The BRAFTOVI combination regimen is the only approved targeted regimen for first-line BRAF-V600E mutant metastatic colorectal cancer
Pfizer Inc. has received full approval from the U.S. Food and Drug Administration for BRAFTOVI encorafenib used together with cetuximab, marketed as ERBITUX, and fluorouracil based chemotherapy for adults with metastatic colorectal cancer that carries the BRAF V600E mutation. The decision follows results from the global Phase 3 BREAKWATER trial, identified as NCT04607421. The regimen had previously been cleared under accelerated approval in December 2024 based on tumor response data. The agency has now converted that status to full approval after reviewing additional findings showing meaningful improvements in progression free survival and overall survival in patients treated with BRAFTOVI plus cetuximab and mFOLFOX6. Additional response data from a separate study group evaluating BRAFTOVI with cetuximab and FOLFIRI also supported the decision.
Aamir Malik, Executive Vice President and Chief U.S. Commercial Officer at Pfizer, said the approval represents an important step forward for patients facing an aggressive and difficult to treat form of colorectal cancer. He noted that the strong clinical results seen in the BREAKWATER study confirm that this targeted combination can change outcomes for people with BRAF V600E mutant metastatic disease. He added that as the only targeted regimen in this setting to demonstrate significant improvements in key measures of patient benefit, the therapy has the potential to reshape first line treatment and set a new benchmark in care. Malik emphasized that the milestone reflects Pfizer’s continued focus on delivering innovative cancer therapies that address urgent unmet needs.
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Scott Kopetz, 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, said the approval gives physicians greater certainty when considering encorafenib plus cetuximab with fluorouracil based chemotherapy as an initial treatment option. He explained that the study generated statistically significant data across major clinical endpoints, providing oncologists with solid evidence to guide treatment decisions that can directly influence patient survival and disease control.
Safety findings from the study were consistent with the established profiles of the individual medicines in each combination, and no new safety concerns were identified. In patients treated with the mFOLFOX6 regimen, commonly reported side effects included peripheral neuropathy, nausea, fatigue, diarrhea, decreased appetite, rash, vomiting, bleeding events, abdominal pain, joint pain, fever, and constipation. For those receiving the FOLFIRI regimen, the most frequent adverse events included nausea, diarrhea, fatigue, vomiting, hair loss, constipation, abdominal pain, decreased appetite, and rash. Fourteen percent of patients in the mFOLFOX6 group discontinued BRAFTOVI due to adverse reactions, while nine percent of patients in the FOLFIRI group stopped treatment for the same reason. Rates of chemotherapy discontinuation due to side effects were similar between treatment arms.
The BRAFTOVI combination with mFOLFOX6 is currently under review by European regulators, where Pierre Fabre Laboratories holds exclusive commercialization rights, and it has already secured approvals in several other countries, expanding access to this targeted option for eligible patients worldwide.
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