- The FDA granted full approval to Pfizer’s (NYSE:PFE) BRAFTOVI + cetuximab + fluorouracil‑based chemotherapy for adults with BRAF V600E‑mutant metastatic colorectal cancer, supported by new survival data from the Phase 3 BREAKWATER trial
- The combination significantly improved progression‑free survival, overall survival, and objective response rates compared with standard chemotherapy regimens
- Safety findings were consistent with known profiles of the individual drugs, with no new safety signals identified across study cohorts
- Pfizer stock (NYSE:PFE) last traded at US$27.10
The U.S. Food and Drug Administration has granted full approval to Pfizer (NYSE:PFE) BRAFTOVI (encorafenib) when used with cetuximab and fluorouracil‑based chemotherapy for adults with metastatic colorectal cancer (mCRC) containing a BRAF V600E mutation.
In a media statement, the pharmaceutical company explained that the decision transitions the therapy from its accelerated approval, issued in December 2024, to full approval based on new survival data from the global Phase 3 BREAKWATER study.
New outcomes data support full approval
The FDA’s action is supported by progression‑free survival (PFS) and overall survival (OS) results from the Phase 3 portion of BREAKWATER, which evaluated BRAFTOVI with cetuximab and mFOLFOX6, along with objective response rate (ORR) data from a separate cohort studying the combination with FOLFIRI.
The updated analysis showed the combination significantly reduced the risk of disease progression or death by 47 per cent compared with chemotherapy with or without bevacizumab. Median PFS increased to 12.8 months versus 7.1 months in the control group. An interim OS analysis demonstrated a 51 per cent reduction in the risk of death, with median OS reaching 30.3 months, double that of the control arm’s 15.1 months.
These results were previously presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the New England Journal of Medicine.
Additional findings from cohort 3
A separate cohort of BREAKWATER evaluated BRAFTOVI with cetuximab and FOLFIRI. That group demonstrated an ORR of 64 per cent compared with 39 per cent in patients receiving FOLFIRI with or without bevacizumab. These findings were presented at the 2026 ASCO Gastrointestinal Cancers Symposium. Additional PFS data from this cohort is expected at a future meeting.
Safety profile
According to trial data, the safety profiles of both treatment regimens remained consistent with known risks associated with the individual agents. No new safety concerns were identified.
Common side effects occurring in at least 25 per cent of patients receiving mFOLFOX6 with the combination included neuropathy, nausea, fatigue, diarrhea, rash, vomiting, and abdominal pain. The most frequent side effects in the FOLFIRI cohort included nausea, diarrhea, fatigue, alopecia, vomiting, and abdominal pain.
Permanent discontinuation of BRAFTOVI due to adverse reactions occurred in 14 per cent of patients treated with the mFOLFOX6 regimen and 9 per cent of those treated with the FOLFIRI regimen.
Context: BRAF V600E-mutant colorectal cancer
Colorectal cancer remains the third most common cancer globally, with an estimated 1.8 million new cases reported in 2022. Approximately 20 per cent of patients present with metastatic disease, and about 8–12 per cent of mCRC cases contain a BRAF mutation, most commonly BRAF V600E. This mutation is associated with poorer clinical outcomes and higher mortality risk.
Prior to the accelerated approval of BRAFTOVI in late 2024, no biomarker‑specific therapies were approved in the U.S. for previously untreated patients with BRAF V600E‑mutant mCRC.
Regulatory status outside the U.S.
The BRAFTOVI combination with mFOLFOX6 is also under regulatory review in Europe, where Pierre Fabre Laboratories holds commercialization rights. The regimen has recently received approvals in other international markets.
About the trial
BREAKWATER is a global, randomized, open‑label Phase 3 trial evaluating BRAFTOVI with cetuximab—alone or combined with fluorouracil‑based chemotherapy—in previously untreated patients with BRAF V600E‑mutant metastatic colorectal cancer. The study includes multiple arms and endpoints, including ORR, PFS, and OS, assessed through blinded independent central review.
Indication
BRAFTOVI is approved for use with cetuximab and fluorouracil‑based chemotherapy specifically for adults with metastatic colorectal cancer harboring a BRAF V600E mutation, as confirmed by an FDA‑authorized test. The therapy is not indicated for patients with wild‑type BRAF tumors.
About Pfizer
Pfizer Inc. is a global biopharmaceutical company that develops and manufactures medicines and vaccines across therapeutic areas including oncology, vaccines, internal medicine, inflammation and immunology, and rare diseases. The company operates in roughly 200 countries, generated $62.6 billion in revenue in 2025, and focuses heavily on advancing a large R&D pipeline aimed at innovative drug development.
Pfizer stock (NYSE:PFE) last traded at US$27.10 and has risen 2.73 per cent since this time next year.
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