Global pharma powerhouse Pfizer has announced that the US FDA has granted full approval for BRAFTOVI (encorafenib) in combination with cetuximab (ERBITUX) and fluorouracil-based chemotherapy to treat adults with metastatic colorectal cancer (mCRC) harboring the BRAF V600E mutation.
The decision follows results from the global Phase 3 BREAKWATER trial.
BRAFTOVI in combination with cetuximab and mFOLFOX6 had previously received accelerated approval in December 2024 based on objective response rate (ORR) results. The FDA’s full approval is now backed by substantial evidence showing improved progression-free survival (PFS) and overall survival (OS), alongside ORR data from the trial’s Cohort 3 evaluating BRAFTOVI 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 and Chief US Commercial Officer at 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, 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.”
The BREAKWATER trial confirmed the safety profile of both combination regimens, with no new safety signals identified. Common side effects (≥25%) in the mFOLFOX6 arm included peripheral neuropathy, nausea, fatigue, diarrhea, decreased appetite, rash, vomiting, hemorrhage, abdominal pain, arthralgia, pyrexia, and constipation. In the FOLFIRI arm, frequent side effects included nausea, diarrhea, fatigue, vomiting, alopecia, constipation, abdominal pain, decreased appetite, and rash.
Among patients receiving BRAFTOVI with cetuximab and mFOLFOX6, 14% experienced adverse reactions leading to permanent discontinuation of BRAFTOVI. In the FOLFIRI combination, 9% discontinued permanently due to adverse reactions. Chemotherapy discontinuation rates were comparable across treatment arms.
