Pfizer Inc. (NYSE: PFE) has announced that the U.S. Food and Drug Administration (FDA) has granted approval for BRAFTOVI® (encorafenib) in combination with cetuximab (marketed as ERBITUX®) and mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) as a treatment for patients with metastatic colorectal cancer (mCRC) harboring the BRAF V600E mutation. This approval follows the Phase 3 BREAKWATER trial, which demonstrated a significant improvement in both response rate and durability of response among patients treated with this combination regimen. This marks a crucial step forward in addressing the high unmet need for effective therapies for this aggressive form of colorectal cancer.
The approval is based on results from the BREAKWATER trial, which enrolled treatment-naïve patients with BRAF V600E-mutant mCRC. The trial showed a 61% overall response rate (ORR) for patients treated with BRAFTOVI, cetuximab, and mFOLFOX6, compared to a 40% ORR for those receiving the standard chemotherapy regimen with or without bevacizumab (p=0.0008). The combination therapy also demonstrated a median duration of response (DoR) of 13.9 months, compared to 11.1 months for the chemotherapy group. These promising results indicate the potential of the BRAFTOVI regimen to offer rapid, durable responses and greater disease control for this hard-to-treat patient population.
Dr. Scott Kopetz, Professor at The University of Texas MD Anderson Cancer Center, emphasized the significance of this development, noting that BRAF-mutant mCRC has long been associated with poor outcomes. He noted that the long-acting BRAF-targeted therapy in the BRAFTOVI combination could offer substantial improvements in treatment convenience, particularly with the possibility of weekly dosing instead of daily injections. This breakthrough provides renewed hope for patients battling this aggressive form of cancer.
Pfizer’s Chief Oncology Officer, Dr. Chris Boshoff, highlighted the company’s commitment to targeted therapies for molecular-driven cancers, particularly BRAF-mutant tumors. This approval adds to Pfizer’s legacy in BRAF-related cancers and represents a key milestone in making targeted treatment options available to patients with BRAF V600E-mutant mCRC. Dr. Boshoff also mentioned ongoing efforts to expand the company’s portfolio, including future work on next-generation brain-penetrant BRAF inhibitors.
The safety profile of BRAFTOVI combined with cetuximab and mFOLFOX6 was consistent with the known safety profiles of the individual components. The most common side effects (≥25%) included peripheral neuropathy, nausea, fatigue, rash, diarrhea, and decreased appetite. Some patients experienced adverse reactions leading to permanent discontinuation, though no new safety concerns were identified.
This approval is part of Pfizer’s continued effort to advance treatments for rare and difficult-to-treat cancers. The FDA’s Project FrontRunner, designed to accelerate cancer drug development, played a key role in supporting this approval. Pfizer is also exploring global regulatory pathways for BRAFTOVI, with discussions underway with international health authorities.
In the broader context, colorectal cancer remains the third most common cancer worldwide, and BRAF V600E mutations are present in 8-10% of mCRC cases, contributing to a particularly poor prognosis. The BRAF-targeted therapy approved today offers a new avenue for patients with this mutation, providing a first-line option that could significantly improve outcomes for these individuals.
About BRAFTOVI
BRAFTOVI (encorafenib) is an oral kinase inhibitor that targets the BRAF V600E mutation, a driver of cancer growth in certain cancers, including mCRC. The drug is used in combination with cetuximab for patients with BRAF V600E-mutant mCRC, and is not indicated for wild-type BRAF CRC.
