Study
| Open-label, randomized, phase 3 trial (BREAKWATER) |
| Untreated BRAF V600E–mutated metastatic colorectal cancer |
| Encorafenib + cetuximab + mFOLFOX6 vs. investigator’s choice of chemotherapy ± bevacizumab |
Efficacy
| ORR: 65.7% vs. 37.4% (encorafenib + cetuximab + FOLFOX vs. physician’s choice + bev) |
| mDoR: 13.9 mos vs. 10.8 mos |
| mPFS: 12.8 mos vs. 7.1 mos (HR: 0.53 [0.41–0.68]) |
| mOS: 30.3 mos vs. 15.1 mos (HR: 0.49 [0.38–0.63]) |
| 12-mo OS: 80.1% vs. 66.0% |
| 24-mo OS: 52.0% vs. 29.0% |
Safety
| Grade ≥3 AEs: 81.5% vs. 66.8% |
| Grade 5 AEs: 4.3% vs. 4.4% |
| AEs leading to treatment discontinuation: 26.7% vs. 17.5% |
| Dose reduction of any intervention: 65.5% vs. 54.1% |
N Engl J Med 2025;392:2104-17
Elez E,Yoshino T,Shen L Encorafenib, Cetuximab, and mFOLFOX6 in BRAF-Mutated Colorectal Cancer
http://doi.org/10.1056/NEJMoa2501912
Reviewed by Ulas D. Bayraktar, MD on Jun 2, 2025
