The European Commission has approved Erbitux (cetuximab) in combination with encorafenib and FOLFOX as the first targeted first-line treatment for adults with BRAF V600E-mutant metastatic colorectal cancer, expanding treatment options for patients with an aggressive form of the disease.

The approval is based on results from the Phase 3 Breakwater trial, which demonstrated statistically significant improvements in progression-free survival and overall survival compared with standard chemotherapy with or without bevacizumab.

BRAF V600E mutations occur in around 8–12% of patients with metastatic colorectal cancer and are associated with a particularly poor prognosis. The approval introduces a targeted treatment option earlier in the treatment pathway for this patient population.

In the Breakwater trial, patients receiving cetuximab, encorafenib and FOLFOX achieved a median progression-free survival of 12.8 months compared with 7.1 months for standard treatment, representing a 47% reduction in the risk of disease progression or death.

Median overall survival increased to 30.3 months compared with 15.1 months in the control arm, reducing the risk of death by 51%. The confirmed objective response rate was also higher, at 65.7% compared with 37.4% for standard chemotherapy.

Matthias Wernicke, head of global therapeutic area specialty care in the healthcare business sector of 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.”

The European Commission also approved Erbitux in combination with encorafenib for patients whose disease has progressed following prior systemic therapy, based on results from the Phase 3 Beacon trial.

In Beacon, the combination significantly improved overall survival compared with irinotecan-based treatment, with median overall survival of 9.3 months versus 5.9 months, reducing the risk of death by 39%.

The first-line Breakwater regimen has also been incorporated into the 2026 European Society for Medical Oncology clinical practice guidelines for patients with BRAF V600E-mutant metastatic colorectal cancer.

The latest approval further expands the role of targeted therapies in colorectal cancer, where treatment decisions are increasingly guided by tumour genetics. Earlier access to targeted treatment may improve outcomes for patients whose cancers carry mutations associated with poor prognosis.