cetuximab + encorafenib + fluorouracil + leucovorin + oxaliplatin

Erbitux + encorafenib + fluorouracil + leucovorin + oxaliplatin (also known as the BREAKWATER regimen or EC+mFOLFOX6) is a combination therapy regimen used for the treatment of patients with metastatic colorectal cancer (mCRC) harboring a BRAF V600E mutation. The regimen combines encorafenib (Braftovi), an oral small-molecule BRAF kinase inhibitor, with cetuximab (Erbitux), an epidermal growth factor receptor (EGFR)-targeting monoclonal antibody, and a chemotherapy backbone of modified FOLFOX6 (mFOLFOX6), which consists of fluorouracil (5-FU), leucovorin, and oxaliplatin. Encorafenib selectively inhibits the BRAF V600E kinase, but its inhibition can lead to EGFR-mediated reactivation of the MAPK pathway; the addition of cetuximab blocks this feedback loop. The mFOLFOX6 backbone provides additional cytotoxic activity through DNA damage (oxaliplatin) and thymidylate synthase inhibition (fluorouracil, enhanced by leucovorin). Developed by Pfizer, the combination received FDA approval in February 2026 (following an accelerated approval in December 2024) as a first-line treatment for BRAF V600E-mutant mCRC based on the Phase 3 BREAKWATER trial, which demonstrated significant improvements in progression-free survival and overall survival compared to standard-of-care chemotherapy.

Other names

Braftovi + Erbitux + fluorouracil + leucovorin + oxaliplatinBraftovi + Erbitux + mFOLFOX6BREAKWATER regimencetuximab + encorafenib + fluorouracil + leucovorin + oxaliplatinEC+mFOLFOX6EC-mFOLFOX6EC-mFOLFOX-6EC-mFOLFOX 6encorafenib + cetuximab + fluorouracil + leucovorin + oxaliplatinencorafenib + cetuximab + mFOLFOX6Erbitux + encorafenib + fluorouracil + leucovorin + oxaliplatin