Published: May 30, 2025
Pfizer shared results from the BRAFTOVI BREAKWATER trial at ASCO 2025. The trial tested BRAFTOVI® (encorafenib) with cetuximab and mFOLFOX6 in patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC). This post details the findings, based on a Pfizer press release. A video summary is also available.
What Is the BRAFTOVI BREAKWATER Trial?
The BRAFTOVI BREAKWATER trial is a Phase 3 study. It compared BRAFTOVI with cetuximab and mFOLFOX6 to standard chemotherapy in 479 patients with BRAF V600E-mutant mCRC. Specifically, 236 patients received the BRAFTOVI regimen, while 243 got standard treatments like mFOLFOX6 or CAPOX, with or without bevacizumab. The trial measured objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
Survival Results from the Trial
The BRAFTOVI BREAKWATER trial showed clear survival benefits. Below are the key results.
Overall Survival
The BRAFTOVI regimen cut the risk of death by 51% (Hazard Ratio: 0.49; 95% CI, 0.38-0.63; p<0.0001). Patients on BRAFTOVI lived a median of 30.3 months. In contrast, the standard group lived 15.1 months. These data came from a second interim analysis.
Progression-Free Survival
The trial also reduced disease progression risk by 47% (Hazard Ratio: 0.53; 95% CI, 0.41-0.68; p<0.0001). Median PFS was 12.8 months for BRAFTOVI patients, compared to 7.1 months for the control group. Independent reviewers confirmed these results.
Response Rates
The BRAFTOVI group had a 65.7% response rate (95% CI, 59.4-71.4). The control group’s rate was 37.4% (95% CI, 31.6-43.7). BRAFTOVI patients responded for a median of 13.9 months, versus 11.1 months for controls.
Is the Treatment Safe?
The BRAFTOVI regimen’s safety matched known profiles. Common side effects included nausea, anemia, and diarrhea. About 13.8% of patients stopped BRAFTOVI due to side effects. No unexpected safety issues appeared.
Why These Results Matter
Colorectal cancer is the third most common cancer worldwide. BRAF V600E mutations affect 8-12% of mCRC cases and double mortality risk. Elena Élez, M.D., Ph.D., said, “These are the first survival data for BRAF-mutant colorectal cancer in first-line treatment.” Michael Sapienza from the Colorectal Cancer Alliance added, “These results address outcomes for high-risk patients.”
FDA Approval Status
In December 2024, the FDA gave accelerated approval to BRAFTOVI for BRAF V600E-mutant mCRC. This was part of Project FrontRunner. Pfizer is now discussing full approval based on these survival results.
Learn More About the Trial
Want more details? Visit Pfizer’s APLS page for plain language summaries, available from May 22, 2025. You can also read the full Pfizer press release or the New England Journal of Medicine article.
Watch the Trial Video
See the BRAFTOVI BREAKWATER trial results in our ASCO 2025 video:https://artifacts.grokusercontent.com/[Insert%20Video%20URL]
Final Thoughts
The BRAFTOVI BREAKWATER trial at ASCO 2025 showed better survival for BRAF V600E-mutant mCRC patients. These results may lead to a new treatment standard. Stay updated via Pfizer’s website.
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