Pfizer announced positive results from the Phase 3 BREAKWATER trial evaluating BRAFTOVI (encorafenib) in combination with cetuximab (marketed as ERBITUX ) and mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) in patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation.

“Despite the high unmet need in this patient population, prior to the recent encorafenib combination regimen approval, there were no approved biomarker-driven therapies indicated for people with previously untreated BRAF V600E -mutant metastatic colorectal cancer,” said Scott Kopetz, M.D., Ph.D., FACP, Professor and Deputy Chair of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center and co-principal investigator of the BREAKWATER trial.

“These data from the BREAKWATER study show the potential for this targeted treatment regimen to become the new standard of care for people with BRAF V600E -mutant metastatic colorectal cancer, for whom long-term disease control is critical.”

Overall survival (OS) data were immature at the time of this analysis but demonstrated a promising trend in favor of BRAFTOVI plus cetuximab and mFOLFOX6 compared to patients receiving chemotherapy with or without bevacizumab. Median OS with BRAFTOVI plus cetuximab with chemotherapy was not estimable (95% CI: 19.8-NE) and 14.6 months (95% CI: 13.4-NE) with chemotherapy with or without bevacizumab (Hazard Ratio [HR]: 0.47, 95% CI: 0.318-0.691). The BREAKWATER trial is ongoing for OS and progression-free survival (PFS), with PFS results expected in 2025.

“These results of this first analysis were the basis for the first approval of a targeted therapy regimen for use in the first-line setting for patients with metastatic colorectal cancer with a BRAF V600E mutation,” said Roger Dansey, M.D., Chief Oncology Officer, Pfizer. “We are highly encouraged by these response results, which are indicative of the clinically meaningful benefit of BRAFTOVI in reducing tumor size or having no detectable cancer, along with the promising interim analysis of overall survival. We look forward to additional read-outs from the BREAKWATER trial this year.”