© Springer-Verlag 2015 SpringerMedizin.at/memo_inoncology SpringerMedizin.at 2/15 /memo_inoncology memo – inOncology SPECIAL ISSUE Congress Report ECC 2015 A GLOBAL CONGRESS DIGEST ON NSCLC Report from the 18th ECCO- 40th ESMO European Cancer Congress, Vienna 25th–29th September 2015 Editorial Board: Alex A. Adjei, MD, PhD, FACP, Roswell Park, Cancer Institute, New York, USA Wolfgang Hilbe, MD, Departement of Oncology, Hematology and Palliative Care, Wilhelminenspital, Vienna, Austria Massimo Di Maio, MD, National Institute of Tumor Research and Th erapy, Foundation G. Pascale, Napoli, Italy Barbara Melosky, MD, FRCPC, University of British Columbia and British Columbia Cancer Agency, Vancouver, Canada Robert Pirker, MD, Medical University of Vienna, Vienna, Austria Yu Shyr, PhD, Department of Biostatistics, Biomedical Informatics, Cancer Biology, and Health Policy, Nashville, TN, USA Yi-Long Wu, MD, FACS, Guangdong Lung Cancer Institute, Guangzhou, PR China Riyaz Shah, PhD, FRCP, Kent Oncology Centre, Maidstone Hospital, Maidstone, UK Filippo de Marinis, MD, PhD, Director of the Th oracic Oncology Division at the European Institute of Oncology (IEO), Milan, Italy Supported by Boehringer Ingelheim in the form of an unrestricted grant IMPRESSUM/PUBLISHER Medieninhaber und Verleger: Springer-Verlag GmbH, Professional Media, Prinz-Eugen-Straße 8–10, 1040 Wien, Austria, Tel.: 01/330 24 15-0, Fax: 01/330 24 26-260, Internet: www.springer.at, www.SpringerMedizin.at. Eigentümer und Copyright: © 2015 Springer-Verlag/Wien. Springer ist Teil von Springer Science + Business Media, springer.at. Leitung Professional Media: Dr. Alois Sillaber. Fachredaktion Medizin: Dr. Judith Moser. Corporate Publishing: Elise Haidenthaller. Layout: Katharina Bruckner. Erscheinungsort: Wien. Verlagsort: Wien. Herstellungsort: Linz. Druck: Friedrich VDV, Vereinigte Druckereien- und Verlags-GmbH & CO KG, 4020 Linz; Die Herausgeber der memo, magazine of european medical oncology, übernehmen keine Verantwortung für diese Beilage. Lecture Board for this issue: Maximilian Hochmair, MD; Helmut Prosch, MD; Martin Filipits, MD The Publisher does not assume any legal liability or responsibility for the accuracy, completeness, or usefulness of the information supplied herein, nor for any opinion expressed. The Publisher, its agent, and employees will not be liable for any loss or damage arising directly or indirectly from possession, publication, use of, or reliance on information obtained from this report. It is provided in good faith without express of implied warranty. Reference to any specific commercial product or service does not imply endorsement or recommendation by the Publisher. All articles are peer-reviewed and protected from any commercial influence. This issue is intended only for healthcare professionals outside the US, the UK, Australia and Canada. ECC2015 special issue Table of Contents 2 Preface 3 News on targeted agents in the advanced setting 6 Interview: “Liquid biopsy is a revolution” 7 Pivotal results and sub-analyses in the field of immunotherapy 10 Interview: “Immunotherapy has opened up a new avenue of research” 11 Lung cancer screening: diagnosis in the nick of time 12 Genomic testing – becoming part of everyday practice 13 Optimising treatment in local and regional lung cancer 14 Small-cell lung cancer: established and novel approaches © vladi79 / iStock other important endpoints, such as Preface quality of life, and define the benefits of new drugs in difficult-to-treat sub- groups. Refined molecular testing tech- Dear Colleagues, niques have become available, although their wide-spread implementation in Oncologists are currently witnessing clinical practice has yet to be improved. rapid diagnostic and therapeutic ad- Significant therapeutic advances vances in their field. These advances were also shown for the immune check- require that physicians are up-to-date point inhibitors nivolumab and pem- regarding the ever-changing standards brolizumab, while new representatives of care. With the present publication, of this drug class, such as atezolizumab, we hope to contribute to this goal, by are well on their way. Nivolumab also summarising recent findings in the di- excelled in the treatment of patients agnosis and treatment of lung cancer, with small-cell lung cancer. However, therapy might be improved by use of as presented at the European Cancer the patient selection through predictive the IASL/ATS/ERS classification in the Congress (ECC) that took place in Vi- biomarkers still needs further research future. Finally, sublobar resection was enna, from 25th–29th September, 2015. with regard to these novel immunother- shown to be feasible in stage IA tu- Innovations for patients with ad- apeutics. mours according to HRCT and maxi- vanced non–small-cell lung cancer are Early-stage and locally advanced mum standardized uptake values on of particular interest due to their poor non–small-cell lung cancer deserves at- FDG-PET/CT. prognosis. Targeted agents have al- tention as well, in particular with regard ready been shown to improve survival to improving long-term outcomes. For outcomes in this setting. The latest patients with adenocarcinoma, the se- Robert Pirker, MD, Medical University analyses shed light on their effects on lection of patients for adjuvant chemo- of Vienna, Vienna, Austria 2 2/2015 © Springer-Verlag memo special issue ECC2015 News on targeted agents in the advanced setting Afatinib in squamous-cell 1,0 carcinoma: update of LUX- Afatinib Erlotinib Lung 8 Median, month 7.9 6.8 0,8 (95 % CI) (7.2–8.7) (5.9–7.8) Squamous-cell carcinoma of the lung HR (95 % CI) 0.81 (0.69–0.95) p value 0.0077 represents approximately 30 % of non– 0,6 small-cell lung cancer (NSCLC) cases. Until 2015, docetaxel and erlotinib were 36.4 % the only approved second-line treat- 0,4 22.0 % ment options in these patients. Typi- Estimated OS probability 28.2 % cally, squamous-cell carcinoma of the 0,2 lung has a high burden of somatic muta- 14.4 % tions and genomic alterations. Overex- 0,0 pression and dysregulation of EGFR, 0 3 6 9 12 15 18 21 24 27 30 FGFR1, PI3K and their downstream pathways are implicated in the patho- Time (months) genesis, providing a rationale for the use Figure 1: Overall survival with afatinib versus erlotinib in LUX-Lung 8 of ErbB inhibitors in this setting of ma- jor medical need. were identified. According to the bio- mean scores over time significantly fa- The global, open-label, randomised, marker analyses, the prevalence of voured afatinib over erlotinib for cough phase III LUX-Lung 8 trial compared the EGFR genomic aberrations was consist- (p = 0.0091), dyspnoea (p = 0.0024), irreversible ErbB family blocker afatinib ent with prior reports in patients with and pain (p = 0.0384). with the reversible EGFR tyrosine ki- squamous-cell carcinoma, and no pre- A diarrhoea substudy (n = 63) ana- nase inhibitor (TKI) erlotinib in a total dictive associations between genetic al- lysed the time course and severity of di- of 795 patients with squamous-cell car- terations and OS or PFS were observed. arrhoea using patient diaries at se- cinoma of the lung after failure of first- Assessment of EGFR immunohisto- lected centres. In this substudy, the line platinum-based chemotherapy. chemistry and blood-based markers is overall incidence of all-grade diarrhoea Compared to erlotinib, afatinib signifi- ongoing, as well as further bioinformat- was similar to that reported in the over- cantly improved progression-free sur- ics analysis of next-generation se- all trial population (86.1 % with afatinib, vival (PFS; median 2.4 vs. 1.9 months; quencing. 51. 8 % with erlotinib). Nineteen per- HR, 0.82, 95 % CI 0.68-1.00, p = 0.0427) cent (7 out of 36) of afatinib-treated pa- and overall survival (OS; median 7.9 vs. Quality of life and other tients reported grade ≥ 3 diarrhoea, 6.8 months; HR, 0.81, 95 % CI 0.69-0.95; outcomes with a mean duration of 3 days. No pa- p = 0.0077; Figure 1) [1]. The OS effect of tient discontinued study treatment due afatinib was consistent across sub- The outcome improvements obtained to this AE. groups. in LUX-Lung 8 were accompanied by Overall, these analyses confirm the At the ECC, the updated PFS results similar changes in patient-reported clinical relevance of the improvements and exploratory genetic analyses using outcomes [3]. Prespecified analyses us- observed for PFS, OS and tumour re- next-generation sequencing of select tu- ing the European Organisation for Re- sponse with afatinib in LUX-Lung 8. The mour samples were reported [2]. The PFS search and Treatment of Cancer (EO- researchers concluded that afatinib results significantly favoured afatinib RTC) core quality-of-life questionnaire should be considered the TKI of choice (2.6 vs. 1.9 months; HR, 0.81; p = 0.0103). (QLQ-C30) and its lung-cancer-specific for second-line treatment of squa- Furthermore, there was a significant im- module (QLQ-LC13) showed signifi- mous-cell carcinoma of the lung. provement in disease control rate (DCR; cantly higher proportions of patients 50.5 % vs. 39.5 %; p = 0.002). More pa- reporting improved global health sta- Assessment of nintedanib in tients in the afatinib group had an objec- tus/ quality of life and cough with squamous-cell carcinoma tive response (5.5 % vs. 2.8 %), and me- afatinib than with erlotinib. For dysp- dian duration of response was longer noea and pain, a non-significant ad- Nintedanib is an oral triple angiokinase than in the erlotinib arm (7.3 vs. 3.7 vantage of afatinib compared with erlo- inhibitor that targets factors of three ma- months). Adverse events (AEs) occurred tinib was observed. Afatinib jor proangiogenic pathways. Based on in both arms at similar rates, which also significantly delayed time to deteriora- the results of the randomised, placebo- applied to grade ≥ 3 AEs. tion (TTD) of dyspnoea compared to controlled, phase III LUME-Lung 1 study No biomarkers for the selection of erlotinib, and there was a trend towards [4], nintedanib has been approved in patients for treatment with afatinib delayed TTD of cough.