Pfizer Shares Positive Data from Phase III BREAKWATER Trial of Braftovi Combination Following Accelerated Approval

News
Article

Being evaluated for the treatment of metastatic colorectal cancer, the combination regimen achieved an objective response rate of 61% compared to 40% for investigator’s choice of chemotherapy.

© Sebastian Kaulitzki - © Sebastian Kaulitzki - stock.adobe.com

Image Credit: © Sebastian Kaulitzki - stock.adobe.com

Pfizer has announced positive results from the Phase III BREAKWATER clinical trial of Braftovi (encorafenib) in combination with cetuximab and mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) in patients with metastatic colorectal cancer with a BRAF V600E mutation. The Braftovi combination regimen demonstrated a clinically meaningful and statistically significant improvement in objective response rate of 61% compared to 40% for patients receiving chemotherapy with or without bevacizumab.1

The estimated median duration of response was 13.9 months for the Braftovi combination and 11.1 months with chemotherapy, with or without bevacizumab. Overall survival data were immature at the time of this most recent analysis. However, Pfizer reports there is a promising trend in favor of the Braftovi treatment regimen. The safety profile of the Braftovi combination was consistent with the known profile of each respective agent with no new safety signals being identified.

In a press release, Scott Kopetz, MD, PhD, 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 said, “Despite the high unmet need in this patient population, prior to the recent encorafenib combination regimen approval, there were no approved biomarker-driven therapies indicated for people with previously untreated BRAF V600E-mutant metastatic colorectal cancer. These data from the BREAKWATER study show the potential for this targeted treatment regimen to become the new standard of care for people with BRAF V600E-mutant metastatic colorectal cancer, for whom long-term disease control is critical.”

The Phase III BREAKWATER trial is a randomized, active-controlled, open-label, multicenter study. Patients were randomized to receive 300 mg of Braftovi orally once daily in combination with cetuximab (discontinued after randomization of 158 patients), 300 mg of Braftovi orally once daily in combination with cetuximab and mFOLFOX6 or mFOLFOX6, FOLFOXIRI, or CAPOX each with or without bevacizumab, which was the control arm.

“These results of this first analysis were the basis for the first approval of a targeted therapy regimen for use in the first-line setting for patients with metastatic colorectal cancer with a BRAF V600E mutation,” Roger Dansey, MD, chief oncology officer, Pfizer, said in the press release. “We are highly encouraged by these response results, which are indicative of the clinically meaningful benefit of BRAFTOVI in reducing tumor size or having no detectable cancer, along with the promising interim analysis of overall survival. We look forward to additional read-outs from the BREAKWATER trial this year.”

In December 2024, Braftovi in combination with cetuximab and mFOLFOX6 received accelerated approval from the FDA under Project FrontRunner, becoming the first and only combination regimen with targeted therapy approved for use as early as first-line for patients with metastatic colorectal cancer with a BRAF V600E mutation.2

In a press release from the time, Kopetz said, “Historically, treatment options have been limited and outcomes poor for patients diagnosed with metastatic colorectal cancer with BRAF mutations. As the first and only combination regimen featuring a BRAF-targeted therapy for this patient population, usable even in first-line treatment, the encorafenib regimen has demonstrated high response rates that are rapid and durable. This represents an encouraging sign of continued disease control and a source of renewed hope for patients.”

References

1. Pfizer’s BRAFTOVI® Combination Regimen Demonstrates Improved Response in Patients with BRAF V600E-Mutant Metastatic Colorectal Cancer. News release. Pfizer. January 25, 2025. Accessed January 27, 2025. https://www.businesswire.com/news/home/20250124736884/en/Pfizer%E2%80%99s-BRAFTOVI%C2%AE-Combination-Regimen-Demonstrates-Improved-Response-in-Patients-with-BRAF-V600E-Mutant-Metastatic-Colorectal-Cancer

2. U.S. FDA Approves Pfizer’s BRAFTOVI® Combination Regimen as First-Line Treatment of BRAF V600E-Mutant Metastatic Colorectal Cancer. News release. Pfizer. December 20, 2024. Accessed January 27, 2025. https://www.businesswire.com/news/home/20241210321033/en/U.S.-FDA-Approves-Pfizer%E2%80%99s-BRAFTOVI%C2%AE-Combination-Regimen-as-First-Line-Treatment-of-BRAF-V600E-Mutant-Metastatic-Colorectal-Cancer

Recent Videos
Related Content
© 2025 MJH Life Sciences

All rights reserved.