Policlinico San Martino, Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/ Department of Internal Medicine and Medical Specialties (DiMI), Consultancy, Speaker Bureau/Expert testimony: Eli-Lilly; Advisory/Consultancy, University of Genova, Genoa, Italy; 7Department of Medical, Surgical and Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/ Experimental Sciences, University of Sassari, Ospedale “Padre Antero Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert ” 8 testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Micone , Genoa, Italy; Medical Oncology 2, IRCCS Ospedale Policlinico San MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/ 9 Martino, Genoa, Italy; Medical Oncology Unit, University Hospital of Funding (institution): Boehringer Ingelheim; Advisory/Consultancy, Speaker Parma, Parma, Italy; 10Interventional Angiography Unit, Ospedale Santa Bureau/Expert testimony: Otsuka; Advisory/Consultancy, Speaker Bureau/ Corona, Pietra Ligure, Italy; 11Electrical, Electronics and Expert testimony: Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre. C. Genova: Honoraria (self ), Honoraria (institution): Telecommunication Engineering and Naval Architecture Department AstraZeneca; Honoraria (self ), Honoraria (institution): Bristol-Myers Squibb; 12 (DITEN), University of Genova, Genoa, Italy; Molecular Diagnostic Unit, Honoraria (self ), Honoraria (institution): Merck-Sharp-Dohme; Honoraria (self ), IRCCS Ospedale Policlinico San Martino, Genoa, Italy; 13Medical Oncology Honoraria (institution): Boehringer-Ingelheim; Honoraria (self ), Honoraria Unit, University Hospital of Parma;, Department of Medicine and Surgery, (institution): Roche. All other authors have declared no conflicts of interest. University of Parma, Parma, Italy; 14UO Clinica di Oncologia Medica, IRCCS ABSTRACTS

cancers and matched metastatic N2 lymph nodes of 12 T1N2M0 NSCLC METASTASES TO AND FROM THE LUNG patients and performed proteomics analysis followed by the Gene ontology (GO), KEGG and cluster analysis. 193P Results: Among 35 T1N2M0 NSCLC patients, which accounted for Long-term survival in non-small cell lung cancer patients with 2.82% of all surgically NSCLC patients in out hospital during 2018 and 2019, 22 (62.9%) were male and 21 (60.0%) patients had a history of metachronous brain-only oligorecurrence who underwent smoking as well as 9 (25.7%) had a history of diabetes. It was worth definitive treatment noting that 80.0% of T1N2M0 NSCLC patients had primary cancer in the right lung, and more than half (62.9%) of pathological types were H. Kim, S. Park, H.A. Jung, J-M. Sun, S-H. Lee, J.S. Ahn, K. Park, adenocarcinoma. In the SEER database, we found that T1N2M0 patients M-J. Ahn Hematology-Oncology, Samsung Medical Center, Seoul, Republic accounted for 1.89% of all surgically lung cancer patients and it showed of Korea that the 3-year and 5-year survival rate of T1N2M0 patients was 37.3% Background: Metachronous brain-only oligorecurrence in patients with and 24.6%, respectively. Further proteomics analysis from 12 paired non-small cell lung cancer (NSCLC) is a rare event with favorable lymph node metastasis and primary lung cancers found 474 differently prognosis, but the clinical outcome has not been fully determined. We expressed proteins (338 up-regulation and 136 down-regulation). These “ retrospectively analyzed clinical outcomes and prognostic factors in differently expressed proteins were mainly enriched in Arp2/3 protein ”“ ” “ metachronous brain-only oligorecurrence in patients with NSCLC who complex, actin fiber binding and Arp2/3 complex-mediated actin ” underwent definitive treatment. nucleation by GO enrichment of cellular component, molecular function Methods: We reviewed 4,437 NSCLC patients without oncogenic driver and biological process. KEGG analysis also demonstrated that the mutations who underwent definitive treatment between 2008 and 2018. regulation of actin cytoskeleton was significantly enriched. Among them, we identified 327 patients who developed 1 to 5 brain Conclusions: Although the tumor size is small, the prognosis of metastases with or without systemic metastasis. Of the 327 patients, 71 T1N2M0 NSCLC patients is poor. The pathway related to the regulation of had metachronous oligo-brain metastasis without extracranial progres- actin cytoskeleton may be involved in the mediastinal lymph node sion and were treated with local therapy to the brain, while 17 had metastasis for these highly invasive population, which deserves further synchronous oligometastases. Clinical outcomes of overall survival (OS), experimental exploration. progression-free survival (PFS), and prognostic factors affecting OS were Legal entity responsible for the study: The author. analyzed. Funding: Has not received any funding. Results: Over 41.2 months of follow-up, the median OS was 38.9 months Disclosure: The author has declared no conflicts of interest. (95% CI, 21.8 to 56.1 months) in 71 patients. The 2-year OS rate was 67.8% and the 5-year OS rate was 33.1%. The median PFS was 25.5 months (95% CI, 12.2 to 14.4 months). The longest surviving patient 195P had a survival period of 115 months. Through multivariate analysis, Brain and heart in cancer patients: A population-based study ECOG ≥1 (hazard ratio: 5.85, 95% CI: 1.92 to 17.79, P = 0.002) and non- adenocarcinoma (hazard ratio: 2.51, 95% CI: 1.07 to 5.89, P = 0.03) were M. Safi1, M. Al-Radhi2, R. Kanesvaran3, D. Trapani4, S. Mazher5, associated with poor survival. There was no significant difference in OS M. Alnusaif6, A. Aldanakh7, S. Baldi8, Y. Moeed9, H. Al-Dubai10, between patients with local therapy and those with local plus systemic X. Sun11, X. Shan1, M. Ameen12, J. Liu1 1Oncology, First Affiliated therapy (18.5 vs. 34.7 months, P = 0.82). Clinical outcomes of OS Hospital of Dalian Medical University, Dalian, China; 2Urology, Second between synchronous and metachronous brain-only oligorecurrence Affiliated Hospital of Dalian Medical University, Dalian, China; 3Thoracic NSCLC patients were comparable. Oncology, Uro-Oncology, National Cancer Center Singapore, Singapore; Conclusions: Metachronous brain-only oligorecurrence NSCLC patients 4Oncology Department, Istituto Europeo di Oncologia, Milan, Italy; who underwent definitive treatment experienced long-term survival 5Medical Oncology, The University of Texas Southwestern Medical Center, with local therapy, highlighting the unique patient population. The role Dallas, TX, United States of America; 6Department of Neurology, First of systemic chemotherapy in this patient population requires further Affiliated Hospital of Dalian Medical University, Dalian, China; 7Urology, investigation. First Affiliated Hospital of Dalian Medical University, Dalian, China; Legal entity responsible for the study: The authors. 8Clinical Laboratory Diagnostics, Dalian Medical University, Dalian, Funding: Has not received any funding. China; 9Maternal and Child Health, Guangxi Medical University, Nannig, Disclosure: All authors have declared no conflicts of interest. China; 10Radiology, Eastern Cost Medical and Teaching Compound, Hodaidah, Yemen; 11Medical Oncology, Second Affiliated Hospital of Dalian Medical University, Dalian, China; 12Integrative Chinese and 194P Western Drugs, Dalian Medical University, Dalian, China The clinicopathological characteristics and proteomics Background: The greater the damage caused by ischemic and analysis of highly aggressive T1N2M0 NSCLC patients neurological deficiencies, the higher the likelihood of heart complications. Besides, the heart’s impaired function indicates that the related X. Lei Tianjin Medical University General Hospital, Tianjin, China ischemic lesion may lead to poor functional performance and secondary Background: Metastasis is the prominent cause of cancer-related complications. Various mechanisms suggested the interaction between deaths, yet this complex process remains the least known aspect of heart and brain. cancer biology. Lymph node metastasis is the most common and Methods: In the present work, we designed a registry-based study of important way of cancer cell dissemination; however the underlying data that were collected from the SEER public database based on the ’ – mechanisms are still not fully elucidated. 2018 submission. All cancer sites with a year s interval (2010 2016) ’ Methods: From 2018 January 1 to 2019 December 31, 35 non-small cell and stage IV adult patients were extracted. The majority of associated lung cancer (NSCLC) patients with T1N2M0 underwent surgical brain metastasis and heart-specific death was seen in the lung cancer treatment in our hospital. The clinical and pathological characteristics site (81.4%). We extracted data on patients with stage IV lung and of these patients were reported. We also analyzed T1N2M0 NSCLC bronchus and divided them into two groups; the brain Mets (BM) group patients from thee SEER database. In addition, we collected primary lung and the non-brain Mets (non-BM) group.

Journal of Thoracic Oncology Vol. 16 No. 4S: S803–S804 S804 Journal of Thoracic Oncology Vol. 16 No. 4S

Results: We extracted 3187 patients with lung and main bronchus site significance of heart- fatal events was confirmed after adjusting for from SEER including 417 patients who experienced fatal heart-specific multiple variables with the Cox regression multivariate analysis (HR = with a history of brain Mets which considered as brain Mets group. The 0.76, CI = 0.68–84, P =< 0.0001). second group of heart-specific death included 2770 patients who were Conclusions: In conclusion, patients with lung cancer revealed the most stated as the non-brain Mets group. All patients had received cancer common heart-related death with brain metastatic site among all cancer treatments for advanced disease (stage IV). Patients who had sites. In the lung, the brain metastatic site associated with poorest experienced heart-specific death in the brain Mets group was survival of heart-specific death patients compared with the non-brain predominantly male, right side, upper site, and non-small type metastatic group. We may be at the gates of a new field of scientific (62.11%, 54.92%, 51.56%, 69.78%) respectively. There was a statistical research on neurocardiooncology. difference in the survival outcomes between the heart death patients Legal entity responsible for the study: The authors. with brain Mets cohort and the non-brain Mets (P = 0.003; median Funding: Has not received any funding. survival: 2 months vs. 3 months). The negative prognostic independent Disclosure: All authors have declared no conflicts of interest. ABSTRACTS

Disclosure: C.M. Della Corte: Advisory/Consultancy: MSD. F. Ciardiello: MESOTHELIOMA Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/ Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Pfizer; 196P Advisory/Consultancy: Sanofi; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Servier; Advisory/Consultancy: BMS; A pivotal multicenter translational research project on Advisory/Consultancy: Celgene; Advisory/Consultancy: Lilly; Advisory/ malignant pleural mesothelioma (MPM): Preliminary results Consultancy, Research grant/Funding (institution): Amgen; Research grant/ Funding (institution): AstraZeneca; Research grant/Funding (institution): Ipsen. ı́ R. Di Liello1, C.M. Della Corte1, V. Ciaramella1, A. Insa2, P. Mart n-Martorell: Speaker Bureau/Expert testimony, Travel/Accommodation/ ̃ 2 2 ́2 3 1 Expenses: BMS; Speaker Bureau/Expert testimony, Travel/Accommodation/ D. Compan-Quilis , G. Alonso , R. Borras , G. Viscardi , N. Zanaletti , Expenses: Roche; Travel/Accommodation/Expenses: MSD; Advisory/ 1 4 4 5 F. Sparano , I. Cozzolino , M. Montella , G. Vicidomini , Consultancy, Speaker Bureau/Expert testimony: AstraZeneca. F. Morgillo: I. Pastor-Escartıń2, M. Santini5, R. Franco4, F. Ciardiello1, Advisory/Consultancy: MSD; Advisory/Consultancy: Lilly; Research grant/ P. Martın-Martorelĺ 2, F. Morgillo1 1Medical Oncology, Precision Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest. Medicine Department, Universitàdegli Studi della Campania Luigi Vanvitelli, Naples, Italy; 2Medical Oncology Department, Hospital Clınicó Universitario de Valencia, Valencia, Spain; 3Medical Oncology, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy; 4Division of 197P Pathology, Department of Mental and Physical Health and Preventive Development of a core outcome set for clinical studies of the Medicine, Universitàdegli Studi della Campania Luigi Vanvitelli, Naples, invasive management of malignant pleural mesothelioma: Italy; 5Thoracic Surgery Unit, Universitàdegli Studi della Campania Luigi The COSi-meso initiative Vanvitelli, Naples, Italy K. Chandarana, A. Gkikas, E. Caruana, A. Nakas Thoracic Surgery, Background: Platinum-based therapy (PL) remains the standard of care Glenfield Hospital - University Hospitals of Leicester NHS Trust, Leicester, in MPM, despite encouraging emerging data from immunotherapy (IO) UK trials. Recently, prognostic MPM clusters with potential implications for targeted-treatments were identified by multiplatform profiling but we Background: Heterogeneity in outcome measurement and reporting are still far from translating these data in therapeutic opportunities for renders meaningful literature synthesis challenging, and contributes to pts. In this scenario, we are leading an international multicenter project research waste. We sought to systematically evaluate the outcomes on new biomarkers in MPM. reported to date in studies of invasive management of malignant pleural Methods: We used preclinical models to compare PL-naïve and PL- mesothelioma (MPM). resistant MPM. Protein expression of biomarkers of interest from cells Methods: Eligible studies and protocols (2010 to 2020) were identified were analyzed by FACS and Western blot at Universitàdegli Studi della from electronic databases (Medline, Embase, Cochrane) and clinical trial Campania Luigi Vanvitelli (Naples, IT). Further, specimens of MPM pts registries (ClinicalTrials.gov, clinicaltrialsregister.eu, isrctn.com). Data treated with PL and IO will be used for an IHC-based pivotal analysis on was extracted for all clinical primary and secondary outcomes, and known and emerging biomarkers as BAP1, AURKA and CDKN2A. VISTA associated measures. COS iMeso was registered with COMET (Core and PD-L1 will be also analyzed and correlated to other results. Outcome Measures for Effectiveness Trials) in November 2019 (http:// Results: In PL-resistant MPM H2452 cells, generated treating parental www.comet-initiative.org/studies/details/1426) and is funded by a cell line with PL dose-escalation, FACS analysis revealed an increased BASO∼ACS (NIHR) Project Grant. PD-L1 expression (1% in PL-naïve vs. 39.1% in PL-resistant). Western Results: Literature searching returned 2,636 abstracts, of which 88 blot protein expression analysis confirmed this result, suggesting a papers underwent full-text review, and 10 were included in final analysis. PL-driven increased IO-sensitivity, independent from response, as An additional 5 studies were included from clinical trial registries. The shown in other cancer types. Sixty-two MPM pts treated at Hospital most frequently-reported endpoints were: survival in 87% (13/15) of Clınicó Universitario de Valencia (Valencia, ES) from 2001 to 2020 were the studies, adverse events and perioperative morbidity in 73% (11/15), selected for the translational part of the project so far. Mean age was 67.5 quality of life (QoL) in 60% (9/15), disease progression in 53% (8/15), years (36–89), 90% (n = 56) of pts were male, 80% (n = 50) exposed to length of hospital stay in 20% (3/15) and health economic outcomes in asbestos and 61% (n = 38) ECOG PS <2. The majority (69%, n = 43) with 13% (2/15). There were significant discrepancies in the intervals for epithelioid MPM; 52% (n = 33) stage III–IV at diagnosis. Of 58 pts which survival was reported, ranging from perioperative period to 5 included in the analysis, 4 were exposed to IO and 45 (77%) to PL. 62% years, with minimal overlap or consistency between studies. QoL was (n = 28) PL-sensitive and 38% (n = 17) PL-resistant. IHC analysis on assessed by 19 different tools, with the most frequently monitored time tissue specimens is ongoing. interval being at 3 and 6 months in 39% of studies reporting QoL Conclusions: Our preliminary results confirmed the activation of PD-L1 assessments. by PL, also in resistant setting, showing a biological rationale for IO in Conclusions: Outcome reporting in studies on the invasive management these pts. Ongoing analysis will validate on a proteomic level other for malignant pleural mesothelioma is highly variable. This review proposed biomarkers as BAP1, AURKA, CDKN2A and VISTA, to build a reinforces the need to define a “core outcome set” to inform future cost-effective IHC-based MPM classification, useful for future targeted- research and allow meaningful comparison and analysis across studies treatment strategies. in this field. Legal entity responsible for the study: The authors. Legal entity responsible for the study: The authors. Funding: Universitàdegli Studi della Campania Luigi Vanvitelli, Naples, Funding: BASO∼ACS (NIHR) Project Grant. Italy. Disclosure: All authors have declared no conflicts of interest.

Journal of Thoracic Oncology Vol. 16 No. 4S: S805–S807 S806 Journal of Thoracic Oncology Vol. 16 No. 4S

E. Felip: Advisory/Consultancy: Bristol-Myers Squibb Recipient; Advisory/ Consultancy: F. Hoffmann La Roche AG; Advisory/Consultancy: Merck Sharp & 198P Dohme; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Analysis of efficacy of immunotherapy according to histology MSD Oncology; Advisory/Consultancy: Novartis. All other authors have declared in malignant pleural mesothelioma (MPM) patients no conflicts of interest.

S. Cedres1, J.D. Assaf1, P. Iranzo1, A. Callejo1, N. Pardo1, A. Navaro1, A. Martinez-Marti1, H. Bote2, D. Marmolejo1, J. Lostes1, V. Monton1, 199P 1 1 3 1 J. Gonzalo , A. Pedrola , E. Felip Medical Oncology Department, Vall Clinical and epidemiological characteristics of patients with ’ d Hebron Institute of Oncology and University Hospital, Barcelona, Spain; pleural mesothelioma in the United States 2Hospital Universitario 12 de Octubre, Madrid, Spain; 3Medical Oncology ’ Service (Lung Cancer Unit), Vall d Hebron University Hospital, Barcelona, D.M. El-Habashy Department of Clinical Oncology, Menoufia University - Spain Faculty of Medicine, Shebeen El-Kom, Egypt

Background: MPM is a highly aggressive pleural tumor associated with Background: Malignant Pleural Mesothelioma (MPM) is considered a asbestos exposure and with limited survival despite systemic therapy. In rare, highly aggressive malignancy affecting the pleura, with majority of previously treated patients (p), no-randomized studies of immunother- cases are associated with asbestos exposure. According to the 2015 apy (ICI) have demonstrated activity, and Checkmate 743 demonstrated World Health Organization (WHO) classification, MPM is, histologically, survival benefit of ICI in first line with some differences according to subdivided into three types; Epithelial MM, Sarcomatoid MM and histology. The objective of this study is to characterize the impact of ICI Biphasic MM. In this study, we analyze the clinic-epidemiological and use on survival in p diagnosed with MPM at our institution. pathological characteristics of patients diagnosed with MPM at the ’ Methods: We review 189 MPM p diagnosed at Vall d Hebron University united states from 2000 till 2015. Hospital between November 2002 and April 2020. Associations between Methods: This, cross sectional study, was conducted using SEER Stat* clinical variables and outcome were assessed with Cox regression version 8.3.8. Clinical data were obtained from SEER Research Data 9 models and survival data were calculated by the Kaplan-Meier method. Registries Nov 2019, then the extracted data were, statistically, analyzed ’ – Results: Patient s characteristics: median age 68 years (y) (45 88 y), using SPSS version 22. males: 70%, performance status (PS)1: 69%, asbestos exposure: 74%, Results: From 2000 to 2015, 167 patients were diagnosed as MPM, with epithelioid subtype: 76%. First line chemotherapy was offered to 85% of male predominance (n = 105, 62.9%). The mean age of the diagnosed p (66% cisplatin-pemetrexed and 27% carboplatin-pemetrexed) and 19 patients was 68.02, ranging from 10 to 85 years. The incidence of MPM p were treated in clinical trials in first line. Median progression free was estimated to be about 0.37 per 1.000.000, and the majority of cases – survival (PFS) was 4.4 months (m;CI95% 3.1 5.4). Median survival (OS) have their tumor occupying the right sided pleura (n = 88, 52.7%). – in overall population was 21.3 m (95%CI17.2 24.3). Epithelioid Malignant epithelial neoplasm was the commonest histology among the histology, PS 0, neutrophil-lymphocyte ratio >5 and treatment with diagnosed cases (n = 52, 31.1%), followed by malignant fibrous cisplatin vs. carboplatin were associated with significant improvements neoplasm (n = 46, 27.5%). Surgery was performed in more than 40% in OS. In second line 27 p were treated with ICI in clinical trials. Median of cases (n = 70, 41.9%), while, in more than one third of cases, surgical – OS for p treated with ICI was 22.6 m (95%CI 11.1 34). No differences in intervention was not recommended (n = 64, 38.35). The tumor was the PFS and OS for p treated with ICI were detected according to histology. only primary malignancy diagnosed in about three fourths of cases (n = Median PFS 2.7 m in epithelioid and 3 m in no-epithelioid (HR0.7, p = 122, 73%). The median survival was about 8 months with the relative – 0.43 CI95% 0.3 1.7) and OS 28.3 m in epithelioid and 13.8 m in no- and observed 5-year survival were 24.5% & 21.9%, respectively. – epithelioid (HR3.4 p = 0.01 CI95% 1.3 8.7). When we considered the OS Conclusions: MPM is a rare, highly lethal malignant neoplasm, with of p treated with ICI from the time of initiation of the ICI, the median OS male predominance. Malignant Epithelial Mesothelioma constitutes the for epithelioid p was 12.4 m vs. 6.18 m for no epithelioid (HR2.1, p = commonest histological subtype. Right sided pleura was more common – 0.09 CI95% 0.8 5.2). to be affected, with surgery was offered for most of cases. The median OS Conclusions: In our series, ICI was an acceptable option for previously was quite dismal with estimated observed 5-year survival was about treated MPM patients. We confirmed histology is a prognostic factor with 21%. better OS for p with epithelioid tumors. However, we could did not Legal entity responsible for the study: The author. demonstrate histology is a predictive factor for efficacy of ICI. Funding: Has not received any funding. Legal entity responsible for the study: The authors. Disclosure: The author has declared no conflicts of interest. Funding: Has not received any funding. Disclosure: S. Cedres: Advisory/Consultancy: Bristol-Myers Squibb Recipient; Advisory/Consultancy: F. Hoffmann La Roche AG; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: MSD 200P Oncology; Advisory/Consultancy: Amphera. P. Iranzo: Advisory/Consultancy: Prognostic factors in malignant pleural mesothelioma: A Bristol-Myers Squibb Recipient; Advisory/Consultancy: F. Hoffmann La Roche AG; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: multicentric study Boehringer Ingelheim; Advisory/Consultancy: MSD Oncology; Advisory/ Consultancy: Rovi; Advisory/Consultancy: Kyowa Kirin. A. Callejo: Advisory/ M.M. Baptista1, J. Barata1, G. Fernandes2, S. Saleiro3, Consultancy: Bristol-Myers Squibb Recipient; Advisory/Consultancy: F. Hoffmann 4 ̃ 2 1 1 La Roche AG; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Boehringer M. Souto Moura , A. Magalhaes , M.J. Valente , M.L.S.B. Valente 1 Ingelheim; Advisory/Consultancy: MSD Oncology; Speaker Bureau/Expert testi- Pulmonology Dept., Centro Hospitalar Cova da Beira, Covilha, Portugal; mony: Kyowa Kirin. N. Pardo: Advisory/Consultancy: Bristol-Myers Squibb 2Pulmonology Dept., Centro Hospitalar São João, Porto, Portugal; Recipient; Advisory/Consultancy: F. Hoffmann La Roche AG; Advisory/ 3Pulmonology Dept., Instituto Português de Oncologia Porto, Porto, Consultancy: Pfizer; Advisory/Consultancy: Boehringer Ingelheim. A. Navaro: 4 Speaker Bureau/Expert testimony: Bristol-Myers Squibb Recipient; Advisory/ Portugal; Pathology Dept., Instituto Português de Oncologia Porto, Porto, Consultancy: F. Hoffmann La Roche AG; Speaker Bureau/Expert testimony: Pfizer; Portugal Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Oryzon Genomics. A. Martinez-Marti: Advisory/Consultancy: Bristol-Myers Squibb Background: Malignant pleural mesothelioma (MPM) is a rare entity Recipient; Advisory/Consultancy: F. Hoffmann La Roche AG; Speaker Bureau/ with poor prognosis linked to previous exposure to asbestos. The main Expert testimony: Pfizer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/ study goal was to analyse the impact of clinical factors present at Consultancy: MSD Oncology; Advisory/Consultancy: Merck Sharp & Dohme. diagnosis on MPM prognosis. April 2021 Abstracts S807

Methods: Retrospective study of patients with MPM diagnosed between with disease progression within 6 months (p ≤0 .001). Chemotherapy 1999 and 2019 in three Portuguese hospitals. Descriptive and survival (p ≤0 .001) and epithelioid histological subtype (p = 0.01) were analysis were performed with software IBM SPSS v25. protective. Results: 60 patients were included, with male predominance (70%) and Conclusions: We failed to obtain sufficient rates of histopathological mean age of 67 ± 11 years old. At diagnosis, 60.8% had TNM stage III–IV, confirmation compared with the expected rate of ≥95% recommended 53.1% had significant weight loss and 17.9% had a Performance Status by NMA. All patients with adequate PS 0–1 should be offered active anti- (PS) ECOG ≥2. Asbestos exposure was mentioned in 48.3%, but this may cancer treatment and 60% or above of patients with PS 0–1 need to be be underestimated. Diagnosis was made mainly through pleural biopsy referred for chemotherapy, which we just achieved. No data from other (52.5%) and medical thoracoscopy (20.3%). Epithelioid mesothelioma regional hospitals are available. The Northern Cancer Alliance has was the main histological type (68.3%). 88.7% received first line agreed to the setting up of a regional mesothelioma MDT. Expressions of chemotherapy, mainly with platinum and pemetrexed doublet. 15 interests have been sent out to every hospital in the region and a referral patients had radiotherapy. Surgical approach included Pleurectomy/ form has been developed. Inital meetings have taken place with the 2 Decortication in 4 cases and Extrapleural Pneumonectomy in 2. One clinical leads and 2 mesothelioma nurses to agree on a timings of the patient received Nivolumab after progression. Median overall survival meeting, information technology support as well as the governance (OS) was 13 months, with median progression free survival of 10 months. framework behind it. We hope to improve staging, diagnosis, classifica- We performed a Kaplan-Meier analysis to evaluate possible prognostic tion by subtype and treatment by concentrating expertise. factors. OS was shorter in patients with PS ECOG ≥2 (20 versus 2 months, Legal entity responsible for the study: The author. p < 0.001) and ≥70 years old (20 vs. 10 months, p = 0.020). Cases with Funding: Has not received any funding. TNM stage III-IV also presented lower OS (20 vs. 11 months, p = 0.029). Disclosure: The author has declared no conflicts of interest. We applied the clinical prediction model for MPM prognosis proposed by Brims et al. and confirmed that OS was significantly different between the risk groups (p = 0.002). Patients in risk group 4 showed almost 4 times 202P – more risk to die than those in group 2 (HR 3.66, CI [1.58 8.46], p = 0.002). Indwelling pleural catheter removals in a large volume centre In a multivariate analysis with Cox regression model, Brims risk group 4, in the North East of England age ≥70 years old and TNM stage III-IV showed an independent prognostic value for patients with MPM (p < 0.001). A. Aujayeb Respiratory Medicine, Northumbria HealthCare NHS Conclusions: Identification of prognostic factors at diagnosis, like age Foundation Trust, Newcastle, UK and TNM stage, and use of specific prognostic models, such as Brims model, may represent valuable tools to guide MPM management. Background: Indwelling pleural catheters (IPCs) help in pleural Legal entity responsible for the study: The authors. effusion management and are removed. Locally, all removals are done Funding: Has not received any funding. in theatre, with pre-operative antibiotics. Talc is not instilled and Disclosure: All authors have declared no conflicts of interest. aggressive drainage is not pursued. Methods: With Caldicott approval, a retrospective review of IPCs removed between Jan 2015 and Oct 2020 was conducted. Basic 201P demographics, clinical details and outcomes were collected. Inequality in mesothelioma care in the North East of England Descriptive statistical methodology was applied. Results: Total number of IPCs performed was 229. IPCs removed A. Aujayeb Respiratory Medicine, Northumbria HealthCare NHS numbered 63, (27.5%). 37 (58.7%) were male. Performance status was Foundation Trust, Newcastle, UK 0 (22), 1 (25), 2 (10) and 3 (6). Diagnoses were benign fibrinous pleuritis (5), liver failure (1), heart failure (1), mesothelioma (18), lung Background: In the UK, the national lung cancer audit runs the National cancer (14), breast cancer (11), other cancers (9) and unexplained Mesothelioma Audit (NMA) every 3 years. In 2020, the NMA showed effusions (4). Median time to removal was 183 days (IQR: 98–265; range: Northumbria to have low rates of histopathological confirmation, 27 to 434). Pleural fluid cytology was not sent in 1, inconclusive in 8, treatment and one-year survival rates for malignant pleural mesotheli- suspicious in 1, negative in 28 (mean time to removal 187 days) and oma (MPM). We hypothesized that an internal analysis over a 10-year positive in 25 (mean 193) [p = 0.66]. Non-expandable lung was present period provides valuable insights into presentation, diagnosis, treatment in 58 (92%). 37 had chemotherapy, 3 after IPC removal only. There was and outcomes. We also surmised that the evidence would help reduce no difference in time to removal between those groups. [34 (mean 183 inequality in care. days) vs. 26 (195), p = 0.26]. There was no infection before removal. Methods: A single-centre retrospective case series of all confirmed Mean days to removal with loculations was 151 (n = 17) vs. 195 (n = 46) mesothelioma from 1 January 2009 to 31 December 2019 was with no loculations [p ≤0 .05]. 2 IPCs fractured (distal end of 1 was cut performed. Demographics, clinical, radiological and histopathological as it could not be removed). 1 patient developed post removal cellulitis. characteristics and outcomes were collected. None needed further interventions. Results: 247 patients had pleural mesothelioma. 86% were male with a Conclusions: Removal is more likely in the absence of lung entrapment, mean age of 75.7 years. Dyspnoea (77.4%) and chest pain (38.5%) were in patients with good (PS) and loculations. Treatment with chemother- the commonest symptoms. 64.9 and 71.4% had pleural thickening and apy with an IPC in situ and positive cytology are not associated with effusion respectively. 86.8% had at least one attempt to obtain a tissue reduced time to IPC removal. Failure to remove is less than 5%. biopsy, but histopathological confirmation was acheived only in 108 Legal entity responsible for the study: The author. (43.7%). 66.3% with PS 0 and 1 (62.7% of total cohort) had at least one Funding: Has not received any funding. anti-cancer therapy. Death within 12 months was associated Disclosure: The author has declared no conflicts of interest. ABSTRACTS

Conclusions: This nationwide cohort shows that clinicians in the UK GENERAL INTEREST changed the management of patients with stage 1–3 lung cancer in line with national guidelines. The main changes are a reduction in 203MO chemotherapy use and an increase in RT hypofractionation. Changes in management for patients with lung cancer treated Legal entity responsible for the study: University of Manchester. Funding: Biomedical Research Centre, Manchester. with radical radiotherapy during the first wave of the Disclosure: K. Thippu Jayaprakash: Travel/Accommodation/Expenses: COVID-19 pandemic in the UK (COVID-RT Lung) Bayer UK; Travel/Accommodation/Expenses: Janssen Oncology; Travel/ Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Roche; K. Banfill1, G. Price2, K. Wicks2, A. Britten3, C. Carson4, M. Hatton5, Travel/Accommodation/Expenses: Takeda; Research grant/Funding (self): UK National Institute of Health Research Clinical Research Network Eastern. K. Thippu Jayaprakash6, A. Jegannathen7, C.L. Lee8, N. Panakis9, 10 11 12 13 14 C. Peedell: Speaker Bureau/Expert testimony: Elekta; Speaker Bureau/Expert C. Peedell , C. Stilwell ,T.Pope , C. Powell , V. Wood , testimony: Boston Scientific; Speaker Bureau/Expert testimony: AstraZeneca. S. Zhou15, C. Faivre-Finn1 1The Christie NHS Foundation Trust, C. Faivre-Finn: Research grant/Funding (institution): Elekta. All other authors have Manchester, UK; 2Manchester Cancer Research Centre, Manchester, UK; declared no conflicts of interest. 3Royal Sussex County Hospital - Brighton and Sussex University Hospitals NHS Trust, Brighton, UK; 4Northern Ireland Cancer Centre, Belfast, UK; 5Weston Park Hospital, Sheffield, UK; 6Oncology, Addenbrooke’s Hospital - 204P Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Immune-related adverse events (IrAEs) as a predictor of 7 8 University Hospitals of North Midlands, Stoke-on-Trent, UK; New Cross response to immunotherapy in patients with lung cancer Hospital, Wolverhampton, UK; 9Oxford University Hospitals, Oxford, UK; 10 11 South Tees NHS Foundation Trust, Middlesbrough, UK; Aberdeen Royal M.V. Sanchez Becerra1, R. Martinez-Cabañes1, A. Gonzalez-Lopez1, 12 Infirmary, Aberdeen, UK; The Clatterbridge Cancer Centre NHS E. Zhan-Zhou2, V. Sotelo1, M. Esteban1, T. Robles1, J.C. Camara1, 13 Foundation Trust, Liverpool, UK; Velindre Cancer Centre, Cardiff, UK; A. Cardeña1, S. Hernando1, A. Hurtado2, D. Moreno1, C. Olier1, 14 University Hospital Southampton NHS Foundation Trust, Southampton, X. Mielgo Rubio1 1Medical Oncology, Hospital Universitario Fundacioń 15 UK; Beatson West of Scotland Cancer Centre, Glasgow, UK Alcorcon,́ Alcorcon, Spain; 2Hospital Universitario Fundacioń Alcorcon,́ Background: In response to the COVID-19 pandemic, guidelines on Alcorcon, Spain reduced fractionation for patients with lung cancer treated with Background: Immune Checkpoint Inhibitors (ICI) are a standard of care curative-intent radiotherapy (RT) were published (Faivre-Finn et al) in advanced Non-Small Cell Lung Cancer. Some patients seem to have aiming to reduce the number of hospital attendances and potential maintained responses even when treatment is withdrawn. There is a exposure of vulnerable patients to SARS-CoV-2. Here we describe the critical need to distinguish this group of patients by identifying changes that have taken place. predictors of response to ICI. PD-L1 expression, tumor burden and Methods: COVID-RT Lung is a prospective multicentre UK data microsatellite instability have been validated. However, new biomarkers – collection. Inclusion criteria are: patients with stage 1 3 lung cancer (tumor infiltrating lymphocytes, tumor neoantigen burden, neutrophil/ (biopsy-proven or diagnosed on cross-sectional imaging) referred for lymphocyte ratio, etc.), are on study. We aim to investigate the – and/or treated with radical RT between 2/4/2020 2/10/2020. Both relationship between IrAE and response to ICI. patients who had a change in their management and those who continue Methods: Retrospective study with patients receiving ICI from January with standard management are included. Data on demographics, COVID- 2013 until May 2020 in our Centre. Kaplan-Meier and Log Rank test were 19 diagnosis, diagnostic work-up, RT and systemic treatment, treatment- calculated. related toxicity, disease/patient status are collected. Each participating centre obtains local approval and anonymised data is collected on a Table 204P: Immune-related adverse events (IrAEs) as a predictor of central, cloud-based Research Electronic Data Capture system. response to immunotherapy in patients with lung cancer Results: 1117 records from 20 UK RT sites were available for analysis on Male 77.6% – 30/11/2020. 562 (50%) female, median age 72 years (38 93 years). 15 Female 22.4% patients (1%) were diagnosed with COVID-19, 9 prior to treatment. 160 Adenocarcinoma 51.3% patients (14%) had their diagnostic investigations affected by the NOS 7.9% pandemic. 415 patients (37%) had their treatment changed from their Squamous 39.5% centre’s standard of care (table). Patients with PS0-1 were more likely to Small Cell 1.3% have their treatment changed compared to patients with a poorer PS. PD-L1 The median number of RT fractions was 15 for patients who had their RT >49% 24.4% dose/fractionation changed compared to 20 for those who were treated 1-49% 46.7% <1% 28.9% as per standard of care. Toxicities - Skin 36.8% - Arthritis 21% Table 203MO: Changes to management of patients treated for stage - Diarrhea 18.2% 1–3 lung cancer during the COVID-19 pandemic - Hepatitis 10.5% - Thyroid 9.2% Change in management Patients - Pneumonitis 9.2% - Pancreatitis 2.6% Different RT dose/fractionation 210 - Gastritis 2.6% RT instead of surgery 86 - Adrenal 2.6% Chemotherapy omitted 87 - Nephritis 1.3% Chemotherapy reduced 56 - Neuritis 1.3% Watch and wait 24 No treatment 3 Immunotherapy omitted/reduced 6 Results: 76 patients were included. Patient characteristics and toxicities PCI omitted 4 are summarized in the table. 55.3% patients presented toxicity: 30.9%, 45.2% and 23.8% grade I, II and III respectively (attending CTCAE v5.0). 13 patients suspended ICI, 11 required corticosteroids, and 7 were

Journal of Thoracic Oncology Vol. 16 No. 4S: S808–S814 April 2021 Abstracts S809 hospitalized. The 24-month overall survival (24 mo-OS) was 18.6% – (CI95 6.4 35.7%) in patients without toxicity and 66.4% (CI95 47.2- 206P – 80%) in those with toxicity (HR 0.3, p < 0.001; CI95 0.16 0.59). Impact of the COVID-19 pandemic in the diagnosis of lung – Considering intensity of IrAEs, 24 mo-OS rates were 18.6% (CI95 6.4 cancer in Portugal – – 35.7%), 67.8% (CI95 45.2 82.7%) and 70% (CI95 32.9 89.2%) for no toxicitiy, grade I/II and grade III/IV respectively. 24-month progression M. Leitão1, A.R. Teixeira2, M.C. Neves2, I. Azevedo2, C. Vieira2 – 1 free survival (24 mo-PFS) was 8.6% (CI95 0.8 28.4%) in patients Medical Oncology Department, Instituto Portugues de Oncologia, Porto, – 2 without IrAEs and 39.1% (CI95 22.4 55.5%) with IrAEs (HR 0.4, p 0.003; Portugal; IPO Porto, Porto, Portugal − CI95 0.22 0.74). According to IrAE intensity, 24 mo-PFS was 8.6% (CI95 – – – Background: In 2020 the world was confronted with a pandemic that 64.3 95.6%), 41.5% (CI95 22.9 59.2%) and 48.2% (CI95 12.8 77.2%) for no toxicitiy, grade I/II and grade III/IV respectively. imposed unforeseen burden on health care systems. A severe impact was Conclusions: IrAEs could be a predictive biomarker, especially in severe predicted on the diagnosis and treatment of cancer. However, real-world grades of toxicity. However, prospective studies are needed. objective data is lacking. Legal entity responsible for the study: Sanchez-Becerra, Maria Methods: We analysed medical records relative to the first Medical Virginia. Oncology - Lung consultations in a specialized oncological center, Funding: Has not received any funding. comparing Sept/Oct 2019 to Sept/Oct 2020 (coincidental with the Disclosure: All authors have declared no conflicts of interest. beginning of the second COVID-19 surge in Portugal). Descriptive and statistical analysis were performed using SPSS software. Results: In our sample (n = 174, 94 diagnosed in 2019, 80 in 2020), 78% were male, with a median age of 64 years old in 2019 and 69 in 205P 2020. The most common histological type was adenocarcinoma. In 2019 Impact of UK COVID-19 pandemic cancer guidelines on 81% of cancers were classified as advanced compared to 79% in 2020; treatment decisions for thoracic malignancies 65% as stage IV vs.61% and in both groups 28% were candidates for curative therapy. The diagnosis was made from incidental findings in J. Morton-Gittens, N. Pipalia, K. Thippu Jayaprakash Oncology, 23% vs.19% in 2020; 76% vs.78% were symptomatic. The median time The Queen Elizabeth Hospital King’s Lynn NHS Foundation Trust, King’s from symptom onset was 3 vs.2 months. In 2019 30% initiated palliative Lynn, UK chemotherapy vs. 35%, 15% vs.16% had surgery, 15% vs.13% were Background: Covid-19 pandemic is having significant impact on cancer offered best supportive care and 11% vs.6% therapy with TKI. At the services globally. Several UK national guidelines have been developed to time of data collection, 35,1% of all patients had died. There was no adapt cancer services to mitigate the risks from Covid-191. We wished to statistical significant difference between 2019 and 2020 data, namely in study the impact of these guidelines on treatment decision making for stage distribution, curative/palliative intent treatment, incidental thoracic malignancies. diagnosis vs. from symptoms, time from onset of symptoms to first Methods: Between April and September 2020, we prospectively Medical Oncology consultation, ECOG status, symptom control or need collected information on treatment decisions made for newly diagnosed for hospitalization, nor in the proportion of patients fit for treatment vs. lung cancer and mesothelioma patients within a UK ‘hub and spoke’ best supportive care. No statistical significant difference in the likelihood cancer care delivery model, and analysed the impact of these guidelines of death in the first 2 months was found. on treatment decision making. Conclusions: We need scientific evidence, instead of mere speculation, Results: n = 65 (male - 41; female - 24). Median age: 72 years (41–93). in order to appropriately face the challenges ahead. In our study, there Staging and histology distribution: Stage I - 7 (non-small cell lung cancer were no findings of significant impact of COVID-19 pandemic on [NSCLC] - 6; unknown - 1), Stage II - 7 (NSCLC - 6, small cell lung cancer diagnosis of lung cancer during the period of time analysed. We infer [SCLC] - 1), Stage III - 16 (NSCLC - 13, SCLC - 3), Stage IV - 33 (NSCLC - that this may be due to the higher alertness to respiratory symptoms due 27; SCLC - 5; no histology - 1) and mesothelioma - 2. The treatment to fear of SARS-CoV-2 infection, in addition to the remarkable effort intent was radical or adjuvant for 23 patients (35.4%) and palliative for carried out by primary care providers despite the difficulties. More data 42 (64.6%). 26 (40.0%) were considered for systemic anti-cancer is needed. treatments (SACT) with differing treatment priority levels1 (level two - Legal entity responsible for the study: The authors. 5; three- 1; four - 4; five - 2; six - 14) and 36 (55.4%) were offered Funding: Has not received any funding. radiotherapy (priority level one - 16; three - 3; four - 15; five - 2). Two in Disclosure: All authors have declared no conflicts of interest. radical and two in palliative intent treatment groups had minor modifications to SACT with the addition of an antibiotic and G-CSF while one treated with palliative intent had a positive impact of offering 207P first line Osimertinib. Both mesothelioma patients were treated with Lung immune prognostic index and survival in patients with palliative intent with no modification to the standard of care. non-small cell lung cancer: A systematic review Conclusions: In our cohort, only minor treatment modifications were made to a small number of patients with thoracic malignancies. This R.S. Heriyanto1, C. Chrystelle1, A. Hadisurya1, F. Tandy1, could partly be explained by the low prevalence of Covid-19 infection M. Suciningtias1, A. Kurniawan2 1Faculty of Medicine, Pelita Harapan seen in our region and reflecting patient and/or clinician preferences. University, Tangerang, Indonesia; 2Department of Internal Medicine, Ongoing larger scale Covid-19 prospective cohort studies would provide Pelita Harapan University, Tangerang, Indonesia further insights into the impact of Covid-19 pandemic on treatment decisions, survival outcomes and resource implications. 1The Response Background: Lung immune prognostic index (LIPI) is a biomarker that of the UK Clinical Oncology Community to the COVID-19 Pandemic has been recently developed based on the combination of derived Lewis, P.J. et al. Clinical Oncology, Volume 32, Issue 8, 493–496. neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) Legal entity responsible for the study: The authors. and is used as a prognostic factor of immune checkpoint inhibitor (ICI) Funding: Has not received any funding. therapy in non-small cell lung cancer (NSCLC). There is much research Disclosure: K. Thippu Jayaprakash: Research grant/Funding (self): UK National that discusses LIPI in correlation with the prognosis of NSCLC patients Institute of Health Research Clinical Research Network Eastern; Travel/ treated with ICI. However, its effectiveness and utilization beyond ICI are Accommodation/Expenses: Bayer UK, Janssen Oncology, Pfizer, Roche and unclear. This systematic review aims to evaluate the effectiveness of LIPI Takeda. All other authors have declared no conflicts of interest. and its usage outside of ICI. S810 Journal of Thoracic Oncology Vol. 16 No. 4S

Methods: We performed a systematic search of PubMed, PMC, Science Table 208P Direct, Google Scholar, and Europe PMC, on January 2nd 2021, using a No AID (n = 32) AID (n = 8) p-value combination of keywords associated with LIPI, its prognostic value in lung cancer patients and their variations or synonyms. Publications PD-L1 TPS 0.53 included are limited to English manuscripts with cohort and clinical 0% 1 1 trials design only, that were published in the past 10 years; we excluded <1% 4 1 1–50% 11 4 NSCLC patients treated with ICI monotherapy. The prognostic value was >50% 15 2 measured by the median overall survival (OS). All studies were reviewed Unknown 1 0 by all six authors. The quality of each included study was assessed using Median cycles 6 3.5 the Newcastle-Ottawa Scale (NOS) and Jadad score. Total number of irAEs 0.25 Results: We included a total of four retrospective cohort and one 0126 randomized clinical trial studies consisting of 3880 patients. Based on 1132 NOS, all cohort studies were good quality, while the randomized clinical 260 trial has a Jadad score of 4 out of 5. The association of LIPI and OS were 310 – found in all included studies. Four studies showed that good LIPI is Grade 3 5 irAEs >0.99 Grade 3 or 4 7 1 significantly associated with longer median OS, while intermediate and Grade 5 1 0 poor LIPI is significantly associated with worse median OS in lung cancer Best Response 0.39 patients treated not only with ICI but other treatment such as EGFR-TKI Stable disease 1 1 and chemotherapy. Two studies concluded that LIPI is not significantly Mixed response 4 0 associated with OS. Complete or Partial response 19 5 Conclusions: LIPI is proven to be associated with a median survival of Progressive disease 8 1 other lung cancer patients treated with other treatments than ICI, proving that LIPI is not specifically predictive for ICI and thus, making it Conclusions: When treated with ICIs, patients with well-controlled AID a promising tool for determining the prognosis of lung cancer patients. do not appear to have a worse irAE profile or worse outcomes than those Further prospective investigations are needed. without AID. The results of this study are hypothesis generating and Legal entity responsible for the study: Rivaldo Steven Heriyanto. should be further evaluated in larger studies and, furthermore, they can Funding: Has not received any funding. help inform clinical trial design. Disclosure: All authors have declared no conflicts of interest. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest. 208P Safety and efficacy of immune checkpoint inhibitors in NSCLC patients with autoimmune disease: A UK tertiary cancer 209P_PR centre experience Understanding patient experience in Europe: The first global lung cancer coalition patient experience survey P. Sawhney, G. Patel, D. Ohana, M.K. Luong, Y.N.S. Wong, A.J.X. Lee, S-M. Lee, M.D. Forster Cancer Division, University College London V. Beattie1, W. Boerckel2, M. Rigney3,K.O’Hagan4, M. Hennink5, Hospitals NHS Trust, London, UK J. Fox6 1Lung Cancer Nursing UK, Solihull, UK; 2Cancer Care, New York, NY, USA; 3GO2Foundation, Washington, DC, USA; 4Irish Cancer Society, Background: Immune checkpoint inhibitors (ICIs) have now become Dublin, Ireland; 5Longkanker Nederland, Utrecht, Netherlands; 6Roy the standard of care for non-small cell lung cancer (NSCLC), either alone Castle Lung Cancer Foundation, Liverpool, UK or in combination with chemotherapy, and are associated with immune related adverse events (irAEs). It is often assumed that patients with pre- Background: Little comparative European or global data exists on lung existing autoimmune disease (AID) are at increased risk of AID flare or cancer patient experience. The Global Lung Cancer Coalition (GLCC), a irAEs when exposed to ICIs, although there is a dearth of data to support partnership of 40 patient organisations across 29 nations, wanted to or refute this. We present experience of using ICIs in NSCLC at a large UK understand the experiences of lung cancer patients, identifying common tertiary cancer centre, comparing the efficacy and safety profile in those themes and differences between countries. The GLCC therefore used its with AID to those without. member networks to run a multi-national online survey of patients – the Methods: A single centre retrospective analysis of the electronic records first time this had been attempted. of NSCLC patients who were initiated on treatment with an ICI from Methods: The GLCC convened a steering group with members from the January 2017 to December 2020 was performed. There were 159 UK, Ireland, and the Netherlands, including patients, clinicians and patients who received ICIs, 8 of whom had pre-existing AID. These were advocates. 10 questions were agreed and translated into multiple cohort matched for tumour type, ICI agent, sex and age to patients languages with appropriate terminology. As well as demographic without AID, at a 1:4 ratio. questions, participants were asked what treatments they had received, Results: Table shows patient characteristics, irAEs and outcomes. The 8 whether they felt involved in decisions and were treated with dignity and patients in the AID cohort had: psoriasis (n = 2), sarcoidosis (n = 1), respect, and how they describe themselves. The survey was distributed rheumatoid arthritis (n = 1) lupus (n = 1), endocrinopathies (n = 3), IBD by GLCC members via emails, newsletters and social media. The results (n = 2) and PMR (n = 1). 3 patients had more than 1 AID. 3 were on no were collated and analysed by the steering group. The GLCC produced a treatment for their AID, 1 was on prednisone 3 mg and 4 were on global report with findings for all participating countries, as well as hormone replacement or topical agents. No significant differences were bespoke briefings comparing the perspectives of patients in each seen between cohorts for number or severity of irAEs or in response to country to those of global respondents, for national campaigning. treatment. 2 AID patients developed irAEs; 1 developed a G2 flare of pre- Results: Nine of the 17 countries that took part are in Europe: Bulgaria, existing psoriasis and 1 developed G3 hepatitis. 1 patient in the AID Czech Republic, Denmark, Ireland, Netherlands, Portugal, Spain, Sweden cohort has not yet had initial restaging imaging. and the UK. 574 of 907 patients who responded were from Europe (63%). Headline European findings include: 11% of respondents did not know what type of lung cancer they had (13% globally) 19% of respondents stated they did not feel involved in decisions about their treatment and April 2021 Abstracts S811 care (18% globally) 11% felt they had ‘never’ or only ‘sometimes’ been treated with dignity and respect by their treatment team (9% globally). 211P Conclusions: The survey demonstrates that a pan-European patient Prior antibiotic use in immunotherapy treated patients: The experience survey can take place. It also suggests more could be done experience of a community hospital across nations to improve lung cancer patients’ experience, particularly involvement in decisions around treatment and care. We are grateful to M. Vitorino, M.V. Batista, T. Tomás, S. Almeida, R. Freitas, M. Silva all the patients who responded and shared their experiences. Hospital Professor Doutor Fernando Fonseca EPE (Hospital Amadora/ Editorial acknowledgement: The abstract was written by Incisive Sintra), Lisbon, Portugal Health as policy and communications experts. All editorial control was retained by the authors. Background: Over the last few years, immunotherapy has become the Legal entity responsible for the study: The authors. standard of care for several cancer types. Multiple clinical studies tried Funding: The Global Lung Cancer Coalition (GLCC) receives funding for to find factors that can predict clinical response to immune checkpoint its work from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers inhibitors (ICI). Some of these studies demonstrated a negative impact of Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche and Takeda Oncology. previous treatment with broad-spectrum antibiotics (ATB). In this study, Disclosure: All authors have declared no conflicts of interest. we evaluate the prognosis of patients treated with ICI according to the previous use of ATB. Methods: Retrospective analysis of 114 patients treated with ICI 210P between 1 January 2016 and 30 June 2020. Past broad-spectrum Lung cancer: 10-year survival antibiotic use was defined as administration within 30 days before the start of ICI therapy. Overall survival (OS) and progression-free survival (PFS) curves were estimated using the Kaplan–Meier method. O. Kshivets Surgery, Roshal Hospital, Roshal, Russian Federation Results: From 114 patients treated with ICI, 84 (73.7%) were male, with Background: 10-Year survival (10YS) after radical surgery for non- a median age of 61 years. Regarding tumor sites: 80.7% non-small cell small cell lung cancer (LC) patients (LCP) (T1-4N0-2M0) was analyzed. lung cancer (NSCLC), 7.9% bladder, 5.3% renal, 2.6% colorectal, 0.9% Methods: We analyzed data of 768 LCP (age = 57.6 ± 8.3 years) breast, 0.9% thymus, 0.9% mesothelioma and 0.9% nasopharynx. radically operated (R0) in 1985–2021 (m = 660, f = 108; lobectomies = Nivolumab was used in 59 patients (51.8%), pembrolizumab in 50 514, pneumonectomies = 254, only surgery-S = 618, adjuvant chemo- (43.9%), durvalumab in 4 (3.5%) and atezolizumab in 1 (0.9%). Twenty- immunoradiotherapy-AT = 150: CAV/gemzar + cisplatin + thymalin/ four patients received ATB within 30 days previously to initiate ICI. taktivin + radiotherapy 45–50 Gy; T1 = 320, T2 = 255, T3 = 133, T4 = Seven (29.2%) patients needed hospitalisation during this period and 9 60; N0 = 516, N1 = 131, N2 = 121, M0 = 768; squamous = 417, adeno- (37.5%) patients received more than one antibiotic simultaneously. carcinoma = 301, large cell = 50; early LC = 214, invasive LC = 554. Sixty-two percent of patients were treated with beta-lactam-based Variables selected for 10YS study were 45 blood parameters, sex, age, antibiotics. The most common indication for antibiotic use was TNMG, cell type, tumor size. Cox modeling, SEPATH, Monte Carlo, respiratory tract infection (87.5%). We found a similar response rate, bootstrap, neural networks computing were used to determine any progression-free survival and overall survival for the two groups significant dependence. (patients with or without ATB) without statistically significant Results: Overall life span (LS) was 2244.9 ± 1750.3 days and 5-year differences. survival (5YS) reached 72.9%, 10YS – 64.3%, 20 years – 43.1%. 502 Conclusions: In our study, antibiotic use was not associated with worse lived more than 5 years, 145 – more than 10 years.199 died because of outcomes in patients treated with ICI. Despite recent studies had shown LC (LS = 562.7 ± 374.5 days). AT significantly improved 10YS (52.4% vs. a worse prognosis with previous ATB administration, this relation is not 27.7%) (P = 0.000 by log-rank test) only for LCP with N1-2. Cox well stablished. Prospective studies are required to validate these modeling displayed that 10YS significantly depended on: phase findings. transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, Legal entity responsible for the study: The authors. cell ratio factors-CRF (ratio between cancer cells- CC and blood cells Funding: Has not received any funding. subpopulations), G1-3, histology, glucose, AT, blood cell circuit, Disclosure: All authors have declared no conflicts of interest. prothrombin index, heparin tolerance, recalcification time, weight, color index (P = 0.000–0.039). Neural networks and bootstrap simulation revealed relationships between 10YS and PT early-invasive LC (rank 212P_PR — = 1), thrombocytes/CC (2), PT N0 N12 (3), segmented neutrophils/CC, Language and understanding: The complexity of insight in healthy cells/CC, lymphocytes/CC, erythrocytes/CC, stick neutrophils/ cancer care CC, eosinophils/CC, leucocytes/CC. Conclusions: 10-Year survival of LCP after radical procedures signifi- T. Martin1,D.O’Doherty1, C. Mattisa1, T. Byrne1, R. Keogh1, cantly depended on: PT early-invasive cancer; PT N0–N12; CRF; blood C. Murphy1, P. Bredin1, S. Devanney1, P.G. Morris1, B. Hennessy1, cell circuit; biochemical factors; hemostasis system; AT; LC character- L. Grogan1, O.S. Breathnach2,R.O’Dwyer1 1Medical Oncology, istics; anthropometric data; surgery type. Optimal diagnosis and Beaumont Hospital, Dublin, Ireland; 2Beaumont Hospital, Dublin, Ireland treatment strategies for LC are: screening and early detection; availability of experienced thoracic surgeons because of complexity of Background: Globalisation has led to an increase in immigration as procedures; aggressive en block surgery and adequate lymphadenect- some pursue the potential for a more financially secure life away from omy for completeness; precise prediction; AT for LCP with unfavorable their country of birth. This leads to an increase in a nation’s linguistic prognosis. diversity. In Ireland one of the official languages is English and the Legal entity responsible for the study: Oleg Kshivets. prevalence of fluency in other languages within the Irish-born Funding: Has not received any funding. population is modest. We sought to assess language challenges within Disclosure: The author has declared no conflicts of interest. our patients with limited English proficiency to gain insight into the distribution of languages and social circumstances of this population, as well as patterns of use of formal interpreter services. Methods: Data was obtained from the formal interpreter service and from the coordinating social workers to identify patients with limited English proficiency. Inclusion was based on documented evidence of S812 Journal of Thoracic Oncology Vol. 16 No. 4S limited English proficiency in medical oncology patients. Included thrombosis. VTE occurrence did not correlate with the prognosis. Further patients had data collected on diagnosis, treatment regimen, primary and prospective studies are needed to derive definitive conclusions. language, use of interpreter services, and social circumstances. Legal entity responsible for the study: The authors. Population data was from the 2016 Irish Census. Funding: Has not received any funding. Results: 242 interpreter referrals were arranged from Nov. 2017 to Dec. Disclosure: All authors have declared no conflicts of interest. 2020. Screening included 102 patients of which 26 were excluded as the level of English proficiency was not documented or they did not attend the Oncology Service. The number of interpreter requests ranged from 0 214P to 18 per patient. The top languages were: Russian (18%), Lithuanian The role of USS guided biopsy in the investigation of lung (11%), Romanian (10%), Polish (9%). The population of Ireland cancer measured 4,761,865 in 2016. “Foreign born” residents account for 17% of the Irish population; this group mainly come from Mid/Eastern A. Aujayeb1, C. Storey2, P. Narkhede2, E. Hill2, M. Carling2 Europe (Polish: 122,515; UK: 103,113; Lithuanian: 36,522; Romanian: 1Respiratory Medicine, Northumbria HealthCare NHS Foundation Trust, “ ” 29,186; Latvian: 19,933) apart from the UK. 75% of foreign born Newcastle, UK; 2Northumbria Healthcare NHS Foundation Trust, residents speak their primary language at home. Of these aged 65 years Newcastle, UK or more (n = 12,303) 20% reported having little or no English. Conclusions: With the growing complexity of therapeutic approaches in Background: Northumbria HealthCare NHS Foundation Trust, in the lung cancer therapy there is a predictable communication discordance North East of England, is a large centre with high volume of lung cancer between healthcare staff and patients with limited English proficiency. and mesothelioma. Services such as CT guided biopsy and local Strategies incorporating formal interpreters, staff members with diverse anaesthetic thoracoscopy are well established in the diagnostic linguistic skills and family members proficient in English may enhance pathway. For some patients, Ultrasound (USS) guided pleural or chest the communication with patients thereby improving their treatment wall biopsies also have a role to play. Retrospective reviews help in decisions. assessing diagnostic sensitivity and safety of such procedures. Legal entity responsible for the study: The authors. Methods: With local Caldicott approval, a retrospective review of all USS Funding: Has not received any funding. guided chest wall and pleural biopsies was performed. Basic demo- Disclosure: All authors have declared no conflicts of interest. graphics were collected, as well as size of needle, presence of complications, need for re-biopsy and overall pathological diagnoses. The time frame was Jan 2010–Nov 2020. Results: 50 patients were identified. Mean age was 75.6 years (range 213P 48–92). 21 patients were female, and 29 male. 25 had pleural biopsies Incidence of venous thromboembolic events in lung cancer and 25 chest wall and/or rib biopsies. A 14Fg needle was used in 1 patients receiving immunotherapy: A single-institution patient, 16Fg in 9, 18 Fg in 36, 20 Fg in 1 and there was no data available experience in 3 patients. 49 patients had no immediate complications to the procedure, and none within 30 days either. One patient had an attempt at L. Gutierrez Sainz, P. Cruz Castellanos, D. Sanchez Cabrero, pleural biopsy but only liver tissue was obtained, probably due to the O. Higuera Gomez, J. De Castro Carpeno Medical Oncology needle inadvertently crossing the diaphragm, as the biopsy did not use Department, Hospital Universitario La Paz, Madrid, Spain real time guidance. 5 biopsies were non-diagnostic, 3 pleural biopsies, 1 Background: Lung cancer and lung cancer therapies such as chest wall and 1 rib biopsy. 1 required a re-biopsy, 1 required a bronchoscopy and 3 were not investigated further. Overall diagnostic chemotherapy and antiangiogenic agents have been associated with an sensitivity is 90%, 88% for pleural biopsies and 92% for chest wall/rib increased incidence of venous thromboembolic events (VTE). However, the incidence of VTE in lung cancer patients on immunotherapy has not biopsies. Diagnoses included 13 mesotheliomas, 2 renal cancers, 19 lung cancers, 1 breast cancer, 1 gastro-intestinal cancer, 6 chronic fibrinous been well characterized. The aim of this study was to assess the incidence of VTE in lung cancer patients receiving immunotherapy and pleuritis, 2 lymphomas and 1 cancer of unknown primary. Conclusions: Overall, the local USS guided biopsy service is safe and has ascertain its prognostic utility. high sensitivity. We have easy access to CT guided biopsy and medical Methods: We conducted a single-institution retrospective study, including all lung cancer patients treated with anti-Programmed cell thoracoscopy and thus do not need to perform USS procedures often. We have set up guidance that real time ultrasound guidance should be used Death 1 (PD-1), anti-Programmed cell Death Ligand-1 (PD-L1), a combination of anti-PD-1/anti-PD-L1 and anti-CTLA4 or a combination for every procedure rather than pre-procedural guidance only. including any of these drugs with chemotherapy, antiangiogenic agents Legal entity responsible for the study: The authors. Funding: Has not received any funding. or both between June 2013 and April 2019 at La Paz University Hospital, Madrid (Spain). Disclosure: All authors have declared no conflicts of interest. Results: We selected 110 patients. The majority (n = 79, 71.8%) were males with a median age of 66 years (range 43–86 years). Most patients (m = 106, 96.4%) had stage IV at the beginning of immunotherapy 215P treatment. 9 of 110 patients (8.2%) were under use of blood thinners. The feasibility of day case thoracoscopy Pembrolizumab monotherapy was the agent most commonly used (n = 59, 53.6%) and nivolumab plus ipilimumab was the most common A. Aujayeb1, E. Hill2 1Respiratory Medicine, Northumbria HealthCare multidrug regimen (n = 7, 6.4%). VTE occurred in 10 of 110 patients NHS Foundation Trust, Newcastle, UK; 2Northumbria Healthcare NHS (9.1%). Female sex was independently associated with an increased risk Foundation Trust, Newcastle, UK of VTE (OR 6.11 [95%CI: 1.31–28.40], p = 0.02). 7 of 10 VTE (70%) were symptomatic. Progressive disease to immunotherapy (HR 17.06 [95%CI: Background: Northumbria Healthcare NHS Foundation Trust runs a 6.03–48.26], p = 0.00) was independently associated with shorter OS. very successful pleural service catering for patients with malignant VTE occurrence was not independently associated with shorter OS (HR pleural fluid, pleural infection and pneumothorax. Local anaesthetic 1.43 [95%CI: 0.45–4.49], p = 0.53). medical thoracoscopy (LAT) is a well-established diagnostic, therapeutic Conclusions: In our cohort, the incidence of VTE in lung cancer patients and preventative procedure in undiagnosed pleural effusions. Patients receiving immunotherapy was low. Female sex was a risk factor for were traditionally admitted for a mean of 3.4 days and had a large bore drain inserted post LAT and pleurodesis was performed. The Covid-19 April 2021 Abstracts S813 pandemic has forced us to provide day case LAT with IPC placement viability of NSCLC, with enhanced death after exposure to DNA- without pleurodesis to minise transmission risk. We thus describe our damaging-agents. Bioinformatic analyses further demonstrated that local experience. LAT is performed in theatre under conscious sedation. COMMD1 levels positively correlate with the gene ontology DNA repair Methods: All the notes of patients requiring day case LAT between July gene set enrichment signature in NSCLC. 2020-Dec 2020 were analysed. Basic demographics were collected as Conclusions: Taken together, our data suggests COMMD1 functions in well as diagnoses and what interventions were performed. A descriptive the DNA damage response and is a potential therapeutic target and analysis of the data was performed. diagnostic biomarker in NSCLC, through the induction of cell death and Results: 13 patients underwent day case LAT. All had negative pre- inhibition of tumour growth. operative Covid-19 swabs. Mean age was 69.7 years (range 24–82). 10 Legal entity responsible for the study: The authors. were male and 3 female. Definite diagnoses included 5 lung cancers, 4 Funding: Yancoal; William and Hilde Chenhall Research Trust Research mesotheliomas and 2 fibrinous pleuritis. The lung did not deflate, not Award. allowing for biopsies in 2 patients. Non-malignant diagnoses are Disclosure: All authors have declared no conflicts of interest. currently presumed. 10 IPCs and 1 large bore drain were inserted due to 1 immedidate complication (surgical emphysema). 1 patient developed an empyema within 30days. 8 out of the 10 IPCs have 217P already been removed due to pleurodesis occuring (mean number of Circulating microRNA21 and microRNA126: Diagnostic, days 27.5, range 16–72). All patients were discharged on the same day prognostic value and multivariate analysis in non-small except 1 patient who required a large bore drain and stayed overnight. Conclusions: We have thus transformed our service after more than a cell lung cancer decade of providing LAT as an inpatient service. This is a small cohort of A.M. Alhanafy1, S. Soliman2, A. Abdelaleem3, A. Abo Elhaded4, patients but proves the feasibility and safety of day case LAT with 4 5 1 massive reduction in inpatient stay. The Covid-19 pandemic has M. Assar , R. Ibrahem Clinical Oncology and Nuclear Medicine Dept, transformed our service but for the better. Further qualitative work MFM - Menoufia University - Faculty of Medicine, Shebeen El-Kom, Egypt; 2Medical Biochemistry and Molecular Biology, MFM - Menoufia should elucidate the acceptability of such a pathway for patients. 3 Legal entity responsible for the study: The authors. University - Faculty of Medicine, Shebeen El-Kom, Egypt; Medical Biochemistry Unit Department of Pathology, College of Medicine, Qassim Funding: Has not received any funding. 4 Disclosure: All authors have declared no conflicts of interest. University, Qassim, Saudi Arabia; Chemistry Department, Faculty of Science - Menoufia University, Shebeen Elkom, Egypt; 5Department of Public Health and Community Medicine, MFM - Menoufia University - Faculty of Medicine, Shebeen El-Kom, Egypt 216P COMMD1 in non-small cell lung cancer: A novel DNA repair Background: One of the most recent approaches of tumor molecular protein as a therapeutic target and diagnostic biomarker characterization is mainly based on microRNA expression profile. No single marker is sufficiently accurate for clinical use and multiple A. Suraweera1, P. Duijf2, M. Tang1, C. Jekimovs1, K. Schrobback1, biomarker panels are developed for three main purposes tumor subtype C. Liu3, M. Adams1, D. Richard1,K.O’Byrne1 1School of Biomedical classification, early detection and prediction of tumor responses to Sciences, Queensland University of Technology, Brisbane, Australia; treatment and prognosis of patients. Micro- 21 and Micro-126 have 2Queensland University of Technology, Brisbane, Australia; 3QIMR received special attention because of their relationship with many Berghofer Medical Research Institute, Brisbane, Australia cancer sites we aimed to study their diagnostic and prognostic utility in lung cancer patients. Background: Lung cancer has the highest incidence and mortality Methods: 100 subjects classified into two groups: group 1 comprised 60 among all cancers. As resistance to the current therapies are inevitable, Lung cancer patients, and group II comprised 40 age- and sex-matched there is a great need to identify new therapeutic targets. To prevent volunteers, Real-time PCR of micro RNA 21 and 126 were done and cancers, cells possess a complex system of signalling pathways called the studied in control and patients to detect diagnostic utility and correlated DNA damage response, which is involved in the detection, signalling, and with all disease clinicopathological data and patients survival. subsequent repair of DNA. Failure of the DNA damage response leads to Results: Higher miR-21 and lower miR-126 levels were found in lung cancer and tumorigenesis. The aims of this study were to investigate the patients than in controls. The sensitivity of CEA and miR-21 and miR- function of COMMD1 in the DNA damage response and additionally as a 126 (78.3%, 96.7%, 90%) at cutoff points (7.5, 2.35, 2.175) respectively prognostic and therapeutic target in non-small cell lung cancer (NSCLC). to distinguish NSCLC patients from controls. On combining both Methods: COMMD1 function in DNA repair was investigated using microRNA21 & microRNA 126 an improvement of sensitivity to 97% reporter assays in COMMD1-siRNA-depleted cells, in vitro binding was noted. For patients, miR-21 increased significantly with metastatic assays and using molecular dynamic simulations. The expression of stage and highest grade GIII. Regarding survival there was significantly COMMD1 in NSCLC was investigated using bioinformatic analysis, qRT- longer overall survival among patients with more early stages and lower PCR and immunoblotting of control and NSCLC cell lines, lung cancer grades GI &II and with low Micro- 21 and high micro-126. On Cox tissue microarrays, cell viability and cell cycle experiments. regression analysis for independent prognostic factors of survival; Results: Reporter assays demonstrated that COMMD1 functions in the micro-126 and presence of metstases were the independent factor for repair of DNA double strand breaks and in vitro binding assays and survival with hazard ratio 0.26 (95% CI 0.06–1.09) 3.64 (95% CI 1.22– molecular dynamic simulations confirmed the binding of COMMD1 and 16.5) respectively. the DNA repair protein Chk2. Bioinformatic analysis showed that Conclusions: CirculatorymiR-21 and miR-126 may play significant role COMMD1 is upregulated in NSCLC, with high levels of COMMD1 in diagnosis and prognosis in NSCLC patients. associated with poor patient prognosis. COMMD1 mRNA and protein Legal entity responsible for the study: Menoufia University. were upregulated across a panel of NSCLC cell lines and siRNA-mediated Funding: Has not received any funding. depletion of COMMD1 decreased cell proliferation and reduced cell Disclosure: All authors have declared no conflicts of interest. S814 Journal of Thoracic Oncology Vol. 16 No. 4S

plasma. Clinical records of 41 patients were available. The table shows 218P the type of first-line treatment and response rates in 35 advanced Clinical characteristics and treatment outcomes in lung patients. Only 12 patients received second-line of treatment. mOS was – cancer patients with FGFR genes alterations 25.0 months (CI 95%: 17.1 32.8) and mSLP was 9.0 months (CI 95%: 0.0–19.4). ́ 1 1 1 J. Torres Jimenez , J. Esteban Villarrubia , E.M. Vida Navas , Table 218P J.J. Soto Castillo1, L. Sanz Gómez1, I. Orejana Martıń1, P. Álvarez Ballesteros1, J. Pozas Pérez1, M. San Román Gil1, Stable Complete V. Albarrán Fernández1, J. Chamorro Pérez1, D.I. Rosero Rodrıgueź 1, Type of Progression disease response treatment n (%) (%) (%) (%) A. Gómez Rueda1, E. Corral de la Fuente1, Y. Lage1, A. Santón2, A. Benito Berlinches2, M. Lario2, M.E. Olmedo Garcıá1, CT 21 (44.7) 16 (45.7) 3 (8.5) 0 P. Garrido Lopez1 1Medical Oncology Department, Hospital IT 9 (21.5) 3 (8.5) 5 (14.2) 1 (2.8) Universitario Ramon y Cajal, Madrid, Spain; 2Pathology Department, CT + IT 5 (10.6) 4 (11.4) 0 0 Hospital Universitario Ramon y Cajal, Madrid, Spain FGFR mutations were the most frequent molecular alterations (FGFR1 Background: Lung cancer (LG) is characterized by numerous genomic (48.9%), FGFR2 (27.7%) and FGFR3 (19.1%)), although only 38.5% alterations although so far targeted agents have been approved only for were described as pathogenic (50% in tissue and 50% in plasma). some of them. FGFR genes alterations have been described in lung Amplification were found in 29.8% of patients (85.8% in tissue and in cancer patients but clinical characteristics and treatment outcomes are 14.2% plasma). FGFR was associated to EGFR, PIK3CA and KRAS not well known yet. mutations in 27 patients. No correlation was found between the type of Methods: A retrospective review of advanced LG patients with FGFR FGFR alteration and survival in the univariant analysis. Variants of FGFR alterations based on tissue or plasma NGS was performed to describe did not have association with sex, ECOG, histology, status of smoking, PD- clinical characteristics and treatment outcomes. L1, TMB and type of treatment. Results: Clinical characteristics of 47 identified were similar to other Conclusions: Our cohort did not show that FGFR genes alterations types of LG (61.7% male, median age 68 y, 70.2% former smokers, confer distinct clinical characteristics in LG patients. However, much 46.8% ECOG 0, 72.3% stage IV). Adenocarcinoma was the most frequent more investigation is needed. subtype (59.6%), then squamous (21.8%) and small cell (6.4%). PD-L1 Legal entity responsible for the study: The authors. >50% in 43.8% of patients and TMB was <10 in 58.3%. FGFR alterations Funding: Has not received any funding. were described in tissue NGS in 21 patients and “liquid” biopsy in 27 Disclosure: All authors have declared no conflicts of interest. patients. In two patients NGS were realized simultaneously on tissue and ABSTRACTS

AUTHOR INDEX

Aarts, M.J., S711 (30P) Assar, M., S813 (217P) Besse, B., S707 (22P), S719 (47P), S722 (50P), Abbosh, C., S745 (93TiP) Astara, G., S699 (2P) S752 (100MO), S764 (121P) Abdelaleem, A., S813 (217P) Atmaca-Dirik, H., S800 (189TiP) Betof Warner, A., S799 (187TiP) Abhi, D., S733 (71P) Atreya, S., S791 (170P) Bharati, S., S708 (23P) Abo Elhaded, A., S813 (217P) Attili, I., S754 (104P) Bhosle, J., S787 (163P), S795 (180P) Abonyi-Toth,́ Z., S718 (45P) Auclin, E., S707 (22P) Bigay-Game, L., S719 (47P) Aboubakar, F., S707 (22P) Audigier Valette, C., S757 (109P), S758 (110P) Bihl, M., S700 (4P) Abuladze, M., S717 (43P) Aujayeb, A., S807 (201P), S807 (202P), Bini, M., S797 (184P) Adams, M., S813 (216P) S812 (214P), S812 (215P) Bironzo, P., S773 (140P) Addeo, A., S761 (117P), S772 (138P) Aydin, E., S782 (156P) Bischoff, H.G., S737 (78MO) Adderley, H., S764 (121P) Aydiner, A., S782 (155P), S782 (156P) Bittner, N., S718 (45P) Aerts, J.G., S708 (24P) Azevedo, I., S809 (206P) Blackhall, F., S720 (48MO), S764 (121P) Agar, C., S794 (179P) Blanksma, A., S710 (28P) Agbarya, A., S738 (79MO) Baijal, S., S731 (67P) Bleckmann, A., S740 (82P) Agelaki, S., S705 (16P) Bailey, T., S770 (135P), S775 (143P), Boerckel, W., S810 (209P_PR) Agrawal, S., S750 (98O) S775 (144P) Bogos, K., S718 (45P) Aguado, M., S768 (131P) Bal, A., S790 (168P) Bonanno, L., S723 (51P), S763 (119P), Ahmed, H.S., S712 (33P) Baldi, S., S803 (195P) S779 (149P), S796 (181P) Ahn, H.K., S776 (145P) Baliou, E., S704 (14P) Bonito, N.A., S769 (132P) Ahn, J.S., S803 (193P) Balli, D., S750 (98O) Bonucci, C., S759 (113P) Ahn, M-J., S745 (93TiP), S803 (193P) Banfill, K., S808 (203MO) Boosman, R.J., S720 (48MO) Aix, S.P., S753 (103P) Bansal, R., S714 (38P) Borges, M., S735 (75P) Aktan, M., S727 (58P) Baptista, M.M., S806 (200P) Borghaei, H., S720 (48MO) Alagiyawanna, L.R., S712 (31P) Barabadze, D., S717 (43P) Borras,́ R., S805 (196P) Albarrań Fernandez,́ V.,S724 (52P),S814 (218P) Barabino, E., S802 (192TiP) Bortolami, A., S796 (181P) Aldanakh, A., S803 (195P) Barata, J., S806 (200P) Bosch-Barrera, J., S700 (3P) Aldea, M., S707 (22P), S764 (121P) Barba Joaquın,́ A., S768 (131P) Bote, H., S806 (198P) Al-Dubai, H., S803 (195P) Barcza, Z., S718 (45P) Boucher, M-E., S719 (47P) Alexandru, A., S750 (98O) Barlesi, F., S745 (93TiP) Boukovinas, I., S762 (118P) Alhanafy, A.M., S813 (217P) Barletta, L., S802 (192TiP) Boutmy, E., S785 (160P) Allen, A., S738 (79MO) Barneto Aranda, I.C., S740 (81P) Boyer, M., S720 (48MO) Almeida, S., S793 (176P), S811 (211P) Barradas, L., S734 (74P) Bozorgmehr, F., S725 (54P) Al-Najjar, H.M., S744 (91P) Bartels, M., S729 (61MO) Brahmer, J.R., S798 (185TiP) Alnusaif, M., S803 (195P) Barve, M., S751 (99O_PR) Brambilla, M., S769 (133P), S797 (184P) Alonso, G., S805 (196P) Baschnagel, A.M., S727 (58P) Branca, C., S704 (12P) Al-Radhi, M., S803 (195P) Basto, R., S743 (87P), S768 (130P) Brand, V., S729 (61MO) Álvarez Ballesteros, P., S701 (6P), S724 (52P), Batista, M.V., S811 (211P) Bratman, S., S736 (77TiP) S765 (124P), S814 (218P) Batra, U., S701 (5P), S715 (39P), S717 (44P) Bravo-Carmona, P., S735 (76P) Amat, R., S766 (126P), S767 (127P) Baucina, M., S701 (7P) Breathnach, O.S., S811 (212P_PR) Ambrosini, V., S756 (107P) Bauml, J.M., S699 (1P) Bredin, P., S811 (212P_PR) Ameen, M., S803 (195P) Bayarri-Lara, C.I., S735 (76P) Brega, N., S786 (162P) Amorim Costa, C., S768 (129P), S768 (130P), Bazhenova, L., S699 (1P), S751 (99O_PR) Bria, E., S754 (104P), S761 (117P) S769 (132P) Beattie, V., S810 (209P_PR) Brinkman, S., S733 (72P) Amrith, B., S717 (44P) Beckmann, G., S786 (162P) Britschgi, C., S783 (157P) Andric, Z.G., S753 (103P) Begum, F.A., S712 (33P) Britten, A., S808 (203MO) Angelaki, S., S762 (118P) Belka, C., S726 (57P), S741 (84P), S742 (85P) Brückner, L., S780 (153P) Ansmann, L., S710 (28P) Belting, M., S725 (55P) Brueckl, W.M., S740 (82P) Antigny, M., S752 (100MO) Bendahl, P-O., S725 (55P) Brunnström, H., S706 (18P) Antolin, C., S709 (26P) Benet, M., S788 (165P) Bruns, R., 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(51P) Assaf, J.D., S766 (126P), S767 (127P), Bernardo, F., S735 (75P) Calabro,̀ D., S756 (107P) S806 (198P) Bertolaccini, L., S744 (89P) Calcagno, F., S719 (47P)

Journal of Thoracic Oncology Vol. 16 No. 4S: S815–S824 S816 Journal of Thoracic Oncology Vol. 16 No. 4S

Caldeira, J.N., S734 (74P) Chouaid, C., S738 (79MO), S757 (109P), Dal Maso, A., S723 (51P), S763 (119P), Callejo, A., S766 (126P), S767 (127P), S758 (110P) S779 (149P) S806 (198P) Chou, T-Y., S770 (135P), S775 (143P), Damhuis, R., S703 (10P) Calles Blanco, A., S753 (103P) S775 (144P) D’Angelillo, R.M., S717 (42P) Camara, J.C., S808 (204P) Christensen, J.G., S751 (99O_PR) Daniel, A., S718 (45P) Caminoa Lizarralde, A., S724 (52P) Christoph, D., S738 (79MO) Dansin, E., S719 (47P) Campanini, N., S701 (7P) Christopoulos, P., S725 (54P), S762 (118P), Daoud, H., S776 (145P) Camps, C.J., S752 (100MO) S772 (139P), S780 (153P) Das, M., S773 (141P) Cang, S., S727 (60TiP) Chrystelle, C., S742 (86P), S809 (207P) Das, S., S712 (33P) Cantini, L., S713 (35P), S761 (117P) Church, M., S764 (121P) Davidson, M., S787 (163P), S795 (180P) Cao, B., S753 (102P) Chu, T., S726 (56P), S789 (166P) de Alvaro, J., S722 (50P) Cao, L., S727 (60TiP), S753 (102P) Ciaramella, V., S805 (196P) Debieuvre, D., S758 (110P) 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Cobo, M., S750 (98O), S760 (115P) de Langen, A., S703 (10P) Casal Rubio, J., S740 (81P) Codima, A., S764 (122P) de las Penas Bataller, R., S752 (100MO) Casarrubios, M., S740 (81P) Cognigni, V., S713 (35P) del Barco, E., S740 (81P) Castelo, B., S709 (26P) Cohen, D., S771 (136P) Della Corte, C.M., S789 (167P), S805 (196P) Castillo, S., S796 (182P) Colinet, B., S798 (186TiP) Delmonte, A., S737 (78MO) Catalano, F., S802 (192TiP) Colwell, H.H., S792 (173P) Del Rey-Vergara, R., S724 (53P) Cavic, M., S705 (17P) Compañ-Quilis, D., S805 (196P) Deltas, C., S709 (25P) Cedres, S., S766 (126P), S767 (127P), Compere, C., S790 (169P) de Marinis, F., S754 (104P) S806 (198P) Cona, M.S., S713 (35P) Demedts, I., S790 (169P), S798 (186TiP) Chaft, J., S745 (93TiP) Conci, N., S756 (107P), S759 (113P) De Miguel-Perez, D., S735 (76P) Chamorro Perez,́ J., S724 (52P), S814 (218P) Constantinou, A.I., S709 (25P) Demirkazık, A., S782 (155P) Champiat, S., S720 (48MO) Conte, P., S783 (157P) Demurtas, L., S699 (2P) Chandarana, K., S805 (197P) Conte, P.F., S723 (51P), S763 (119P), Dennis, P.A., S745 (93TiP) Chang, J., S778 (147P) S779 (149P), S796 (181P) Deo, S.V.S., S708 (23P) Chang, Q., S771 (137P) Conticelli, F., S705 (15P) de Petris, L., S729 (63MO) Chan, J.W.Y., S730 (64MO) Cordon, L., S788 (165P) Derijcke, S., S798 (186TiP) Chao, R.C., S751 (99O_PR) Corica, F., S755 (106P) de Ruiter, J., S703 (10P) Charalambous, H., S709 (25P) Corral de la Fuente, E., S701 (6P), De Ruysscher, D., S711 (30P) Chaturvedi, A., S717 (44P) S724 (52P), S765 (124P), S765 (125P), Desai, A., S707 (21P), S714 (38P) Chau, M., S770 (135P), S775 (143P), S814 (218P) Deschepper, K., S790 (169P) S775 (144P) Correia Magalhães, J., S743 (87P), S768 (130P) de Sousa, M.J.P., S743 (87P), S768 (130P) Chen, C-F., S761 (116P) Cortellini, A., S713 (35P), S761 (117P) De Toma, A., S769 (133P), S797 (184P) Chen, E., S727 (60TiP) Cortot, A., S783 (157P), S784 (158P), De Tursi, M., S761 (117P) Chen, G., S748 (96O), S799 (187TiP), S784 (159P) Devanney, S., S811 (212P_PR) S800 (188TiP) Costa, I., S764 (122P) De Vito, C., S772 (138P) Cheng, B., S732 (68P) Couch, D., S757 (109P) Diaz Mejia, N.M., S766 (126P), S767 (127P) Cheng, H., S704 (13P) Coulon, S.H., S790 (169P) Diaz Perez, I., S737 (78MO) Cheng, Y., S727 (60TiP), S748 (96O), S748 (97O) Courtinard, C., S757 (109P), S758 (110P) Dıaź Perez,́ I.E., S747 (95TiP) Chen, H., S703 (11P), S704 (13P) Coves Sarto, J., S752 (100MO) Dietzen, M., S704 (12P) Chen, J., S729 (62MO), S748 (96O), Cozzolino, I., S805 (196P) Dietz, L.A., S785 (160P) S793 (174P), S798 (185TiP) Crivellaro, G., S796 (181P) Di Federico, A., S759 (113P) Chen, J-Y., S786 (161P) Cruz-Bermudez, A., S740 (81P) Di Liello, R., S789 (167P), S805 (196P) Chen, P., S780 (152P) Cruz Castellanos, P., S709 (26P), S812 (213P) Di Maio, M., S761 (117P), S773 (140P), Chen, S., S759 (112P), S759 (114P), Cui, W., S787 (163P), S795 (180P) S789 (167P) S778 (148P), S779 (151P), S792 (172P) Cunanan, K.M., S773 (141P) Dima, L., S786 (162P) Chen, T.T., S773 (141P) Cunha Pereira, T., S768 (129P) Dimitriou, K., S725 (54P) Chenuc, G., S758 (110P) Cuppens, K., S790 (169P) Dingemans, A-M.C., S708 (24P) Chevallier, M., S772 (138P) Curtin, J., S699 (1P) Dinges, L-A., S725 (54P) Chiang, C-L., S761 (116P), S777 (146P) Czarnecka, K., S801 (191TiP) Di Pietro Paolo, M., S713 (35P) Chiari, R., S713 (35P) Dogan, I., S782 (155P), S782 (156P) Chiu, C-H., S760 (115P) Dal Bello, M.G., S802 (192TiP) Doger de Speville,́ B., S799 (187TiP) Choi, Y-L., S770 (135P), S775 (143P), D’Alessio, P., S717 (42P) Domine Gomez, M., S740 (81P), S775 (144P) Dall’Olio, F.G., S756 (107P) S752 (100MO) April 2021 Abstracts S817

Domingues, I., S743 (87P), S768 (129P), Felip Font, E., S753 (103P) Gervais, R., S758 (110P) S768 (130P), S769 (132P) Feller-Kopman, D., S788 (164P) Gettinger, S., S799 (187TiP) Donati, G., S759 (113P) Feng, H-J., S786 (161P) Gezelius, E., S725 (55P) Dong, G., S781 (154P) Feng, J., S779 (150P) Gezin, A., S784 (158P), S784 (159P) Dong, X., S727 (60TiP) Ferhatoğlu, F., S782 (155P), S782 (156P) Ghafoor, Q., S731 (67P) Dong, Y., S793 (174P) Fernandes, G., S806 (200P) Giampieri, R., S713 (35P) Doni, M., S802 (192TiP) Ferrara, R., S769 (133P), S797 (184P) Giannarelli, D., S754 (104P) Dorkhom, N., S780 (152P) Ferro, A., S763 (119P), S779 (149P) Giordano, F.M., S717 (42P) Dorrius, M., S714 (36P) Fiaz, R., S799 (187TiP) Girard, N., S699 (1P), S719 (47P), Dostu, Y., S794 (177P) Ficorella, C., S761 (117P) S738 (79MO), S758 (110P) Doval, D.C., S717 (44P) Figueiredo, S., S735 (75P) Girelli, L., S744 (89P) Dowlati, A., S720 (48MO) Filippi, A.R., S738 (79MO), S747 (95TiP) Giselvania, A., S774 (142P) Drilon, A., S786 (162P) Filleron, T., S757 (109P), S758 (110P) Giugliano, F.M., S733 (70P) Dubbink, E.J., S771 (136P) Filvaroff, E., S722 (50P) Giusti, R., S761 (117P) Duecker, K., S753 (103P) Fiore, M., S717 (42P) Gkikas, A., S805 (197P) Duell, T. H-G-F., S742 (85P) Flörsch, B., S741 (84P) Gnetti, L., S701 (7P) Duijf, P., S813 (216P) Follador, A., S779 (149P) Goldberg, Z., S799 (187TiP), S800 (188TiP) Du, Y., S714 (36P) Fonseca, A.L., S734 (74P) Gomez-Randulfe, M.I., S768 (131P) Dziadziuszko, R., S747 (95TiP) Forster, M.D., S810 (208P) Gomeź Rueda, A., S701 (6P), S724 (52P), Foster, S., S745 (92P) S765 (124P), S765 (125P), S814 (218P) Edelstein, D., S788 (164P) Fox, J., S810 (209P_PR) Gomez-Soler, M.C., S788 (165P) Ehrenstein, V., S730 (65P) Fragomeno, B., S756 (107P) Goncalves de Oliveira, K., S725 (55P) Ehrlich, A., S800 (189TiP) Franco, R., S805 (196P) Gonçalves-Monteiro, S., S735 (75P) Eichhorn, F., S725 (54P) Frega, S., S763 (119P), S779 (149P), Gonzalez-Castillo, L., S788 (165P) Eichkorn, T., S725 (54P) S796 (181P) Gonzalez-Gallardo,́ S., S724 (53P) Ek, L., S725 (55P) Freitas, R., S811 (211P) Gonzalez, H., S722 (50P) El-Habashy, D.M., S806 (199P) Friedlaender, A., S772 (138P) Gonzalez-Lopez, A., S808 (204P) Elmasry, A.R., S731 (67P) Frigola, J., S766 (126P), S767 (127P) Gonzalo, J., S806 (198P) Elshafie, R., S725 (54P), S762 (118P) Fukuda, M., S794 (177P) Goter, T., S794 (179P) Eppenberger-Castori, S., S700 (4P) Furedy, A., S780 (152P) Gottfried, M., S783 (157P) Ercan, C., S705 (15P) Govindan, R., S720 (48MO) Erefai, O., S713 (34P) Gaffly, G., S718 (45P) Goyal, J., S717 (44P) Eschmann, S., S739 (80P) Galassi, T., S713 (35P) Graf Finckenstein, F., S799 (187TiP), Esposito, G., S723 (51P), S789 (167P) Galetta, D., S754 (104P) S800 (188TiP) Esteban, M., S808 (204P) Galffy,́ G., S753 (103P) Grassi, M., S802 (192TiP) Esteban Villarrubia, J., S724 (52P), Galindo-Campos, M.A., S724 (53P) Gravina, A., S789 (167P) S814 (218P) Galli, G., S769 (133P), S797 (184P) Greco, C., S717 (42P) Estevinho, F., S702 (9P) Gallo, C., S789 (167P) Gregg, J., S770 (135P), S775 (143P), Evans, T., S733 (71P) Gallo, W., S725 (55P) S775 (144P) Evers, J., S711 (30P) Gamit, P., S708 (23P) Gregoriou, G., S709 (25P) Eze, C., S726 (57P), S741 (84P), S742 (85P) Ganzinelli, M., S797 (184P) Greillier, L., S722 (50P), S798 (186TiP) Gao, B., S727 (60TiP) Greuter, M.J.W., S714 (36P) Fabbri, F., S756 (107P) Gao, M., S727 (60TiP) Gridelli, C., S789 (167P) Fabre, C., S757 (109P) Gao, W., S801 (190TiP) Griesinger, F., S710 (28P), S741 (83P), Faehling, M., S739 (80P), S740 (82P), Garassino, M.C., S737 (78MO), S738 (79MO), S743 (88P), S770 (135P), S772 (139P), S780 (153P) S769 (133P), S783 (157P), S797 (184P) S775 (143P), S775 (144P), S780 (153P) Faivre-Finn, C., S722 (49MO), S737 (78MO), Garcia, A., S784 (158P), S784 (159P) Groen, H.J.M., S714 (36P) S808 (203MO) Garcia Campelo, M.R., S740 (81P), Grogan, L., S811 (212P_PR) Falcoz, P., S719 (47P) S747 (95TiP), S768 (131P) Grohe,́ C., S780 (153P), S800 (189TiP) Falkenstern-Ge, R.F., S780 (153P) Garcia-Diaz, A., S735 (76P) Grønberg, B.H., S729 (63MO) Falk, M., S772 (139P) Garcıá Pardo de Santayana, M., S801 (191TiP) Grossi, F., S761 (117P) Fallscheer, S., S739 (80P) Garcia-Sanchez, J., S788 (165P) Growcott, S.A., S745 (92P) Fang, J., S753 (102P) Garde-Noguera, J., S788 (165P) Gu, A., S789 (166P) Fang, M-Y., S786 (161P) Gardner, R.M., S773 (141P) Guarneri, V., S723 (51P), S763 (119P), Fang, Y., S748 (96O) Gargiulo, P., S789 (167P) S779 (149P), S796 (181P) Fan, L., S714 (36P) Garg, M., S790 (168P) Guezel, G., S753 (103P) Fanti, S., S756 (107P) Garitaonaindia, Y., S740 (81P) Guggenberger, J., S741 (84P) Fan, X., S726 (56P) Garrido Lopez, P., S701 (6P), S724 (52P), Guida, C., S733 (70P) Fan, Y., S727 (60TiP), S753 (102P), S765 (124P), S765 (125P), S814 (218P) Gunasekera, D., S712 (31P) S778 (147P) Gazzah, A., S707 (22P), S752 (100MO) Guo, H., S703 (11P) Fardis, M., S799 (187TiP), S800 (188TiP) Gebbia, V., S789 (167P) Guo, Q., S727 (60TiP) Farooqi, S., S729 (63MO) Gelibter, A.J., S754 (104P), S761 (117P), Guo, R., S748 (96O), S801 (190TiP) Fassan, M., S723 (51P) S769 (133P) Gürbüz, M., S782 (155P) Faull, I., S787 (163P) Gelsomino, F., S759 (113P) Gutierrez Sainz, L., S709 (26P), S812 (213P) Fedeli, A., S802 (192TiP) Genin, M., S798 (186TiP) Felip, E., S750 (98O), S766 (126P), Genova, C., S802 (192TiP) Haakensen, V.D., S738 (79MO) S767 (127P), S783 (157P), S806 (198P) Georgoulias, V., S704 (14P) Hackanson, B., S780 (153P) S818 Journal of Thoracic Oncology Vol. 16 No. 4S

Hadisurya, A., S742 (86P), S809 (207P) Indraccolo, S., S723 (51P), S779 (149P) Kelly, D.C., S736 (77TiP), S801 (191TiP) Haefliger, S., S799 (187TiP) Insa, A., S740 (81P), S805 (196P) Keogh, R., S811 (212P_PR) Hallqvist, A., S729 (63MO) Ippolito, E., S717 (42P) Kerjouan, M., S719 (47P) Halmos, B., S748 (97O) Iranzo, P., S766 (126P), S767 (127P), Khanmammadov, N., S782 (156P) Hami, H., S713 (34P) S806 (198P) Khatun, N., S712 (33P) Han, B., S706 (20P), S727 (59P), Irura, T.W., S718 (46P) Kheoh, T., S751 (99O_PR) S752 (101MO), S758 (111P), S789 (166P) Irwin, A., S731 (67P) Kim, H., S803 (193P) Hao, X., S781 (154P) Ishrat, N., S712 (33P) Kim, H.R., S760 (115P) Harada, G., S764 (122P) Islam, M.R., S712 (33P) Kiss, Z., S718 (45P) Harada, H., S727 (58P) Islam, M.R.R., S712 (33P) Klinakis, A., S704 (14P) Hardy-Werbin, M., S724 (53P) Iype, R., S722 (49MO) Klomp, H., S703 (10P) Hariyanto, T.I., S742 (86P), S774 (142P) Izumi, H., S720 (48MO) Kluger, H., S799 (187TiP) Harpole, D., S745 (93TiP) Kosmidis, P., S762 (118P) Hartemink, K., S703 (10P) Jagasia, M., S799 (187TiP), S800 (188TiP) Kotsakis, A., S704 (14P) Hasan, A.T.M.K., S712 (33P) Jain, A., S731 (67P) Koyi, H., S729 (63MO) Hashemi Sadraei, N., S720 (48MO) Jain, D., S708 (23P) Krebs, M., S764 (121P) Hatton, M., S808 (203MO) Jain, P., S715 (39P) Krisam, J., S762 (118P), S780 (153P) Heeg, B., S784 (158P), S784 (159P) Jajodia, A., S717 (44P) Krull, J., S707 (21P) Heinzelmann, F., S739 (80P) Jakobsen, E., S730 (65P) Kruser, T.J., S727 (58P) Heist, R.S., S751 (99O_PR) Jankovic, R., S705 (17P) Kshivets, O., S811 (210P) He, J., S732 (68P), S753 (102P) Jänne, P.A., S751 (99O_PR) Kumar, D., S701 (5P) He, K., S799 (187TiP) Janning, M., S780 (153P) Kumar, S., S708 (23P) He, Q., S732 (68P) Janssen, S., S727 (58P) Kummar, S., S786 (162P) Helbekkmo, N., S729 (63MO) Janssens, A., S790 (169P) Kuo, C-H., S761 (116P), S777 (146P) Helland, Å., S729 (63MO) Jares, P., S796 (182P) Kuon, J., S725 (54P) Hendriks, L., S711 (30P) Jaruseski, E., S733 (72P) Kurniawan, A., S742 (86P), S759 (112P), Hennessy, B., S811 (212P_PR) Jegannathen, A., S731 (67P), S808 (203MO) S759 (114P), S774 (142P), S778 (148P), Hennink, M., S810 (209P_PR) Jekimovs, C., S813 (216P) S779 (151P), S792 (172P), S809 (207P) Heriyanto, R.S., S742 (86P), S759 (112P), Jesus, E., S743 (87P), S768 (129P), Ky Ng, C., S705 (15P) S759 (114P), S778 (148P), S779 (151P), S768 (130P), S769 (132P) S792 (172P), S809 (207P) Jeyakumaran, N., S712 (31P) Labianca, A., S797 (184P) Hernando, S., S808 (204P) Jimeno, A., S799 (187TiP) Lacroix, L., S707 (22P) Herth, F., S725 (54P), S762 (118P) Jin, B., S793 (174P) Lage, Y., S701 (6P), S724 (52P), S765 (124P), Heukamp, L.C., S741 (83P), S772 (139P) Johansson, M., S729 (63MO) S765 (125P), S814 (218P) Heussel, C-P., S725 (54P) Johne, A., S783 (157P), S785 (160P) Lahoz, A., S788 (165P) Heuvelmans, M.A., S714 (36P) Johnson, M., S720 (48MO), S751 (99O_PR) Lai, E., S699 (2P) Hiep, D.T., S714 (37P) John, T., S750 (98O) Lai, V., S720 (48MO) Higuera Gomez, O., S709 (26P), S812 (213P) Jokic, V., S705 (17P) Lamba, M., S722 (50P) Hill, E., S812 (214P), S812 (215P) Jones, F., S788 (164P) Lamberts, V., S707 (22P) Hiroshi, G., S794 (177P) Jönsson, M., S706 (18P) Lario, M., S701 (6P), S724 (52P), S765 (124P), Holtrup, F., S788 (164P) Joseph, N., S712 (31P) S765 (125P), S814 (218P) Honda, N., S794 (177P) Jost, P.J., S704 (12P) Lassen, U., S786 (162P) Hondelink, L., S771 (136P) Jovelet, C., S707 (22P) Lau, R.W., S730 (64MO) Hong, J-L., S780 (153P) Juan-Vidal, O., S722 (50P), S750 (98O), Lavaud, P., S707 (22P) Horn, M.K., S792 (173P) S753 (103P), S788 (165P) La Verde, N., S713 (35P) Hossain, A., S712 (33P) Julian, G., S764 (122P) Law, J., S736 (77TiP), S801 (191TiP) Hossen, M.N., S712 (33P) Jung, H.A., S776 (145P), S803 (193P) Lawson, C., S733 (72P) Hsia, T-C., S761 (116P), S776 (145P), Junior, G.D.C., S764 (122P) Laza-Briviesca, R., S740 (81P) S777 (146P) Jürgens, J., S798 (186TiP) Lee, A.J.X., S810 (208P) Huang, D., S727 (60TiP) Lee, C.L., S808 (203MO) Huang, Y., S748 (96O) Kaderbhai, C., S757 (109P), S758 (110P) Lee, S., S748 (97O), S760 (115P), Hui, R., S770 (135P), S775 (143P), Kaesmann, L., S741 (84P) S799 (187TiP) S775 (144P) Kahangire, D.A., S770 (135P), S775 (143P), Lee, S-H., S803 (193P) Hu, J., S753 (102P) S775 (144P) Lee, S.H., S776 (145P) Hu, M., S706 (20P), S758 (111P) Kalantari, A., S765 (123P) Lee, S-M., S810 (208P) Hu, S., S748 (96O) Kalapanida, D., S705 (16P) Lee, S.S., S776 (145P) Hu, X., S755 (105P), S756 (108P) Kaliyamurthi, K., S793 (175P) Lee, Y.C., S776 (145P) Hummel, H-D., S720 (48MO) Kanaki, Z., S704 (14P) Le Guen, Y., S794 (179P) Hung, J-Y., S761 (116P), S776 (145P), Kanesvaran, R., S803 (195P) Leighl, N., S736 (77TiP), S770 (135P), S777 (146P) Kapoor, R., S790 (168P) S775 (143P), S775 (144P), S801 (191TiP) Huo, D.H., S729 (62MO) Karim, M.N., S712 (33P) Leitão, M., S809 (206P) Hurtado, A., S808 (204P) Karin, M., S741 (84P) Lei, X., S803 (194P) Hussain, S., S712 (32P) Karkera, J., S699 (1P) Le, L.W., S736 (77TiP), S801 (191TiP) Kashiura, D., S764 (122P) Lena, H., S757 (109P), S758 (110P), Ibañez, I., S709 (26P) Kasmann,L.,S726(̈ 57P),S727(58P),S742(85P) S794 (179P), S798 (186TiP) Ibrahem, R., S813 (217P) Kathmann, L., S710 (28P) Leonetti, A., S701 (7P) Impera, V., S699 (2P) Kavtaria, M., S717 (43P) Leventakos, K., S714 (38P) April 2021 Abstracts S819

Levin, L., S797 (183P) Madan, K., S708 (23P) McGranahan, N., S704 (12P) Le, X., S783 (157P) Maddalo, M., S802 (192TiP) Meadows-Shropshire, S., S750 (98O) Leyvraz, S., S786 (162P) Madeddu, C., S699 (2P) Medgyasszay, B., S748 (97O) Liang, H., S732 (68P) Magalhães, A., S806 (200P) Mehta, A., S701 (5P), S715 (39P), S717 (44P) Liang, S-Q., S706 (19P) Magalhães, D., S702 (9P) Meira Garcia, A.R., S768 (129P), S768 (130P), Liang, W., S732 (68P) Magalhães, H., S702 (9P) S769 (132P) Liang, X., S746 (94TiP) Mahadevia, P., S699 (1P), S792 (173P) Meister, M., S762 (118P) Li, C., S732 (68P) Maione, P., S789 (167P) Melander, O., S725 (55P) Licour, M., S738 (79MO) Majem Tarruella, M., S740 (81P), S760 (115P), Menezes, J., S750 (98O) Liersch, S., S725 (54P) S768 (131P) Meng, S., S711 (29MO) Lievens, Y., S791 (171P) Ma, K., S781 (154P) Menis, J., S763 (119P), S779 (149P), Li, F.X., S729 (62MO) Ma, Y., S702 (8P), S703 (11P), S746 (94TiP) S796 (181P) Li, H., S711 (29MO) Makin, R., S770 (135P), S775 (143P), Mentrasti, G., S713 (35P) Li, J., S703 (11P), S731 (66P), S781 (154P), S775 (144P) Meyer zum Büschenfelde, C., S740 (82P) S801 (190TiP) Makrythanasis, P., S704 (14P) Mezquita, L., S707 (22P), S796 (182P) Linardou, H., S762 (118P) Malik, P., S708 (23P) Mielgo Rubio, X., S709 (26P), S808 (204P) Lindberg, K., S729 (63MO) Mallio, C.A., S717 (42P) Migliorino, M.R., S761 (117P) Lindberg, L., S729 (63MO) Malwinder, S.S., S794 (178P) Milner-Watts, C., S787 (163P), S795 (180P) Lindsay, C., S764 (121P) Manapov, F., S726 (57P), S741 (84P), Minari, R., S701 (7P) Ling, X., S752 (101MO) S742 (85P) Minchom, A.R., S699 (1P), S787 (163P), Lin, H.M., S780 (153P) Manca, F., S699 (2P) S795 (180P) Lin, J., S786 (162P) Mancuso, G., S789 (167P) Misch, D., S780 (153P) Li, Q., S711 (29MO) Manglaviti, S., S769 (133P), S797 (184P) Missy, P., S719 (47P) Li, R., S744 (90P) Mankor, J., S708 (24P) Miura, S., S776 (145P) Li, S., S727 (60TiP) Mann, H., S745 (93TiP) Moeed, Y., S803 (195P) Li, T., S792 (173P) Marcella, E., S759 (112P), S759 (114P), Mohammed, T., S707 (21P) Li, X., S748 (96O) S778 (148P), S779 (151P), S792 (172P) Mokhtari, A., S713 (34P) Li, Y., S714 (36P), S755 (105P), S756 (108P) Marchese, P., S756 (107P) Moldvay, J., S718 (45P) Liscia, N., S699 (2P) Marchetti, A., S770 (135P), S775 (143P), Molina, T., S719 (47P) Listi, A., S773 (140P) S775 (144P) Moliner, L., S724 (53P) Liu, A., S727 (60TiP), S778 (147P) Marchetti, P., S769 (133P) Monastirioti, A., S705 (16P) Liu, C., S813 (216P) Marin, E., S796 (182P) Monkhorst, K., S703 (10P), S771 (136P) Liu, C-C., S748 (97O) Marinkovic, M., S705 (17P) Montebello, M., S755 (106P) Liu, F., S798 (185TiP) Markou, A., S704 (14P) Monteiro, G., S764 (122P) Liu, J., S803 (195P) Marmolejo, D., S766 (126P), S767 (127P), Monteiro, J.C., S743 (87P), S768 (129P), Liu, K., S792 (173P) S806 (198P) S768 (130P), S769 (132P) Liu, M., S704 (13P) Märten, A., S776 (145P) Montella, M., S805 (196P) Liu, S., S714 (36P) Martin, A-L., S758 (110P) Monton, V., S806 (198P) Liu, S.V., S756 (108P) Martinelli, E., S713 (35P) Moon, H., S709 (27P) Liu, W., S753 (102P) Martınez,́ C., S724 (53P) Moon, J., S709 (27P) Liu, W.R., S729 (62MO) Martinez-Cabañes, R., S808 (204P) Morabito, A., S789 (167P) Liu, X., S801 (190TiP) Martinez-Cutillas, M., S740 (81P) Moran Bueno, M.T., S752 (100MO) Liu, Y., S753 (102P), S778 (147P), Martinez, D., S796 (182P) Moreno, D., S808 (204P) S801 (190TiP) Martinez-Marti, A., S740 (81P), S766 (126P), Moreno Garcia, V., S786 (162P) Liu, Z., S781 (154P) S767 (127P), S806 (198P) Morgillo, F., S713 (35P), S789 (167P), Locke, I., S795 (180P) Martin Garcia, E., S732 (69P) S805 (196P) Lodeweges, J.E., S729 (61MO) Martın-Martorell,́ P., S805 (196P) Mormile, M., S733 (70P) Lopez-Martin, A., S752 (100MO) Martin, T., S811 (212P_PR) Mornex, F., S738 (79MO) Lorente, D., S788 (165P) Mascaux, C., S776 (145P) Moro-Sibilot, D., S798 (186TiP) Lorenzi, M., S779 (149P), S796 (181P) Massa, E., S699 (2P) Morris, P.G., S811 (212P_PR) Lo Russo, G., S769 (133P), S797 (184P) Massard, C., S764 (121P) Morton-Gittens, J., S809 (205P) Los, J., S788 (164P) Massarelli, E., S800 (188TiP) Mosquera, J., S768 (131P) Losonczy, G., S753 (103P) Massuti Sureda, B., S740 (81P), S752 (100MO) Mountzios, G., S762 (118P) Lostes, J., S806 (198P) Mathias, S.D., S792 (173P) Moyano Rodriguez, M.J., S735 (76P) Lowy, I., S760 (115P) Matos, P., S734 (74P) Mukae, H., S794 (177P) Lu, J., S706 (20P) Matter, M.S., S700 (4P) Mukherjee, S., S720 (48MO) Lu, S., S750 (98O), S753 (102P), S778 (147P), Mattisa, C., S811 (212P_PR) Muley, T., S762 (118P) S786 (161P) Mattoo, S., S701 (5P) Müller, V., S718 (45P) Luo, L., S731 (66P) Mavroudis, D., S705 (16P) Munkhbaatar, E., S704 (12P) Luong, M.K., S810 (208P) May, R., S745 (93TiP) Muñoz, S., S796 (182P) Luzi, S., S794 (179P) Mazher, S., S803 (195P) Murphy, C., S811 (212P_PR) Lv, D., S727 (60TiP) Mazieres, J., S737 (78MO), S748 (97O), Murukesh, N., S731 (67P) Lyons, H., S787 (163P) S783 (157P), S784 (158P), S784 (159P) Lyubimova, S., S719 (47P) Mazzanti, P., S713 (35P) Nadal, E., S740 (81P) Mazzaschi, G., S701 (7P), S802 (192TiP) Nagy, B., S718 (45P) Macerelli, M., S761 (117P), S779 (149P) Mazzoni, F., S761 (117P) Nagy, R.J., S787 (163P) Mactier, K., S733 (71P) McDonald, F., S738 (79MO) Nakas, A., S805 (197P) S820 Journal of Thoracic Oncology Vol. 16 No. 4S

Naltet, C., S707 (22P) Papadaki, C., S705 (16P) Polonio, E., S700 (3P) Napoli, V.M., S773 (140P) Papadopoulos, K., S751 (99O_PR) Polo, V., S779 (149P) Nardo, G., S723 (51P) Pardo, N., S766 (126P), S767 (127P), Pomp, J., S729 (61MO) Nardone, V., S733 (70P) S806 (198P) Ponce Aix, S., S722 (50P) Narine, N., S744 (91P) Parisi, C., S759 (113P) Popat, S., S776 (145P), S787 (163P), Narkhede, P., S812 (214P) Park, C-K., S776 (145P) S795 (180P) Nathany, S., S715 (39P) Park, K., S803 (193P) Pope, T., S808 (203MO) Navani, N., S770 (135P), S775 (143P), Park, S., S803 (193P) Porta-Balanya, R., S700 (3P) S775 (144P) Parra-Palau, J.L., S722 (50P) Portner, R., S722 (49MO) Navaro, A., S806 (198P) Pasello, G., S723 (51P), S763 (119P), Porzio, G., S761 (117P) Navarro, A., S722 (50P), S766 (126P), S779 (149P), S796 (181P) Postel-Vinay, S., S752 (100MO) S767 (127P) Pasricha, S., S717 (44P) Potaris, K., S704 (14P) Neal, J.W., S773 (141P) Passaro, A., S754 (104P) Potter, D., S731 (66P) Neophytou, C.M., S709 (25P) Pastor-Escartın,́ I., S805 (196P) Powell, C., S808 (203MO) Neves, M.C., S809 (206P) Patel, G., S810 (208P) Powell, R.L., S731 (67P) Ng, C.S., S730 (64MO) Patel, J., S786 (162P) Pozas Perez,́ J., S724 (52P), S752 (100MO), Ngocamus, M., S707 (22P) Pateras, I.S., S704 (14P) S814 (218P) Nguyen, E., S757 (109P) Pati, A., S720 (48MO) Prasad, K.T., S790 (168P) Nguyen, H., S714 (37P) Patil, C.R., S791 (170P) Prelaj, A., S769 (133P), S797 (184P) Nguyen, H.M., S714 (37P) Patil, P., S763 (120P) Prenzel, R., S743 (88P) Nicolardi, L., S713 (35P) Pat, K.E., S790 (169P) Preston, J., S788 (164P) Nicotra, C., S707 (22P) Patsea, E., S704 (14P) Pretelli, G., S763 (119P) Nigade, G., S763 (120P) Pavan, A., S723 (51P), S763 (119P) Price, G., S808 (203MO) Nigro, O., S761 (117P) Paz-Ares, L., S720 (48MO), S722 (50P), Prince, S.S., S700 (4P) Nikolova, Z., S722 (50P) S748 (97O), S750 (98O) Prisciandaro, E., S744 (89P) Novello, S., S754 (104P), S773 (140P) Pecci, F., S713 (35P) Prosch, H., S717 (44P) Nuvola, G., S759 (113P) Pedrola, A., S806 (198P) Proto, C., S769 (133P), S797 (184P) Nyman, J., S729 (63MO) Peedell, C., S808 (203MO) Provencio, M., S722 (50P), S740 (81P), Peiris, V., S712 (31P) S752 (100MO) O’Brien, M.E.R., S787 (163P), S795 (180P) Peng, L.Y., S793 (174P) Pruniau, V., S790 (169P) O’Byrne, K., S813 (216P) Peng, R-W., S706 (19P) Psyrri, A., S762 (118P) Ocak, S., S790 (169P) Peng, W., S779 (150P) Puchinskaya, M., S797 (183P) Occhipinti, M., S769 (133P), S797 (184P) Pensieri, V., S713 (35P) Puig, T., S700 (3P) O’Doherty, D., S811 (212P_PR) Pentheroudakis, G., S762 (118P) Puri, S., S717 (44P) O’Dwyer, R., S811 (212P_PR) Peretz, I., S738 (79MO) Putra, B.P., S715 (40P), S716 (41P) O’Hagan, K., S810 (209P_PR) Perol, M., S798 (186TiP) Putra, F.N., S715 (40P), S716 (41P) Ohana, D., S810 (208P) Perol,́ M., S757 (109P), S758 (110P) Okamoto, I., S748 (97O) Perrone, F., S701 (7P), S789 (167P) Qiang, H., S726 (56P), S771 (137P) Okamoto, T., S776 (145P) Peters, M., S729 (61MO) Qiao, R., S727 (59P) Oksen, D., S785 (160P) Peters, S., S745 (93TiP) Qiu, M., S702 (8P), S703 (11P), S711 (29MO) Olier, C., S808 (204P) Petrovic, M.D., S753 (103P) Quaini, F., S701 (7P) Olmedo Garcıa,́ M.E., S701 (6P), S724 (52P), Pfeiffer, B., S784 (158P), S784 (159P) Quantin, X., S757 (109P), S758 (110P), S765 (124P), S765 (125P), S814 (218P) Phillips, I., S733 (71P) S798 (186TiP) Olson, P., S751 (99O_PR) Piccirillo, M.C., S789 (167P) Quattrocchi, C.C., S717 (42P) Orejana Martın,́ I., S814 (218P) Pichon, E., S719 (47P), S738 (79MO) Quinn, H., S788 (164P) Ortega Granados, A.L., S752 (100MO) Piedra, A., S768 (131P) Ostoros, G., S718 (45P) Piera, N., S788 (165P) Rades, D., S727 (58P) O’Sullivan, B., S731 (67P) Pierre, C., S794 (179P) Radosavljevic, D., S705 (17P) Otto, G., S783 (157P) Pierson, R.F., S792 (173P) Ragone, A., S798 (185TiP) Oulkhouir, Y., S719 (47P) Pieters, T., S765 (123P), S790 (169P) Rahman, M., S712 (33P) Ou, S-H.I., S699 (1P), S751 (99O_PR) Pinato, D.J., S761 (117P) Raimondi, L., S755 (106P) Owonikoko, T.K., S720 (48MO) Pinna, G., S699 (2P) Rakshit, S., S707 (21P), S714 (38P) Oyen, C., S790 (169P) Pinterpe, G., S713 (35P) Ramchandran, K., S773 (141P) Pipalia, N., S809 (205P) Ramella, S., S717 (42P) Pacheco, J.M., S751 (99O_PR) Piperdi, B., S748 (97O), S755 (105P), Ramlau, R., S748 (97O) Padda, S.K., S773 (141P) S756 (108P) Rana, D., S744 (91P) Page, J., S745 (92P) Piqueras, M., S788 (165P) Raskin, J., S783 (157P) Page, S., S795 (180P) Pireddu, A., S699 (2P) Rauthan, A., S763 (120P) Paik, P., S783 (157P) Pires, M.R., S768 (130P) Ravi, N., S790 (168P) Paksoy, N., S782 (155P), S782 (156P) Pisano, C., S773 (140P) Razis, E., S762 (118P) Palomeras, S., S700 (3P) Piscuoglio, S., S705 (15P) Rea, F., S723 (51P) Pal, P., S801 (191TiP) Pizzutilo, P., S754 (104P) Reale, M.L., S754 (104P), S773 (140P) Palumbo, G., S789 (167P) Planchard, D., S707 (22P), S752 (100MO), Rebordão Pires, M., S768 (129P), S769 (132P) Panakis, N., S808 (203MO) S764 (121P), S798 (185TiP) Rebuzzi, S.E., S802 (192TiP) Panda, D., S767 (128P) Planck, M., S706 (18P), S729 (63MO) Reck, M., S737 (78MO), S750 (98O), Pan, Y., S727 (60TiP), S748 (96O) Plumas, J., S798 (186TiP) S762 (118P), S780 (153P) Paoli, J-B., S747 (95TiP) Polanyi,́ Z., S718 (45P) Redondo, P.V., S735 (75P) April 2021 Abstracts S821

Reeves, J.A., S786 (162P) Samantas, E., S762 (118P) Signorelli, D., S797 (184P) Reginelli, A., S733 (70P) Samaras, I., S704 (14P) Signori, A., S802 (192TiP) Reguart, N., S796 (182P) Sanchez Becerra, M.V., S808 (204P) Silva, D., S702 (9P), S712 (31P) Reinmuth, N., S742 (85P), S798 (186TiP) Sanchez Cabrero, D., S812 (213P) Silva, M., S793 (176P), S811 (211P) Remon, J., S707 (22P) Sanchez-Hernandez, A., S788 (165P) Silvey, M., S770 (135P), S775 (143P), Ren, D., S729 (62MO) Sanchez-Pé rez,́ T., S722 (50P) S775 (144P) Ren, S., S748 (96O) San Romań Gil, M., S724 (52P), S814 (218P) Simmaco, M., S769 (133P) Reyes, R., S796 (182P) Santini, M., S805 (196P) Simon, G., S758 (110P) Rice, M., S744 (91P) Santis, M., S734 (74P) Singh, A., S731 (67P) Richard, D., S813 (216P) Santo, B., S717 (42P) Singhal, M., S767 (128P) Richardet, E., S750 (98O) Santon,́ A., S701 (6P), S814 (218P) Singh, H., S715 (39P) Ricordel, C., S794 (179P) Santorelli, M., S757 (109P), S758 (110P) Singh, N., S790 (168P) Ridi, I., S712 (33P) Santoro, A., S722 (50P) Siva, S., S738 (79MO) Riely, G.J., S751 (99O_PR) Sanz Gomez,́ L., S724 (52P), S765 (125P), Skandarajah, T., S712 (31P) Rietschel, P., S760 (115P) S814 (218P) Sloane, H., S788 (164P) Righi, L., S773 (140P) Sarosi,́ V., S718 (45P) Smit, E., S783 (157P) Rigney, M., S810 (209P_PR) Sasaki, T., S770 (134P) Soares, M.A.S., S735 (75P) Rıos-Hoyo,́ A., S724 (53P) Sathyanarayan, P., S788 (164P) Solanki, A., S731 (67P) Riudavets, M., S707 (22P), S768 (131P) Sato, Y., S776 (145P) Soliman, S., S813 (217P) Robinson, A.G., S748 (97O) Sawadogo, K., S765 (123P) Solomon, B., S738 (79MO), S786 (162P) Robles, T., S808 (204P) Sawhney, P., S810 (208P) Song, B-B., S786 (161P) Rodrigues Sousa, S., S734 (74P) Sawyer, W., S737 (78MO), S738 (79MO), Song, Q.Z., S729 (62MO) Rodriguez Abreu, D., S740 (81P) S747 (95TiP) Song, X., S781 (154P) Rodrıguez-Cid,́ J., S748 (97O) Scartozzi, M., S699 (2P) Song, Y., S786 (161P) Roeper, J., S710 (28P), S741 (83P), S743 (88P), Scattolin, D., S779 (149P) Soria, J-C., S752 (100MO) S772 (139P) Schaffer, M., S699 (1P) Sotelo, V., S808 (204P) Rogalla, P., S801 (191TiP) Schenker, M., S750 (98O) Soto Castillo, J.J., S701 (6P), S724 (52P), Rokszin, G., S718 (45P) Scherpereel, A., S750 (98O) S765 (124P), S765 (125P), S814 (218P) Roma, L., S705 (15P) Scherz, A., S783 (157P) Soto Parra, H., S748 (97O) Rosas Alonso, R., S709 (26P) Schettino, C., S789 (167P) Soulaymani, A., S713 (34P) Rose, J., S699 (1P) Schmid, R.A., S706 (19P) Sousa, G., S743 (87P), S768 (129P), Rosell, R., S752 (100MO) Schneider, M., S725 (54P) S768 (130P), S769 (132P) Rosen, L., S786 (162P) Schnöller, L., S726 (57P) Souto Moura, M., S806 (200P) Rosero Rodrıguez,́ D.I., S724 (52P), Schoenfeld, A., S799 (187TiP) Spaggiari, L., S744 (89P) S814 (218P) Schott, R., S758 (110P) Spagnuolo, A., S789 (167P) Rossi, G., S802 (192TiP) Schrauwen, W., S791 (171P) Spanu, D., S699 (2P) Rosso, E., S802 (192TiP) Schrobback, K., S813 (216P) Sparano, F., S805 (196P) Rothschild, S.I., S700 (4P) Schroeder, A., S753 (103P) Spasic, J., S705 (17P) Rouleau, E., S707 (22P) Schulz, C., S780 (153P), S800 (189TiP) Spigel, D.R., S745 (93TiP) Rounis, K., S705 (16P) Schwarzenberger, P., S748 (97O) Spiliotaki, M., S709 (25P) Rovira, A., S724 (53P) Scott, S., S787 (163P) Spinelli, G.P., S755 (106P) Rudolph, M., S786 (162P) Scriba, D., S743 (88P) Spira, A., S751 (99O_PR) Rühle, A., S742 (85P) Sebastian, M., S740 (82P), S743 (88P), Staaf, J., S706 (18P) Ruiz-Martınez,́ S., S700 (3P) S798 (186TiP) Stadhouders, R., S708 (24P) Ruiz, V., S788 (165P) Sedda, G., S744 (89P) Stanic, N., S705 (17P) Rupasinghe, T., S712 (31P) Seeva, P., S731 (67P) Stati, V., S754 (104P) Russo, A., S761 (117P) Senghas, K., S762 (118P) Stefani, A., S754 (104P) Rybkin, I., S751 (99O_PR) Serra, J., S768 (131P) Steinbusch, L., S738 (79MO) Ryder, A., S785 (160P) Serrano-Fernandez, M.J., S735 (76P) Steinestel, K., S740 (82P) Ryu, J.S., S760 (115P) Shan, L., S781 (154P) Steins, M., S725 (54P) Ryzhov, A., S734 (73P) Shan, X., S803 (195P) Stenzinger, A., S725 (54P), S762 (118P), Sharat Chandra, G., S767 (128P) S772 (139P), S780 (153P) Saba, G., S699 (2P) Sharma, A., S767 (128P) Stilwell, C., S808 (203MO) Sabari, J.K., S751 (99O_PR) Sharma, M., S715 (39P) Stockley, T., S736 (77TiP), S801 (191TiP) Sable, B., S720 (48MO) Sharma, S., S701 (5P) Stojanovic, G., S753 (103P) Saetzler, R., S739 (80P), S740 (82P) Shelton, D., S744 (91P) Stone, E., S733 (72P) Safi, M., S803 (195P) Shetty, A., S720 (48MO) Storey, C., S812 (214P) Saganelidze, K., S717 (43P) Shi, C., S789 (166P) Sträter, J., S739 (80P) Saggese, M., S798 (185TiP) Shih, J-Y., S761 (116P), S776 (145P), Stroh, C., S785 (160P) Saikia, J., S708 (23P) S777 (146P) Struikmans, H., S711 (30P) Saip, P., S782 (155P), S782 (156P) Shi, J., S753 (102P) Subramaniam, S., S794 (178P) Saith, S., S795 (180P) Shi, M., S779 (150P) Subramanian, J., S770 (135P), S775 (143P), Sakai, H., S750 (98O), S783 (157P) Shim, B.Y., S760 (115P) S775 (144P) Sala Gonzalez, M.A., S752 (100MO) Sibille, A., S790 (169P), S798 (186TiP) Suciningtias, M., S742 (86P), S809 (207P) Saleiro, S., S806 (200P) Sidorenkov, G., S714 (36P) Su, C-Y., S761 (116P) Salgueiro, F.R., S768 (130P), S769 (132P) Sierra-Rodero, B., S740 (81P) Sukari, A., S799 (187TiP), S800 (188TiP) Salomonsson, A., S706 (18P) Siesling, S., S711 (30P) Sullivan, I.G., S768 (131P) S822 Journal of Thoracic Oncology Vol. 16 No. 4S

Summers, Y., S760 (115P) Trunova, N., S737 (78MO) Wang, G., S793 (174P) Sundberg, J., S725 (55P) Tsantoulis, P., S772 (138P) Wang, G-S., S786 (161P) Sun, J-M., S803 (193P) Tsuboi, M., S745 (93TiP) Wang, H., S786 (161P) Sun, P., S731 (66P) Tufman, A., S741 (84P), S742 (85P), Wang, J., S711 (29MO), S727 (60TiP) Sun, X., S803 (195P) S780 (153P) Wang, K., S778 (147P) Suraweera, A., S813 (216P) Türk, A., S739 (80P), S740 (82P) Wang, L., S748 (96O), S778 (147P), Surmont, V., S791 (171P) S779 (150P) Suryavanshi, M., S701 (5P) Ulmer, M., S740 (82P) Wang, L-P., S786 (161P) Susanto, B., S759 (112P), S759 (114P), Umeyama, Y., S794 (177P) Wang, Q., S748 (96O), S786 (161P) S778 (148P), S779 (151P), S792 (172P) Urban,́ L., S718 (45P) Wang, R., S746 (94TiP), S748 (96O) Suyama, T., S794 (177P) Wang, W., S789 (166P) Swanton, C., S745 (93TiP) Vahlas, K., S704 (14P) Wang, W-X., S786 (161P) Syrigos, K., S762 (118P) Valame, S., S767 (128P) Wang, Y., S758 (111P), S781 (154P) Szalai, Z., S753 (103P) Valente, M.J., S806 (200P) Wang, Y.Y., S729 (62MO) Szima, B., S753 (103P) Valente, M.L.S.B., S806 (200P) Wang, Z., S753 (102P) Valerio,́ M.P., S734 (74P) Wehler, B., S800 (189TiP) Tabbo,̀ F., S773 (140P) Vamvakaris, I., S704 (14P) Wehler, T., S800 (189TiP) Tafreshi, A., S748 (97O) Van den Heuvel, M., S738 (79MO) Wermke, M., S780 (153P) Tagliamento, M., S802 (192TiP) Van der Sangen, M., S711 (30P) Westeel, V., S719 (47P) Takemoto, S., S794 (177P) Van Der Weijst, L., S791 (171P) White, M., S773 (141P) Tamasi,́ L., S718 (45P) Van Rossum, P., S729 (61MO) Wicks, K., S808 (203MO) Tancherla, A., S742 (86P), S759 (112P), Vansteenkiste, J.F., S790 (169P), Wierzbinska, J., S786 (162P) S759 (114P), S774 (142P), S778 (148P), S798 (186TiP) Wijesekera, S., S712 (31P) S779 (151P), S792 (172P) Van Wezel, T., S771 (136P) Wijovi, F., S742 (86P), S759 (112P), Tandiono, J., S759 (112P), S759 (114P), Vasquez,́ C.A., S700 (3P) S759 (114P), S774 (142P), S778 (148P), S778 (148P), S779 (151P), S792 (172P) Vasquez Osorio, E., S722 (49MO) S779 (151P), S792 (172P) Tan, D.S.W., S786 (162P) Vasseur, D., S707 (22P), S764 (121P) Wikström, A., S729 (63MO) Tandy, F., S742 (86P), S809 (207P) Vastag, A., S718 (45P) Willborn, K., S741 (83P), S743 (88P) Tang, K., S727 (60TiP) Vatansever, S., S782 (155P), S782 (156P) Winter, H., S725 (54P) Tang, M., S813 (216P) Veenhof, A., S703 (10P) Witte, H., S739 (80P), S740 (82P) Taniere, P., S731 (67P) Veillon, R., S783 (157P) Wong, Y.N.S., S810 (208P) Targato, G., S779 (149P) Velastegui, K., S751 (99O_PR) Wood, J., S733 (71P) Taugner, J., S726 (57P), S741 (84P), Velcheti, V., S755 (105P) Wood, V., S808 (203MO) S742 (85P) Vercauter, P., S738 (79MO) Wu, R., S793 (174P) Taus, Á., S724 (53P) Verhoeff, J.J.C., S729 (61MO) Wu, S., S788 (164P) Tavares, A., S702 (9P) Vicente Baz, D., S753 (103P) Wu, S-G., S761 (116P), S777 (146P) Taylor, A., S730 (65P), S731 (66P), Vicente, D., S748 (97O) S770 (135P), S775 (143P), S775 (144P) Vicidomini, G., S805 (196P) Xia, J., S753 (102P) Tehenes, S., S753 (103P) Vida Navas, E.M., S701 (6P), S724 (52P), Xia, L., S778 (147P) Teixeira, A.R., S809 (206P) S765 (124P), S765 (125P), S814 (218P) Xing, P., S781 (154P) Teixido, C., S796 (182P) Vieira, C., S809 (206P) Xu, B., S704 (13P) Teng, B., S744 (91P) Vilaça, M., S702 (9P) Xu, C., S786 (161P) Terhaard, C., S711 (30P) Viñolas, N., S740 (81P), S796 (182P) Xu, J., S727 (59P), S752 (101MO) Texier, M., S752 (100MO) Vioix, H., S784 (158P), S784 (159P) Xu, S., S729 (62MO) Thiberville, L., S719 (47P) Viscardi, G., S797 (184P), S805 (196P) Xu, X., S748 (96O) Thillays, F., S719 (47P) Vita, E., S754 (104P) Xu, Y., S760 (115P) Thippu Jayaprakash, K., S808 (203MO), Viteri, S., S699 (1P), S752 (100MO), S809 (205P) S783 (157P) Yadav, B., S800 (188TiP) Thomas, C.A., S760 (115P) Vitorino, M., S793 (176P), S811 (211P) Yamaguchi, H., S794 (177P) Thomas, M., S725 (54P), S762 (118P), Vladimirov, V., S748 (97O) Yan, F., S779 (150P) S772 (139P), S780 (153P), S783 (157P) Vlahiotis, A., S785 (160P) Yang, J.C-H., S798 (185TiP) Thomas, P.A., S719 (47P) Vliegenthart, R., S714 (36P) Yang, T-Y., S776 (145P) Thomas, S.S., S799 (187TiP) Vogazianos, P., S709 (25P) Yang, Z., S706 (19P), S748 (96O), Tianqing, C., S771 (137P) Voko,́ Z., S718 (45P) S758 (111P) Tiseo, M., S701 (7P), S802 (192TiP) von der Thüsen, J., S771 (136P) Yao, W., S727 (60TiP), S748 (96O) Tognazzo, S., S796 (181P) Voutsina, A., S704 (14P) Yashas, N., S763 (120P) Tolu, S., S699 (2P) Vroman, H., S708 (24P) Ye, F., S727 (60TiP) Tomas,́ T., S793 (176P), S811 (211P) Vundemodalu, P., S763 (120P) Ye, Z., S714 (36P) Topsch, J., S800 (189TiP) Yi, J., S753 (102P) Torchia, A., S796 (181P) Waddell, T., S736 (77TiP), S801 (191TiP) Yksnøy, Ø., S729 (63MO) Torniai, M., S761 (117P) Wagner, J., S741 (83P) Yoshimura, N., S770 (134P) Torres Jimenez,́ J., S701 (6P), S724 (52P), Wakelee, H., S764 (121P), S773 (141P) Yousaf, N., S787 (163P), S795 (180P) S765 (124P), S814 (218P) Walker, M., S785 (160P) Yu, G-H., S786 (161P) Torres, L., S764 (122P) Walther, J., S745 (92P) Yu, L., S727 (59P) Toufektzian, L., S704 (14P) Wang, C., S746 (94TiP) Yuqiong, L., S726 (56P) Trapani, D., S803 (195P) Wang, C-C., S761 (116P), S777 (146P) Yu, S., S779 (150P) Trigo, J.M., S722 (50P) Wang, D., S786 (161P) Yu, Y., S727 (60TiP), S778 (147P) April 2021 Abstracts S823

Zahra, O.S., S718 (46P) Zhang, Y., S720 (48MO), S748 (96O), Zhou, J., S753 (102P), S778 (147P) Zanaletti, N., S805 (196P) S778 (147P) Zhou, S., S808 (203MO) Zang, A., S727 (60TiP) Zhang, Y.L., S793 (174P) Zhou, Z., S711 (29MO) Zattarin, E., S769 (133P), S797 (184P) Zhan-Zhou, E., S808 (204P) Zhuang, W., S786 (161P) Zecca, E., S797 (184P) Zhao, K., S704 (13P) Zhu, H., S704 (13P) Zellweger, N., S700 (4P) Zhong, H., S727 (59P), S752 (101MO), Zhu, S., S729 (62MO) Zhang, B., S729 (62MO), S758 (111P) S789 (166P) Zhu, Y-C., S786 (161P) Zhang, C., S778 (147P), S781 (154P) Zhong, R., S727 (59P), S752 (101MO), Zielli, T., S701 (7P) Zhang, W., S748 (96O), S758 (111P), S789 (166P) Zou, Z., S781 (154P) S789 (166P) Zhou, C., S748 (96O) Zulato, E., S723 (51P) Zhang, X., S789 (166P) Zhou, D., S753 (103P) Zurawski, B., S750 (98O)