The BREAKWATER phase 3 trial, published in Nature Medicine, has demonstrated that encorafenib plus cetuximab (EC) with mFOLFOX6 significantly improves objective response rates compared to standard chemotherapy in BRAF V600E-mutant metastatic colorectal cancer (mCRC). The study reports a confirmed objective response rate of 60.9% with EC+mFOLFOX6 compared to 40.0% with standard chemotherapy, with a median duration of response of 13.9 months versus 11.1 months. The interim analysis of overall survival shows a hazard ratio of 0.47, suggesting a clear survival benefit for EC+mFOLFOX6.
The safety profile remains consistent with known adverse events of each treatment, with manageable toxicity. These findings indicate that EC+mFOLFOX6 could become a new first-line standard of care for patients with BRAF V600E-mutant mCRC, a historically challenging-to-treat population. The final analysis of progression-free survival is ongoing and will provide further insights into the long-term benefits of this regimen.
