Groundbreaking Cancer Treatment Shows Significant Survival Benefits
A recent press release from Pfizer Inc. (NYSE: PFE) announced remarkable 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. As reported by Pfizer, the trial demonstrated a 51% risk reduction in death compared to standard-of-care treatment.
According to the source, Pfizer, the BREAKWATER trial showed that the BRAFTOVI combination regimen reduced the risk of death by 51% compared to standard-of-care chemotherapy with or without bevacizumab (Hazard Ratio [HR] 0.49; 95% Confidence Interval [CI], 0.38, 0.63). As noted in the press release, “The BRAFTOVI combination helped significantly reduce the risk of disease progression or death, potentially altering the course of disease for people with metastatic colorectal cancer with a BRAF V600E mutation,” said Johanna Bendell, M.D., Chief Oncology Development Officer, Pfizer.
The trial also found that the BRAFTOVI combination regimen demonstrated a 47% risk reduction in disease progression or death compared to standard-of-care chemotherapy with or without bevacizumab (HR 0.53; 95% CI, 0.41, 0.68). Pfizer stated that these data will be presented today in an oral presentation (Abstract LBA3500) at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and have been simultaneously published in the New England Journal of Medicine.
Colorectal cancer (CRC) is the third most common type of cancer in the world, with approximately 1.8 million new diagnoses in 2022. BRAF mutations are estimated to occur in 8-12% of people with mCRC and represent a poor prognosis. The BRAF V600E mutation is the most common BRAF mutation, and the risk of mortality in patients with CRC harboring this mutation is more than double that of patients with no known BRAF mutation present.
As reported, the updated objective response rate (ORR) by BICR confirmed the improvement previously observed with the BRAFTOVI combination regimen compared to patients receiving chemotherapy with or without bevacizumab (65.7%; 95% CI, 59.4, 71.4 and 37.4%; 95% CI, 31.6, 43.7, respectively). Pfizer’s press release stated that “The BREAKWATER results are the first promising survival outcomes ever reported for BRAF-mutant metastatic colorectal cancer in the first-line setting, representing a practice-changing breakthrough for patients.”
The BRAFTOVI combination regimen received accelerated approval by the U.S. Food and Drug Administration (FDA) in December 2024 for patients with BRAF V600E-mutant mCRC based on a clinically meaningful and statistically significant improvement in confirmed ORR in treatment-naïve patients. Continued approval for this indication is contingent upon verification of clinical benefit.
Pfizer is continuing its commitment to help non-scientists understand the latest findings with the development of abstract plain language summaries (APLS) for company-sponsored research being presented. Those interested in learning more can visit www.Pfizer.com/apls to access the summaries.
BRAFTOVI is an oral small molecule kinase inhibitor that targets BRAF V600E. Inappropriate activation of proteins in the MAPK signaling pathway (RAS-RAF-MEK-ERK) has been shown to occur in certain cancers, including CRC. Pfizer has exclusive rights to BRAFTOVI in the U.S., Canada, Latin America, Middle East, and Africa.
As stated by Elena Élez, M.D., Ph.D., senior investigator at Vall d’Hebron Institute of Oncology in Barcelona, Spain, and co-principal investigator of the BREAKWATER trial, “The risk of death for patients with BRAF V600E-mutant metastatic colorectal cancer is more than double compared to those with no known mutation.”
The information contained in this article is as of May 30, 2025, and Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
References:
1. American Cancer Society. Global Cancer Facts & Figures 5th Edition. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/global-cancer-facts-and-figures/global-cancer-facts-and-figures-2024.pdf. Last accessed: March 2025.
2. Josep Tabernero et al., The Evolving Treatment Landscape in BRAF-V600E–Mutated Metastatic Colorectal Cancer. Am Soc Clin Oncol Educ Book 42, 254-263(2022). DOI:10.1200/EDBK_349561
3. Safaee Ardekani G, Jafarnejad SM, Tan L, et al. The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and meta-analysis. PloS ONE. 2012;7(10):e47054.
4. Schirripa M, Biason P, Lonardi S, et al. Class 1, 2, and 3 BRAF-Mutated Metastatic Colorectal Cancer: A Detailed Clinical, Pathologic, and Molecular Characterization. Clin Cancer Res. 2019;25(13):3954-3961. doi:10.1158/1078-0432.CCR-19-0311
5. Kopetz S, Yoshino T, Van Cutsem E, et al. Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial. Nat Med. 2025;31(3):901-908. doi:10.1038/s41591-024-03443-3
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