Multinational phase 3 trial of first-line encorafenib, cetuximab, and mFOLFOX6 in BRAF-mutated metastatic colorectal cancer

The multinational phase 3 BREAKWATER trial randomized patients with previously untreated BRAF V600E-mutated metastatic colorectal cancer (mCRC) to encorafenib plus cetuximab (EC), EC plus mFOLFOX6, or standard of care (SOC; chemotherapy with or without bevacizumab). Significantly longer progression-free survival was seen with EC plus mFOLFOX6 than with SOC (median 12.8 versus 7.1 months; HR 0.53; p<0.001). In an interim analysis, overall survival was significantly longer with EC plus mFOLFOX6 than with SOC (median 30.3 versus 15.1 months; HR 0.49; p<0.001). The incidence of serious adverse events during treatment was 46.1% with EC plus mFOLFOX6 and 38.9% with SOC.