Encorafenib, Cetuximab, and mFOLFOX6 in BRAF-Mutated Colorectal Cancer
- Author(s)
- Elez, E; Yoshino, T; Shen, L; Lonardi, S; Van Cutsem, E; Eng, C; Kim, TW; Wasan, HS; Desai, J; Ciardiello, F; Yaeger, R; Maughan, TS; Morris, VK; Wu, C; Usari, T; Laliberte, R; Dychter, SS; Zhang, X; Tabernero, J; Kopetz, S; BREAKWATER Trial Investigators;
- Journal Title
- New England Journal of Medicine
- Publication Type
- Online publication before print
- Abstract
- BACKGROUND: First-line treatment with encorafenib plus cetuximab (EC) with or without chemotherapy (oxaliplatin, leucovorin, and fluorouracil [mFOLFOX6]) for BRAF V600E-mutated metastatic colorectal cancer, an aggressive subtype with a poor prognosis, was compared with standard care (chemotherapy with or without bevacizumab) in an open-label, phase 3 trial, which showed significance regarding one of the two primary end points, objective response according to blinded independent central review (odds ratio for EC+mFOLFOX6 vs. standard care, 2.44; one-sided P<0.001). This result led to accelerated Food and Drug Administration approval of this investigational combination therapy for BRAF V600E-mutated metastatic colorectal cancer, including as first-line therapy. Data on progression-free survival (the second primary end point) and an updated interim analysis of overall survival are now available. METHODS: We randomly assigned patients with untreated BRAF V600E-mutated metastatic colorectal cancer to receive EC, EC+mFOLFOX6, or standard care. The two primary end points were objective response (reported previously) and progression-free survival according to blinded independent central review in the EC+mFOLFOX6 group and the standard-care group. The key secondary end point was overall survival. RESULTS: Significantly longer progression-free survival was seen with EC+mFOLFOX6 than with standard care (median, 12.8 vs. 7.1 months; hazard ratio for progression or death, 0.53; 95% confidence interval [CI], 0.41 to 0.68; P<0.001). In an interim analysis, overall survival was significantly longer with EC+mFOLFOX6 than with standard care (median, 30.3 vs. 15.1 months; hazard ratio for death, 0.49; 95% CI, 0.38 to 0.63; P<0.001). The incidence of serious adverse events during treatment was 46.1% with EC+mFOLFOX6 and 38.9% with standard care. Safety profiles were consistent with those known for each agent. CONCLUSIONS: This trial showed significantly longer progression-free survival and overall survival with first-line treatment with EC+mFOLFOX6 than with standard care among patients with BRAF V600E-mutated metastatic colorectal cancer. (Funded by Pfizer and others; BREAKWATER ClinicalTrials.gov number, NCT04607421.).
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1056/NEJMoa2501912
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- Refer to copyright notice on published article.
Creation Date: 2025-06-03 07:20:22
Last Modified: 2025-06-03 07:20:41