A new first-line standard-of-care for BRAFV600E-mutated mCRC

The combination of the BRAF inhibitor encorafenib and the anti-EGFR antibody cetuximab is the standard-of-care (SOC) second-line treatment for patients with BRAF^V600E-mutated metastatic colorectal cancers (mCRC; 8–12% of patients). Now, results from the phase III BREAKWATER trial demonstrate the efficacy of encorafenib–cetuximab plus mFOLFOX6 chemotherapy as a first-line treatment for these patients.

Patients with previously untreated BRAF^V600E-mutated mCRC were randomly assigned to receive encorafenib–cetuximab, encorafenib–cetuximab plus mFOLFOX6 (triplet combination) or physician’s choice of SOC chemotherapy. After a protocol amendment, enrolment in the encorafenib–cetuximab group was stopped and patients were randomly assigned to receive triplet combination (n = 236) versus SOC chemotherapy (n = 243). Progression-free survival (PFS) and objective response rate (ORR) were the co-primary end points.