Merck has announced that the European Commission has approved an update to the Erbitux (cetuximab) EU label, extending its indication to include first‑line use in combination with encorafenib and FOLFOX for adults with BRAF V600E‑mutant metastatic colorectal cancer.
The therapy is also now approved for patients who have received prior systemic treatment.
The first‑line approval is based on results from the phase 3 Breakwater trial, which showed statistically significant and clinically meaningful improvements in objective response rate and progression‑free survival, as well as a significant overall survival benefit.
The cetuximab–encorafenib–FOLFOX combination reduced the risk of death by 51% compared with chemotherapy with or without bevacizumab.
Matthias Wernicke, Head of Global Therapeutic Area Specialty Care at Merck, said: “The approval of Erbitux in combination with encorafenib and FOLFOX marks an important milestone for patients with BRAF V600E-mutant mCRC who can now benefit from a first targeted treatment option in the first-line setting.”
He added: “BRAF V600E-mutant mCRC is associated with a historically poor prognosis and limited effective options. This approval reinforces Erbitux as the backbone of anti-EGFR therapy in colorectal cancer — and reflects our ongoing commitment to addressing unmet needs for patients across the full treatment continuum.”
Breakwater is a phase 3, randomized, active‑controlled, open‑label, multicentre trial conducted by Pfizer in collaboration with Merck and Ono Pharmaceutical. The regimen delivered improvements across all key endpoints versus standard chemotherapy.
Median progression‑free survival was 12.8 months versus 7.1 months, while median overall survival reached 30.3 months versus 15.1 months. Confirmed objective response rate was 65.7% compared with 37.4% in the control arm. Safety profiles were consistent with those of the individual agents.
The cetuximab–encorafenib–FOLFOX regimen has been endorsed as first‑line standard of care in the April 2026 ESMO Clinical Practice Guidelines. Erbitux also remains a standard option in second‑line and beyond, supported by phase 3 Beacon CRC results showing a 39% reduction in risk of death versus irinotecan‑based therapy.
Erbitux is now the first anti‑EGFR therapy approved for both RAS wild‑type and BRAF V600E‑mutant mCRC, supporting personalised treatment across multiple lines of therapy.
