The European Commission has approved BRAFTOVI in combination with cetuximab and FOLFOX as a first-line treatment for adults with BRAFV600E-mutant metastatic colorectal cancer following positive Phase 3 trial results.

Laboratoires Pierre Fabre has secured European Commission approval for BRAFTOVI (encorafenib) in combination with cetuximab and FOLFOX for the first-line treatment of adults with BRAFV600E-mutant metastatic colorectal cancer (mCRC).

The decision makes the regimen the first and only BRAF-targeted therapy approved in the European Union for previously untreated patients with this form of colorectal cancer.

Approval was supported by data from the Phase 3 Breakwater trial, which compared encorafenib in combination with cetuximab and mFOLFOX6 against oxaliplatin-based chemotherapy with or without bevacizumab in patients with previously untreated BRAFV600E-mutant mCRC.

Results showed statistically significant improvements across both primary endpoints of progression-free survival and objective response rate.

Median progression-free survival reached 12.8 months in the encorafenib combination arm compared with 7.1 months for patients receiving standard chemotherapy.

The study also demonstrated a significant overall survival benefit. Median overall survival was 30.3 months for patients receiving the BRAFTOVI regimen compared with 15.1 months in the chemotherapy arm, representing a 51% reduction in the risk of death.

Eric Ducournau, chief executive officer of Laboratoires Pierre Fabre, said: “We are extremely pleased to be able to expand the availability of encorafenib in combination with cetuximab and FOLFOX for the first-line treatment of adult patients with BRAFV600E-mutant mCRC. Today’s EC decision for this regimen marks the approval of the only targeted therapy in the EU for this patient population in the first-line setting and an important milestone in that it helps to address a significant unmet need for patients and clinicians, for whom treatment options have been limited.”

Colorectal cancer remains one of the most common cancers globally, with approximately 1.9 million new cases reported in 2022. Patients whose tumours harbour a BRAFV600E mutation typically experience poorer outcomes than those with wild-type BRAF disease.

According to Pierre Fabre, BRAF mutations occur in around 8-12% of patients with metastatic colorectal cancer, with BRAFV600E representing the most common mutation subtype.

The Breakwater study enrolled patients with previously untreated stage IV colorectal cancer carrying the BRAFV600E mutation. The trial evaluated BRAFTOVI plus cetuximab with or without chemotherapy against chemotherapy regimens with or without bevacizumab.

The treatment combination also improved response rates. In the primary analysis population, objective response rates reached 60.9% compared with 40% in the control arm.

Safety findings were consistent with the known profiles of the individual medicines. The most common adverse events in the BRAFTOVI combination arm included nausea, anaemia, diarrhoea, decreased appetite, vomiting, decreased neutrophil count, arthralgia and rash.

Nùria Perez-Cullel, head of medical, patient, and consumer affairs at Laboratoires Pierre Fabre, said: “We are committed to bringing this treatment combination to patients with BRAFV600E-mutant mCRC, where limited treatment options, specifically for these patients, exist. We continue to advance our clinical development efforts to help bring new targeted cancer therapies to patients who need them the most.”

BRAFTOVI in combination with cetuximab previously received European approval in 2020 for patients with BRAFV600E-mutant metastatic colorectal cancer who had already received systemic therapy. The latest decision extends use of the regimen into the first-line setting.