Pfizer has announced groundbreaking results from the Phase 3 BREAKWATER trial, showcasing the effectiveness of its BRAFTOVI® (encorafenib) combination regimen in the treatment of metastatic colorectal cancer (mCRC) with the BRAF V600E mutation. The trial highlights significant improvements in both progression-free survival (PFS) and overall survival (OS), establishing BRAFTOVI as a potential new standard of care for this patient population.
The trial evaluated the BRAFTOVI combination with cetuximab (marketed as ERBITUX®) and mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) compared to chemotherapy alone or with bevacizumab. The results demonstrated a clinically meaningful improvement in PFS, one of the dual primary endpoints, and a statistically significant improvement in OS as a key secondary endpoint.
“We are extremely pleased with the clinically meaningful progression-free survival and overall survival results from the BREAKWATER study, which have the potential to be practice-changing for this patient population that has historically had limited treatment options and poor outcomes,” said Roger Dansey, M.D., Chief Oncology Officer, Pfizer. “The BRAFTOVI regimen is emerging as a new standard of care as the first targeted therapy approved for use as early as first-line for patients with mCRC with a BRAF V600E mutation. We look forward to discussing these data with global health authorities to bring this treatment to more patients around the world, as soon as possible.”
In December 2024, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the BRAFTOVI combination for treatment-naïve patients with BRAF V600E-mutant mCRC based on improved objective response rate (ORR). The ORR findings were presented at the 2025 American Society of Clinical Oncology Gastrointestinal Cancer Symposium (ASCO GI) and published in Nature Medicine in January 2025.
The safety profile of BRAFTOVI in combination with cetuximab and mFOLFOX6 remained consistent with known profiles of the individual agents, with no new safety concerns raised. Pfizer plans to share these results with the FDA and other global health authorities to secure full regulatory approval for the regimen.
About BREAKWATER and Colorectal Cancer
The Phase 3 BREAKWATER trial was an active-controlled, multicenter study that randomized patients to receive the BRAFTOVI combination or other standard chemotherapy regimens. The dual primary endpoints were objective response rate (ORR) and progression-free survival (PFS), both of which were met during the trial.
Colorectal cancer (CRC) remains a significant global health issue, with over 1.8 million new cases diagnosed in 2022 and it being the second leading cause of cancer-related deaths. Patients with the BRAF V600E mutation, which occurs in 8-12% of mCRC cases, face a particularly poor prognosis with limited treatment options. The success of the BRAFTOVI combination regimen in the BREAKWATER study marks a significant step forward in addressing this unmet medical need.
With these promising results, Pfizer is optimistic about bringing this innovative treatment to patients worldwide, offering new hope for those battling mCRC with BRAF V600E mutations.
