The European Commission (EC) has approved encorafenib in combination with cetuximab and FOLFOX for the first-line treatment of adult patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC).

The approval is based on the results from the Phase 3 BREAKWATER trial, which assessed the efficacy and safety of encorafenib in combination with cetuximab and mFOLFOX6 in patients with previously untreated BRAF V600E-mutant mCRC, compared with oxaliplatin-based chemotherapy, with or without bevacizumab.
 
Eric Ducournau, Chief Executive Officer, 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 BRAF V600E-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.”
 
In the Phase 3 BREAKWATER trial, the regimen of encorafenib in combination with cetuximab and mFOLFOX6 showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with oxaliplatin-based chemotherapy with or without bevacizumab (median PFS 12.8 vs. 7.1 months; hazard ratio [HR] 0.53; 95% confidence interval [CI], 0.41 to 0.68; P<0.001), and demonstrated a statistically significant improvement in the dual primary endpoint of ORR in the primary analysis set (60.9% vs. 40.0%; odds ratio 2.44; 95% CI: 1.40–4.25; P<0.001).

A confirmed ORR was observed in 65.7% of patients (95% CI, 59.4 to 71.4) compared to 37.4% (95% CI, 31.6 to 43.7) in the oxaliplatin-based chemotherapy with or without bevacizumab group in the overall population.

In an interim analysis, the encorafenib regimen demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared with oxaliplatin-based chemotherapy with or without bevacizumab (median OS, 30.3 vs. 15.1 months; HR 0.49; 95% CI, 0.38 to 0.63; P<0.001), reducing the risk of death by 51%.
 
The most frequent adverse events (AEs) during treatment (≥30%) in the encorafenib in combination with cetuximab and mFOLFOX6 group were nausea (53.9%), anaemia (46.1%), diarrhoea (41.8%), decreased appetite (37.5%), vomiting (36.2%), decreased neutrophil count (34.1%), arthralgia (31.5%), and rash (30.2%).

AEs of grade 3 or 4 occurred in 81.5%, and grade 5 in 4.3%. In the oxaliplatin-based chemotherapy with or without bevacizumab group, diarrhoea (50.2%) and nausea (49.8%) were the most frequent AEs.

AEs of grade 3 or 4 occurred in 66.8%, and grade 5 in 4.4%. Safety profiles were consistent with those known for each agent.
 
"This EC approval underscores our commitment to improving care for cancer patients, in this case in colorectal cancer, a disease where the incidence continues to rise globally”3 said Nùria Perez-Cullel, Head of Medical, Patient, and Consumer Affairs, Laboratoires Pierre Fabre.

“We are committed to bringing this treatment combination to patients with BRAF V600E- 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.”
 
Encorafenib in combination with cetuximab was approved by the EC in 2020 for the treatment of adults with BRAF V600E-mutated mCRC who had received prior systemic therapy, supported by results from the randomised, controlled, open-label, multi-centre Phase 3 BEACON CRC trial.

Source: Laboratoires Pierre Fabre