Encorafenib Plus Cetuximab and mFOLFOX6 Improves Survival for Patients With BRAF V600E-Mutated Metastatic Colorectal Cancer
According to updated interim analysis results from the phase 3 BREAKWATER trial, encorafenib plus cetuximab and mFOLFOX6 improved survival compared to standard of care among previously untreated patients with BRAF V600E-mutated metastatic colorectal cancer.
“BRAF V600E-mutated metastatic colorectal cancer has emerged as a distinct subtype of this disease and is characterized by a poorer prognosis and lower responses to chemotherapy,” stated Elena Elez, MD, PhD, Vall d'Hebron Hospital, Barcelona, Spain, and coauthors. “Results from the safety lead-in portion of the trial showed encouraging responses and progression-free survival” with encorafenib plus cetuximab and mFOLFOX6.
In this open-label study, researchers randomized 637 patients on a 1-to-1-to-1 basis to receive encorafenib (300 mg once daily) plus cetuximab (500 mg/m2 once every 2 weeks) either alone (n = 158) or in combination with mFOLFOX6 (n = 236), or the standard-of-care treatment of chemotherapy alone (n = 243) until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). Key secondary end points included overall survival (OS) and safety.
At analysis, median PFS was 12.8 months in the encorafenib plus cetuximab and mFOLFOX6 arm and 7.1 months in the standard of care arm (hazard ratio [HR] 0.53; 95% confidence interval [CI], 0.41 to 0.68; P < .001). Median OS was 30.3 months in the encorafenib plus cetuximab and mFOLFOX6 arm and 15.1 months in the standard of care arm (HR 0.49; 95% CI, 0.38 to 0.63; P < .001). Adverse events were reported in 46.1% and 38.9% of patients, respectively.
“The BREAKWATER trial showed significant results for the two primary end points and the key secondary end point, with significant improvements with [encorafenib plus cetuximab and mFOLFOX6] over standard care,” concluded Dr Elez et al.
Source:
Elez E, Yoshino T, Shen L, et al. Encorafenib, cetuximab, and mFOLFOX6 in BRAF-mutated colorectal cancer. N Engl J Med. Published online: May 30, 2025. doi: 10.1056/NEJMoa2501912
