Pfizer’s BRAFTOVI regimen nearly doubles median progression free survival in metastatic colorectal cancer

Cohort 3 analysis from the Phase 3 BREAKWATER study showed a 56% reduction in the risk of disease progression or death compared with a traditional chemotherapy regimen, alongside an overall survival benefit reflected in a 44% reduction in the risk of death. BRAFTOVI in combination with cetuximab and fluorouracil based chemotherapy is the only approved targeted regimen for BRAF V600E mutant metastatic colorectal cancer.

Pfizer has shared detailed progression free and overall survival results from Cohort 3, a randomised cohort of the Phase 3 BREAKWATER trial, evaluating BRAFTOVI (encorafenib) in combination with cetuximab (marketed as ERBITUX) and FOLFIRI (fluorouracil, leucovorin, and irinotecan) versus FOLFIRI with or without bevacizumab in patients with previously untreated metastatic colorectal cancer (mCRC) carrying a BRAF V600E mutation. The results will be presented in a late breaking oral presentation (Abstract LBA3503) at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and published simultaneously in the Annals of Oncology.

As previously reported, Cohort 3 met its primary endpoint of objective response rate by blinded independent central review. Results for the key secondary endpoint of progression free survival by blinded independent central review, being presented at ASCO, show that median progression free survival was nearly doubled with the BRAFTOVI combination regimen, reaching 15.2 months compared with 8.3 months for the comparator. A clinically meaningful and statistically significant 56% reduction in the risk of disease progression or death was observed for patients treated with the BRAFTOVI combination regimen versus the comparator (hazard ratio 0.44; 95% confidence interval 0.27 to 0.70; p=0.0002).

Updated overall survival, a descriptive secondary endpoint, showed a 44% reduction in the risk of death for patients on the BRAFTOVI combination regimen compared with the comparator (hazard ratio 0.56; 95% confidence interval 0.34 to 0.94), at a median follow up of approximately 20 months for both arms. At 18 months, an estimated 72% of patients receiving the BRAFTOVI combination regimen were expected to be alive, compared with 54.5% of those on the comparator. Median overall survival had not been reached for the BRAFTOVI combination regimen, versus a median of 20.3 months for the comparator.

“For people with BRAF V600E-mutant metastatic colorectal cancer – a disease that historically has had no targeted treatment options and poor outcomes – these results strengthen confidence in how we can treat this disease,” 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. “A nearly 60% reduction in risk of disease progression or death, combined with prolonged overall survival, reinforces the role of encorafenib in combination with cetuximab and FOLFIRI as a standard of care in the first-line setting for this patient population.”

“These compelling results add to a robust body of evidence demonstrating the efficacy of the BRAFTOVI combination treatment across two different established chemotherapy regimens in BRAF V600E-mutant metastatic colorectal cancer,” said Jeff Legos, Chief Oncology Officer, Pfizer. “These findings reaffirm the established role of the BRAFTOVI combination regimen as a cornerstone of first-line treatment for patients and families facing this challenging diagnosis.”

In the Cohort 3 analysis, the safety profile of BRAFTOVI in combination with cetuximab and FOLFIRI remained consistent with the known safety profile of each agent in the regimen, and no new safety signals were identified. The most common adverse events (occurring in 25% or more of patients) in the BRAFTOVI regimen were nausea, diarrhoea, vomiting, anaemia, alopecia, fatigue, decreased neutrophil count, constipation, decreased appetite, neutropenia, arthralgia, asthenia, and abdominal pain. Grade 3 or higher adverse events (all causality) occurred in 70.4% of patients receiving BRAFTOVI in combination with cetuximab and FOLFIRI, compared with 80.9% of patients on FOLFIRI with or without bevacizumab. Treatment discontinuation occurred in 15.5% of patients on the BRAFTOVI combination, compared with 10.3% of those on FOLFIRI.

On the basis of the totality of the Phase 3 and Cohort 3 data from BREAKWATER, BRAFTOVI in combination with cetuximab and fluorouracil based chemotherapy received full approval with an expanded indication from the US Food and Drug Administration for patients with BRAF V600E mutant mCRC in February 2026, offering flexibility in the chemotherapy regimen used.

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Related Topics and Keywords

braftovi, Metastatic Colorectal Cancer, Pfizer, Pfizer’s BRAFTOVI®