REGIONAL WORKSHOP FINAL PROGRAMME

Grand Rounds metastatic colorectal cancer 21-22 December 2017- , GENERAL INFO GENERAL

GENERAL

2 INFORMATION3 Grand Rounds metastatic colorectal cancer

Overview CME Provider The development of new drugs and the interdisciplinary management of the disease have resulted EXCEMED is a non-profit foundation dedicated, since the last four decades, to the development in a meaningful increase in survival for patients with metastatic colorectal cancer. As the number of high-quality medical education programmes all over the world. EXCEMED adheres to of therapeutic options increases, insights into the biology of the disease and biomarker-driven the guidelines and standards of the European Accreditation Council for Continuing Medical therapeutic strategies are expected to improve patients survival and rationalize therapeutic Education (EACCME®) which states that continuing medical education must be balanced, approaches. Recent data reveals that right- and left-sided primary colorectal cancers are clinically independent, objective and scientifically rigorous. and biologically different. Tumor sidedness has significant prognostic and predictive value that will impact on the clinical management of metastatic colorectal cancer patients. Clinical research and medical care are closely related activities and the development of an integrated learning health care system will contribute to generating and applying clinically relevant medical knowledge producing benefits for present and future patients. Learning objectives By attending this educational regional workshop, participants will be able to: • analyse colorectal cancer biology and molecular biomarkers of clinical relevance • review biomarker-driven therapeutic strategies in patients with metastatic colorectal cancer • evaluate the essentials of continuum of care approach for patients with metastatic colorectal cancer within a multidisciplinary team setting Target audience This programme is intended for oncologists and practicing clinicians who have an interest in understanding colorectal cancer biology and building individual competencies in the management of the disease.

4 5 Venue This educational regional workshop takes place at the: Hilton Conrad Hotel Sheikh Zayed Road Dubai, United Arab Emirates

Language The official language of this educational regional workshop is English. FACULTY CME Provider EXCEMED - Excellence in Medical Education Programme Manager: Michela Fiuzzi T +39 06 420413 252 - F +39 06 420413 677 [email protected]

Medical Advisor: Cristina Raimondi [email protected]

For any logistic inquiry, please contact: Meridiano Congress International Event Manager: David Slangen T +39 06 88 595 250 - F +39 06 88595 234 [email protected]

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6 7 FACULTY Faculty

Hassan Jaafar Tawam Hospital , United Arab Emirates

Claus-Henning Köhne Department of Oncology and Hematology Klinikum Oldenburg Oldenburg, Germany

Alberto Sobrero Department of Medical Oncology IRCCS San Martino IST Genoa, Italy

Julien Taieb Department of Gastroenterology and Digestive Oncology Hôpital Européen Georges-Pompidou Assistance Publique-Hôpitaux de Paris (AP-HP) Paris Descartes University Paris, France

Sally Temraz AUBMC - American University of Beirut Medical Center PROGRAMME Beirut, Lebanon

Farahnaz Vafaie Zadeh Tehran University Medical School Teheran,

8 PROGRAMME9 Thursday, 21 December 2017 Friday, 22 December 2017

14.00 Welcome A. Sobrero (Italy)

Session I Molecular pathology and biomarkers Session II Treatment decisions in metastatic colorectal cancer (I)

Chairs: H. Jaafar (UAE), S. Temraz (Lebanon), F. Vafaie Zadeh (Iran) Chairs: H. Jaafar (UAE), S. Temraz (Lebanon), F. Vafaie Zadeh (Iran)

14.15 L1: Critical pathways in metastatic colorectal cancer (mCRC) 09.00 L5: RAS Wild-type and BRAF Wild-type mCRC A. Sobrero (Italy) A. Sobrero (Italy)

14.45 L2: Molecular biomarkers for mCRC 09.30 L6: Primary tumor location of RAS wild-type mCRC: left vs right A. Sobrero (Italy) C.H. Köhne (Germany)

15.15 Coffee break 10.00 WORKING GROUPS: Clinical cases discussion J. Taieb (France), A. Sobrero (Italy), C.H. Köhne (Germany) 15.30 L3: Evidence-based recommendations for molecular testing of mCRC C.H. Köhne (Germany) 10.30 Coffee break

10.45 L7: RAS mutated and BRAF mutated mCRC 16.00 ROUNDTABLE: Key guidelines questions J. Taieb (France) J. Taieb (France), A. Sobrero (Italy), C.H. Köhne (Germany)

11.15 ROUNDTABLE: Frontline Strategies for Metastatic Colorectal Cancer 16.30 L4: Tumor heterogeneity and blood-based biomarkers J. Taieb (France), A. Sobrero (Italy), C.H. Köhne (Germany) J. Taieb (France)

12.15 WORKING GROUPS: Clinical cases discussion 17.00 Closing remarks J. Taieb (France), A. Sobrero (Italy), C.H. Köhne (Germany)

17.15 End of the first day 13.00 Lunch

Legend

L: Lecture : Q&A : Roundtable :Working Groups

10 11 Friday, 22 December 2017

Session III Treatment decisions in metastatic colorectal cancer (II)

Chairs: H. Jaafar (UAE), S. Temraz (Lebanon), F. Vafaie Zadeh (Iran)

14.00 L8: Oligometastatic disease C.H. Köhne (Germany)

14.30 L9: Therapy after progression J. Taieb (France)

15.00 WORKING GROUPS: Clinical cases discussion J. Taieb (France), A. Sobrero (Italy), C.H. Köhne (Germany)

15.30 L10: Spotlight - Molecular classification of CRC C.H. Köhne (Germany)

15.45 L11: Spotlight - Immunotherapy for mCRC J. Taieb (France)

16.00 Concluding remarks

End of the workshop

Legend

L: Lecture : Q&A : Roundtable :Working Groups

12 13 Faculty disclosures

EXCEMED adheres to guidelines of the European Accreditation Council for Continuing Medical Education (EACCME®) and all other professional organizations, as applicable, which state that programmes awarding continuing education credits must be balanced, independent, objective and scientifically rigorous. Investigative and other uses for pharmaceutical agents, medical devices, and other products (other than those uses indicated in approved product labeling/package insert for the product) may be presented in the programme (which may reflect clinical experience, the professional literature or other clinical sources known to the presenter). We ask all presenters to provide participants with information about relationships with pharmaceutical or medical equipment companies that may have relevance to their lectures. This policy is not intended to exclude faculty who have relationships with such companies; it is only intended to inform participants of any potential conflicts so that participants may form their own judgements, based on full disclosure of the facts. Further, all opinions and recommendations presented during the programme and all programme-related materials neither imply an endorsement nor a recommendation on the part of EXCEMED. All presentations represent solely the independent views of the presenters/authors.

The following faculty have provided no information regarding significant relationship with commercial supporters and/or discussion of investigational or non-EMEA/FDA approved (off- label) uses of drugs as of 12 December 2017.

Hassan Jaafar Claus-Henning Köhne Alberto Sobrero Julien Taieb Sally Temraz Farahnaz Vafaie Zadeh BIOGRAPHIES

14 BIOGRAPHIES Hassan Jaafar Claus-Henning Köhne Tawam Hospital Department of Oncology and Hematology Abu Dhabi, United Arab Emirates Klinikum Oldenburg Oldenburg, Germany

Hassan Jaafar, is a medical consultant American society of clinical oncology) Claus-Henning Köhne studied medicine secretary. He is also a member of the in Tawam hospital (affiliated with Johns Member of the Scientific and Education at the Medical School Hannover in AIO Germany and the German Cancer Hopkins) UAE, He is being in tawam Committee of the Arab Collaborative Germany and at the University of Society. He serves as a consultant for since the year 2000 He received his Hematology and Oncology Group Glasgow in Scotland, specializing in the European Agency for Medicinal M. B. Ch. B (MD) in 1992, the internal (ACHOG). internal medicine, haematology and Products (EMA) and coordinated medicine board in 1997, and he passed oncology. He has since held senior several EORTC-trials as well as being a the Arab board exam in internal positions at the Robert-Rössle-Hospital Founding Member of the Pan-European medicine, he completed a 3 years of (Department of Haematology/Oncology Trials for ad-juvant colon Cancer fellowship in hematologyoncology and and Tumour Immunology), Humboldt- (PETACC). Prof. Köhne is a special certified as a medical hematologist University of Berlin (Charité), and at guest professor of the First Affiliated oncologist from American university the University Hospital Rostock, Clinic Hospital of Dalian Medical University/ hospital of Beirut in the year 2000. and Policlinic of Internal Medicine, and a visiting Professor of Dalian He is the author and coauthor of more Department of Haematology/Oncology. Medical University of the Second than 40 peer reviewed papers and Prior to his current positions he Affiliated Hospital/China, where he is abstracts. He is involved in more than was appointed Professor of Medical also a member of the Sino-German- 6 ongoing phase II and phase III trials Oncology at the Medical Clinic I, Cancer-Center Oldenburg/Dalian. He regional and international and he is University Carl-Gustav-Carus of the also organizes the ESMO Preceptorship a member of the GOG (gulf oncology Technical University Dresden. He is programme for colorectal cancer. group) which conduct 2 phase II trials in a member of the European Society Prof. Köhne is a reviewer of various the last 2 years He is a lecturer in AlAin for Medical Oncology (ESMO) and journals including the International university faculty of medicine He currently chairs the Oncology Pro Journal of Cancer, Oncology, Annals is member in many societies (UAE advisory group of ESMO, the American of Oncology (for which he is also a Oncology and radiation therapy Society of Clinical Oncology (ASCO) board member), Critical Reviews in association, Lebanese hematology and and the Gastrointestinal Tract Cancer Oncology/Haematology, Onkologie, oncology association, ESMO European Cooperative Group of the EORTC British Journal of Cancer and Journal society of medical oncology and ASCO (GITCCG), where he has served as of Clinical Oncology.

16 17 Alberto Sobrero Julien Taieb Department of Medical Oncology Department of Gastroenterology and Digestive Oncology IRCCS San Martino IST Hôpital Européen Georges-Pompidou Genoa, Italy Assistance Publique-Hôpitaux de Paris (AP-HP) Paris Descartes University Paris, France

Alberto Sobrero is the Head of the of ASCO (2007-2008), the Educational Julien Taieb is a gastroenterologist and has been Associate Editor of Medical Oncology Unit at Ospedale Committee of ESMO (2008-2014, specialised in GI oncology and the Clinics and Research in Hepatology San Martino in Genova, Italy. After his Chair of the GI committee 2012-2016) head of the gastroenterology and GI and Gastroenterology since 2010 and MD from the University of Genova, he and is the chairman of the ESMO oncology department of the Georges a regular reviewer for the Lancet took up the position of postdoctoral President Nominating Committee. He Pompidou European Hospital, Paris Oncology, Journal of Clinical Oncology, Associate in Medical Oncology at Yale has received the ESMO award in 2016 Descartes University. His research Annals of Oncology and the European University, Connecticut. After receiving and is the chairman of the scientific interests include colorectal cancer, Journal of Cancer. his medical degree from the University committee of the ESMO 2017 congress. hepatocellular carcinoma, gastric and Prof Taieb is the author of over 65 of Genova, Prof. Sobrero took up the His main research interests include pancreatic cancer, and the role of the recent publications and 41 abstracts position of postdoctoral Associate in gastrointestinal cancer treatment and immune response in cancer, and he published at recent meetings focussing Medical Oncology at Yale University, design and interpretation of clinical is leading currently as PI or co-PI 9 on his key research areas: colorectal USA. In 1983, he became Associate trials in oncology. phases II and III clinical trials in the cancer, gastric carcinoma, pancreatic Research Scientist in Medical Oncology field of GI oncology and responsible of cancer, and the role of the immune at Yale. Before returning to Genova a laboratory research team (INSERM response in cancer. in 1985, he completed a residency in U970 équipe 10). Internal Medicine at the Yale Affiliated He is a member of several medical Norwalk Hospital. societies, including different French From 2002 to 2006, Professor Sobrero gastroenterology and oncology has been the Chairman of the Protocol cooperative groups and societies Review Committee of the EORTC and (FFCD, GERCOR, SNFGE), the American has been part of the faculty of the Society of Clinical Oncology (ASCO), ASCO-FECS Clinical Research courses and the European Society for Medical at Flims for 7 years. He has served Oncology (ESMO). on the editorial board of the Journal Professor Taieb was Associate Editor of Clinical Oncology 2004-2006, has of Abstract Gastroenterology (2000- been part of the Scientific Committee 2003), of Cancerodigest since 2004

18 19 Sally Temraz Farahnaz Vafaie Zadeh AUBMC - American University of Beirut Medical Center Tehran University Medical School Beirut, Lebanon Teheran, Iran

Sally Temraz is an assistant professor Farahnaz Vafaie Zadeh received her of clinical medicine at the Naef MD from Tehran University of Medical Bassile Cancer Center of the American Sciences (TUMS) and she specialized in university of Beirut medical center. Hematology in 2006. After graduation, (AUBMC). Her main interest and she has continued her work as a research focus is in gastrointestinal consultant Hematologist -medical and genitourinary cancers. She has oncologist in Tehran Oil Hospital. published several articles in peer Currently she is an Assistant professor reviewed journals. in Tehran University Medical School. She is a consultant Hematologist -medical oncologist in Imam Khmeini hospital and Arash Women Hospital. Her main interest and research focus is in gastrointestinal cancers. Vafaie Zadeh has conducted several cancer research projects and published articles in local and international peer reviewed journals.

20 21 LECTURES 22 23 LECTURES Critical pathways in metastatic colorectal cancer (mCRC) Molecular biomarkers for mCRC

L1 A. Sobrero (Italy) L2 A. Sobrero (Italy)

Development of colorectal cancer occurs via a number of key pathways, with the Evidence supports mutational testing of specific genes in the EGFR signalling clinicopathological features of specific subgroups being driven by underlying pathway, since they provide clinically actionable information for targeted therapy molecular changes. of CRC with anti-EGFR monoclonal antibodies. • Colorectal Carcinogenesis • BRAF and MMR mutations as prognostic biomarkers • Microsatellite Instability • KRAS and NRAS as negative predictors of benefit to anti-EGFR therapies • Individual Somatic Mutations • MMR status as predictive biomarker (adjuvant therapy, anti-PD-1/PD-L1 therapy) • Molecular classifications (genomic classification, microenvironment classification, integrative • HER2 amplifications classification)

NOTES NOTES

24 25 Evidence-based recommendations for molecular testing of mCRC ROUNDTABLE: Key guidelines questions

L3 C.H. Köhne (Germany) J. Taieb (France), A. Sobrero (Italy), C.H. Köhne (Germany)

Molecular testing to select targeted and conventional therapies for patients with Key Guideline Questions (Sepulveda AR, et al. J Mol Diagn. 2017;(2):187-225). colorectal cancer (CRC) has been the focus of a number of recent studies and is • What biomarkers are useful to select patients with CRC for targeted and conventional becoming standard practice for management of patients with CRC. therapies? • Recommendations from international guidelines on CRC molecular testing (eg. • How should biomarker testing for CRC management be performed? NCCN, ESMO) • Are there emerging genes/biomarkers that should be routinely tested in CRC? • ASCP-CAP-AMP-ASCO evidence-based guidelines (2017) for molecular biomarker testing

NOTES NOTES

26 27 Tumor heterogeneity and blood-based biomarkers RAS Wild-type and BRAF Wild-type mCRC

L4 J. Taieb (France) L5 A. Sobrero (Italy)

The tumor biopsy depicts only a single timeframe from a single site and might be inadequate Patients who do not harbour activating mutations in RAS and BRAF derive the most benefit to characterize a tumor because of intratumoral and intermetastatic heterogeneity. from first-line combination treatment with chemotherapy and anti-EGFR therapy. The A great deal of interest has been raised recently for noninvasive prognostic and/or question of which biologic therapy is superior in the first line has been investigated in therapy-predictive molecular biomarkers. three large trials. • Tumor heterogeneity and tissue sampling bias • EGFR inhibitors in RAS wild-type disease • Longitudinal sampling strategies liquid biopsy • Head to head comparison (anti-EGFR/anti-angiogenic drugs): International trials FIRE3, • Clinical relevance of longitudinal monitoring of mCRC CALGB/SWOG 80405 and PEAK

NOTES NOTES

28 29 Primary tumor location of RAS wild-type mCRC: left vs right RAS mutated and BRAF mutated mCRC

L6 C.H. Köhne (Germany) L7 J. Taieb (France)

CRCs can be characterised by their primary tumour location within the colon. Differences in RAS and RAF are downstream effectors of EGFR-ligand activated signalling. Mutations the microbiome, clinical characteristics and chromosomal and molecular characteristics in RAS and RAF result in constitutive activation of downstream effectors, resulting in have been reported between the right and left side of the colon. the bypass of EGFR-driven signalling and resistance to anti-EGFR therapy. • Molecular characteristics of left and right-sided CRC • Doublet and triplet chemotherapy • Primary tumor sidedness as surrogate for tumor biology • Anti-angiogenic drugs in first line setting • Predictive effects of primary tumour location on clinical outcome • Targeting downstream effector pathways - biological and clinical insights for first and second line treatments

NOTES NOTES

30 31 ROUNDTABLE: Frontline Strategies for Metastatic Colorectal Cancer Oligometastatic disease J. Taieb (France), A. Sobrero (Italy), C.H. Köhne (Germany) L8 C.H. Köhne (Germany)

The plethora of available new agents and multidisciplinary management have improved Studies of selected patients with mCRC undergoing surgical resection of liver metastases the prognosis of metastatic colorectal cancer and have correspondingly made first- has shown that cure is possible with multidisciplinary management of oligometastatic line treatment decisions variable and complex. disease. Among the others: • Criteria for liver metastases resection • Fit vs unfit patients • Resectability criteria for surgical resection • Goals of Therapy • Potentially resectable metastases and conversion therapy • Drug combinations • Local therapies for metastases • Maintenance therapy

NOTES NOTES

32 33 Therapy after progression Spotlight - Molecular classification of CRC

L9 J. Taieb (France) L10 C.H. Köhne (Germany)

Following disease progression after the standard in both, 1st and 2nd line, combination • A 5-year-perspective on the different molecular classifications and their clinical and chemotherapy with monoclonal antibodies, many patients maintain a good performance therapeutical relevance. status and a significant proportion is motivated to undergo further therapy. Choices of treatment beyond the second line setting for mCRC are therefore becoming increasingly important. • Treatment goals and treatment options in second line and beyond • How to best integrate new treatment options • Treatment re-introduction and re-challenge strategies

NOTES NOTES

34 35 NOTES

Spotlight - Immunotherapy for mCRC

L11 J. Taieb (France)

• A 5-year-perspective on immunotherapy in mCRC, patient selection and novel combinations of immunotherapeutic agents

NOTES

36 37 NOTES NOTES

38 39 NOTES NOTES

40 41 All EXCEMED programmes are organized solely to promote the exchange and dissemination of scientific and medical information. No forms of promotional activities are permitted. There may be presentations discussing investigational uses of various products. These views are the responsibility of the named speakers, and do not represent an endorsement or recommendation on the part of EXCEMED. This programme is supported by independent educational grants received from Merck Serono Middle East FZ- LLC, Dubai, United Arab Emirates and Università Vita Salute San Raffaele, Milan, Italy.

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