New Reference: Encorafenib, Cetuximab, Chemotherapy in bRAF Mutant Colorectal Cancer

Study

Phase 3, multicenter, randomized trial (BREAKWATER)

Previously untreated BRAF V600E-mutant mCRC

encorafenib + cetuximab (EC) +mFOLFOX6 vs. SOC

Efficacy

ORR: 60.9% vs. 40.0% (EC+mFOLFOX6 vs. SOC) (OR: 2.443 [1.403-4.253])

mDoR: 13.9 mos vs. 11.1 mos

mOS: NE vs. 14.6 mos (HR: 0.47 [0.318-0.691])

6-mo OS: 92.3% vs. 87.1%

12-mo OS: 79.5% vs. 66.1%

Safety

Grade ≥3 AEs: Nausea (51.1% vs. 48.2%), anemia (36.4% vs. 22.8%), diarrhea (34.2% vs. 46.9%), vomiting (33.3% vs. 21.1%), neutropenia (32.0% vs. 28.1%)

Serious AEs: 37.7% vs. 34.6%

Treatment-related discontinuations: 20.8% vs. 14.9%

Nat Med 2025;31:443-458

Kopetz S,Yoshino T,Van Cutsem E Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial

http://doi.org/10.1038/s41591-024-03443-3

Reviewed by Ulas D. Bayraktar, MD on Mar 31, 2025