- The BRAFTOVI combination regimen is the only approved targeted regimen for first-line BRAF-V600E mutant metastatic colorectal cancer
- Pivotal results from the Phase 3 portion with mFOLFOX6 of the BREAKWATER trial demonstrated a clinically meaningful and statistically significant 51% risk reduction in death and a 47% risk reduction in disease progression or death compared to chemotherapy treatment with or without bevacizumab
- Expanded indication enables flexibility to use BRAFTOVI in combination with cetuximab and different fluorouracil-based chemotherapy regimens
Pfizer Inc. (NYSE: PFE) today announced that the U.S. Food and Drug Administration (FDA) has granted full approval to BRAFTOVI® (encorafenib) in combination with cetuximab (marketed as ERBITUX®) and fluorouracil-based chemotherapy for the treatment of adult patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation based on results from the global Phase 3 BREAKWATER trial (NCT04607421).
BRAFTOVI in combination with cetuximab and mFOLFOX6 was granted accelerated approval by the FDA in December 2024 based on objective response rate (ORR) results, one of the BREAKWATER trial’s dual primary endpoints. The conversion from accelerated approval to full approval is based on significant benefit in outcomes for both progression-free survival (PFS), the trial’s other primary endpoint, and overall survival (OS), a key secondary endpoint, from the Phase 3 portion of the study that evaluated BRAFTOVI in combination with cetuximab and mFOLFOX6, as well as the ORR results from the Cohort 3 portion of the study, which evaluated BRAFTOVI in combination with cetuximab and FOLFIRI.
“This landmark approval, achieved through the robust clinical benefit demonstrated in the BREAKWATER trial, validates that this targeted therapy can impact outcomes for people living with an aggressive, hard-to-treat cancer,” said Aamir Malik, Executive Vice President, Chief U.S. Commercial Officer, Pfizer. “As the only targeted combination regimen shown to deliver a significant improvement in certain outcomes for patients with BRAF V600E‑mutant metastatic colorectal cancer, BRAFTOVI is uniquely positioned to redefine first‑line treatment and establish a new standard of care. This approval reinforces our leadership in bringing differentiated, potentially practice‑changing cancer therapies to patients and healthcare providers who urgently need improved options.”
“This approval gives oncologists confidence to use encorafenib plus cetuximab in combination with fluorouracil-based chemotherapy as a first-line standard of care for patients with BRAF V600E-mutant metastatic colorectal cancer,” 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. “The BREAKWATER study demonstrated that these targeted combination regimens provided statistically significant benefit, providing the robust evidence we need to make treatment decisions that can meaningfully impact patient outcomes.”
In the BREAKWATER study, the safety profile of both combination regimens continued to be consistent with the known safety profile of each respective agent in the regimen. No new safety signals were identified. The most common side effects (≥25%) in the mFOLFOX6 regimen were peripheral neuropathy, nausea, fatigue, diarrhea, decreased appetite, rash, vomiting, hemorrhage, abdominal pain, arthralgia, pyrexia, and constipation. The most common side effects (≥25%) in the FOLFIRI regimen were nausea, diarrhea, fatigue, vomiting, alopecia, constipation, abdominal pain, decreased appetite, and rash.
Among patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6, 14% experienced an adverse reaction that resulted in permanent discontinuation of BRAFTOVI. There was no substantial difference in chemotherapy discontinuation due to side effects in the BRAFTOVI in combination with cetuximab and mFOLFOX6 arm compared with the chemotherapy, with or without bevacizumab arm. Among patients receiving BRAFTOVI in combination with cetuximab and FOLFIRI, 9% experienced an adverse reaction that resulted in permanent discontinuation of BRAFTOVI.
The BRAFTOVI combination regimen with mFOLFOX6 is also under regulatory review in Europe, where Pierre Fabre Laboratories has exclusive commercialization rights, and was recently approved for use in several other countries.
