First-line encorafenib + cetuximab + mFOLFOX6 doubles survival to 30 mo in BRAF-V600E metastatic CRC

Encorafenib (BRAF V600E inhibitor) plus cetuximab (EGFR mAb) and mFOLFOX6 chemotherapy was tested against investigator-choice oxaliplatin-based chemotherapy ± bevacizumab in the phase 3 BREAKWATER trial (NCT04607421). Among previously untreated BRAF-V600E mCRC patients, EC+mFOLFOX6 delivered a 65-7% ORR (vs 37%) and a median PFS of 12.8 mo versus 7.1 mo for standard care (HR 0.53, P < 0.001). Interim overall survival reached 30.3 mo versus 15.1 mo (HR 0.49, P < 0.001), **the first front-line regimen in this genotype to crack the 2-year mark.**Grade ≥3 serious AEs occurred in 46% on the triplet versus 39% with chemo; toxicity mirrored known profiles of each agent without new safety signals.