European expert panel consensus on the clinical management of BRAF V600E -mutant metastatic colorectal cancer.

Metastatic colorectal cancer (mCRC) is a heterogenous disease caused by various genetic alterations. The BRAF ^V600E mutation occurs in approximately 8-12% of patients and is characterised by an aggressive clinical course and poor prognosis. Here we review the current knowledge on BRAF ^V600E -mutant mCRC and provide a series of consensus statements on its clinical management. The treatment landscape for BRAF ^V600E -mutant mCRC has changed greatly due to the emergence of molecular targeted therapies (including BRAF inhibitors) and immune checkpoint inhibitors. A scientific literature search identified available data on molecular testing, treatments, and clinical monitoring of patients with BRAF ^V600E -mutant mCRC. Consensus statements were discussed and developed by a European expert panel. This manuscript provides consensus management guidance for different clinical presentations of BRAF ^V600E -mutant mCRC and makes recommendations regarding treatment sequencing choices. To guide appropriate clinical management and treatment decisions for mCRC patients, tumour tissue analysis for DNA mismatch repair/microsatellite status and, at a minimum, KRAS, NRAS, and BRAF mutational status is mandatory at the time of diagnosis. Finally, we discuss the rapidly evolving treatment landscape for BRAF ^V600E -mutant mCRC and define priorities for the development of novel therapeutic strategies that are needed to improve patient outcomes.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Andres Cervantes: Institutional research funding from Genentech, Merck Serono, Bristol Myers Squibb, Merck Sharp & Dohme, Roche, Beigene, Bayer, Servier, Lilly, Novartis, Takeda, Astellas, Takeda, and Fibrogen; and advisory board or speaker fees from Amgen, Merck Serono, Roche, Bayer, Servier, and Pierre Fabre in the last 5 years. Dirk Arnold: Participation in advisory boards and as invited speaker for AbbVie, ACE Oncology, Amgen, Aptitude Health, AstraZeneca, Boston Scientific, Bristol Myers Squibb, CRA International, Imedex, Ipsen, Ketchum, Merck, OncoLytics, Pierre Fabre, Roche, Samsung Bioepsis, Sanofi and Servier. Eric Van Cutsem: Participation to advisory boards for Abbvie, ALX, Amgen, Array, Astellas, Astrazeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KgaA, Mirati, Novartis, Nordic, Pierre Fabre, Pfizer, Roche, Seattle Genetics, Servier, Takeda, Terumo, Taiho, and Zymeworks; research grants from Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Ipsen, Lilly, Merck Sharp & Dohme, Merck KgaA, Novartis, Roche, and Servier paid to his institution. Erika Martinelli: Honoraria or consultation fees for speaker, consultancy or advisory roles, travel grant for congress participation from Amgen, AstraZeneca, Bayer, Eisai, Incyte, Merck Serono, Pierre Fabre, Roche, Servier, and ESMO. Fortunato Ciardiello: Advisory board member for Amgen, Roche, Merck KgaA, Pfizer, Bayer, Servier, MSD, Pierre Fabre, and Eisai. Harpreet Wasan: Consultant or advisory role: Servier, Pierre Fabre, Incyte, Bayer, Pfizer, Zymeworks, Merck KgaA Roche/Genentech/FM, Amgen, SIRTEX Medical, Erytech Pharma, BMS (Celgene), BTG, and UK NICE/BSI; clinical expert: Bayer, Pierre Fabre, ONCOSIL, Incyte, and Celgene; educational collaboration: Imedex/HMP, Medscape Education, and PeerView Institute for Medical Education and Physicians Education Resource (PER). Josep Tabernero: Consultant or advisory role: scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna Inc, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Scandion Oncology, Scorpion Therapeutics, Seattle Genetics, Servier, Sotio Biotech, Taiho, Tessa Therapeutics, and TheraMyc; stock ownership: Oniria Therapeutics; other: educational collaboration with Imedex/HMP, Medscape Education, MJH Life Sciences, and PeerView Institute for Medical Education and Physicians Education Resource (PER). Julien Taieb: Consultant or advisory role: scientific consultancy role for AMGEN, Astellas, AstraZeneca, BMS, F. Hoffmann-La Roche Ltd, Merck Serono, MSD, Novartis, Pfizer, Pierre Fabre, and Servier. Sebastian Stintzing: Consultant or advisory role for Amgen, Astra Zeneca, Bayer, Bayer, BMS, ESAI, Isofol, Lilly, Merck KgaA, MSD, Pierre-Fabre, Roche, Sanofi, Servier, Taiho, and Takeda; honoraria for talks from AMGEN, Astra-Zeneca, Bayer, BMS, ESAI, Isofol, Leo Pharma GmbH, Lilly, Merck KgaA, MSD, Pierre-Fabre, Roche, Sanofi, Servier, Taiho, and Takeda; institutional research funding from Merck KgaA, Pierre-Fabre, Servier, and Roche; other/educational collaborations with Medscape Foundation, COR2ED.’.
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