Effect of prior bevacizumab treatment in BRAF V600E-mutant metastatic colorectal cancer: Overall survival with encorafenib + cetuximab +/- binimetinib in BEACON CRC

Background Approximately 10% of patients with metastatic colorectal cancer (mCRC) have BRAF mutations, predominantly V600E. Encorafenib has been approved in combination with cetuximab in the US and the EU, and in combination with cetuximab with or without binimetinib in Japan, for the treatment of BRAF V600E-mutant mCRC after prior systemic therapy based on results from the BEACON CRC trial. The trial evaluated encorafenib plus cetuximab with or without binimetinib (triplet or doublet, respectively) versus investigators’ choice of irinotecan or FOLFIRI plus cetuximab (control). 1 First-line treatment options for patients with BRAF V600E-mutant mCRC include cytotoxic chemotherapy combined with inhibitors of VEGF or immune checkpoint inhibitors in patients with MSI-H tumors. The impact of sequential treatment with anti-VEGF and anti-EGFR therapies in mCRC has been the subject of investigation in recent years. Methods This post hoc analysis evaluated overall survival (OS) by prior bevacizumab treatment in patients with BRAF V600E-mutant mCRC treated with the triplet, doublet, or control regimens in the BEACON CRC study. Results Of 665 patients enrolled in the study, the number of patients in the triplet, doublet, and control arms who received prior bevacizumab were 136 (61%), 140 (64%), and 122 (55%), respectively. For patients in the triplet arm, median OS (95% confidence interval [CI]) for those who had no prior bevacizumab treatment, bevacizumab treatment < 4 months before study treatment, or bevacizumab treatment ≥ 4 months before study treatment was 12.6 months (9.3–17.8; n = 88), 8.1 months (7.2–9.6; n = 103), and 7.9 months (6.3–not reached; n = 33), respectively. In the doublet arm, median OS (95% CI) for the same categories was 9.4 months (7.6–16.5; n = 80), 8.3 months (6.2–11.2; n = 111), and 10.7 months (7.5–17.7; n = 29), respectively. In the control arm, median OS (95% CI) for the same categories was 7.4 months (5.6–9.5; n = 99), 5.1 months (4.0–6.4; n = 103), and 4.4 months (2.0–11.6; n = 19), respectively. Median OS using a 6-month prior bevacizumab cut-off was similar to that for the 4-month cut-off. Additional analyses exploring the potential impact of prior bevacizumab use on encorafenib plus cetuximab with or without binimetinib treatment will be presented. Conclusions This exploratory post hoc analysis evaluates OS in patients from BEACON CRC treated with encorafenib plus cetuximab with or without binimetinib to investigate the potential effects of prior bevacizumab treatment on subsequent regimens for patients with BRAF V600E-mutant mCRC. Reference: 1. Tabernero J, et al. J Clin Oncol. 2021;39(4):273–284. Clinical trial identification NCT02928224. Editorial acknowledgement Writing support provided by Jennifer Shepphird (Caudex), funded by Pfizer. Legal entity responsible for the study Pfizer. Funding Sponsored by Array Biopharma, in collaboration with Merck, ONO Pharmaceutical, and Pierre Fabre. Array Biopharma was acquired by Pfizer in July 2019. Disclosure S. Kopetz: Advisory / Consultancy: Roche, Redx Pharma, Jacobio, Merck, Navire Pharma, Holy Stone, Biocartis, Natera, Karyopharm Therapeutics, Repare Therapeutics, Genentech, Lilly, AstraZeneca/MedImmune, EMD Serono, Daiichi Sankyo, Amal Therapeutics, Boehringer Ingelheim, Bayer Health, Lutris, Pfizer, Amgen, Pierre Fabre, Symphogen, Novartis, Boston Biomedical, Ipsen, HalioDx. E. Van Cutsem: Advisory / Consultancy: Array, Astellas, Astrazeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Daiichi, Halozyme, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Pierre Fabre, Roche, Servier, Sirtex, Taiho; Research grant / Funding (institution): Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier. R. Yaeger: Advisory / Consultancy: Natera; Research grant / Funding (institution): Pfizer, Mirati Therapeutics, Boehringer Ingelheim. H. Wasan: Honoraria (self): Servier, Incyte, Pierre Farbre; Advisory / Consultancy: Servier, Incyte, Pierre Farbre; Speaker Bureau / Expert testimony: Servier, Incyte, Pierre Farbre; Research grant / Funding (institution): Pfizer, Sirtex; Travel / Accommodation / Expenses: Servier, Incyte, Pierre Farbre. T. Yoshino: Honoraria (self): Bayer, Chugai, Taiho, Eli Lilly, Merck Biopharma; Research grant / Funding (institution): Daiichi Sankyo, MSD, Ono, Parexel International, Taiho, Amgen. J. Desai: Honoraria (Institution): Pierre Fabre, Amgen; Research grant / Funding (institution): Roche/Genentech, Pfizer, Amgen, BMS, GSK, Novartis. A. Golden: Shareholder / Stockholder / Stock options: Pfizer Inc. M. Edwards: Full / Part-time employment: Pfizer. J. Tabernero: Honoraria (self): educational collaboration with Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER); Advisory / Consultancy: Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics and TheraMyc. All other authors have declared no conflicts of interest.