Promising New First-Line Treatment for BRAF V600E–Mutated Metastatic Colorectal Cancer
Updated results from the international BREAKWATER phase III trial show that patients with BRAF V600E-mutated metastatic colorectal cancer may live significantly longer when treated with a combination of encorafenib, cetuximab, and mFOLFOX6 chemotherapy, compared to the current standard of care for this subset of patients, which involves chemotherapy with or without bevacizumab.
Key Findings:
- Patients who received encorafenib + cetuximab + mFOLFOX6 chemotherapy had a median overall survival of 30.3 months, compared to 15.1 months with standard chemotherapy (with or without bevacizumab).
- The time before the cancer worsened (progression-free survival) was also longer – 12.8 months vs 7.1 months.
- Response rates were significantly higher with the new combination: 65.7% compared to 37.4% with standard treatment.
- Responses also lasted longer – more patients maintained a benefit from treatment for at least 6 and 12 months.
Safety:
The combination was generally well tolerated, with no unexpected side effects. The most common adverse effects were nausea, anemia, and diarrhea. Serious side effects occurred in about 46% of patients on the new regimen – comparable to standard treatment – and most patients were able to stay on therapy without needing major dose reductions.
Take-home message:
These updated results confirm that encorafenib + cetuximab + mFOLFOX6 chemotherapy offers a substantial improvement in survival and disease control for patients with BRAF V600E-mutated metastatic colorectal cancer. Based on earlier data from this study, the Food and Drug Administration (FDA) in the United States has already granted accelerated approval of this combination as a first-line treatment for this patient population. The combination therapy is currently under reimbursement review in Canada by Canada’s Drug Agency.
