If approved by the European Commission later this year, the regimen would become the first targeted therapy approved in the European Union for previously untreated patients with this aggressive form of metastatic colorectal cancer.

The recommendation is based on findings from the Phase 3 Breakwater trial, which evaluated encorafenib plus cetuximab and mFOLFOX6 against standard oxaliplatin-based chemotherapy, with or without bevacizumab, in patients with previously untreated BRAFV600E-mutant metastatic colorectal cancer.

Results showed statistically significant improvements in both progression-free survival and objective response rate, the study’s dual primary endpoints. Median progression-free survival reached 12.8 months in the encorafenib combination arm compared with 7.1 months for chemotherapy with or without bevacizumab.

The study also demonstrated a significant overall survival benefit. Median overall survival was 30.3 months for patients receiving the encorafenib-based regimen compared with 15.1 months in the control group, representing a 51% reduction in the risk of death.

Confirmed objective responses were reported in 65.7% of patients treated with the targeted combination, compared with 37.4% of those receiving chemotherapy with or without bevacizumab.

Eric Ducournau, chief executive officer of Pierre Fabre Laboratories, said: “Today’s positive CHMP opinion marks an important step towards a targeted approach for patients with BRAFV600E-mutant metastatic colorectal cancer. If approved, it would be the only approved targeted therapy in the EU for this patient population in the first-line setting. This milestone reflects Pierre Fabre Laboratories’ commitment to advancing meaningful innovation in oncology and to working in close partnership with the scientific and medical community to address areas of high unmet need.”

The safety profile observed in Breakwater was consistent with the known profiles of the individual medicines. The most frequently reported treatment-related adverse events included nausea, anaemia, diarrhoea, decreased appetite, vomiting, decreased neutrophil count, arthralgia and rash. Grade 3 or 4 treatment-related adverse events occurred in 81.5% of patients, while grade 5 events occurred in 4.3%.

Colorectal cancer remains one of the most common cancers globally, with an estimated 1.9 million new cases diagnosed in 2022. In Europe, more than 500,000 people are diagnosed with the disease each year.

BRAFV600E mutations are found in approximately 8% to 12% of patients with metastatic colorectal cancer and are associated with significantly poorer outcomes than cancers without the mutation. Patients carrying the mutation face around double the risk of mortality compared with those with wild-type BRAF disease.

BRAFTOVI is already approved in Europe in combination with cetuximab for previously treated BRAFV600E-mutant metastatic colorectal cancer, as well as for certain patients with melanoma and non-small cell lung cancer carrying BRAFV600 mutations.

The European Commission will now review the CHMP recommendation before making a final decision on marketing authorisation across the EU.