Targeted therapy has officially entered the first-line standard of care for a high-risk molecular subset of metastatic colorectal cancer (mCRC).
Pfizer Inc. announced that the U.S. FDA granted full approval to BRAFTOVI (encorafenib) in combination with ERBITUX (cetuximab) and fluorouracil-based chemotherapy for adults with BRAF V600E–mutant metastatic colorectal cancer.
This marks the first fully approved biomarker-driven targeted regimen in the first-line setting for this aggressive CRC subtype.
What Changed: From Accelerated to Full Approval
The combination previously received accelerated approval in December 2024 based on response rate data. Full approval is supported by Phase 3 results from the BREAKWATER trial, demonstrating significant improvements in:
- Overall Survival (OS)
- Progression-Free Survival (PFS)
- Objective Response Rate (ORR)
Key Clinical Data (BREAKWATER Trial)
BRAFTOVI + Cetuximab + mFOLFOX6
Compared to chemotherapy ± bevacizumab:
- 51% reduction in risk of death (HR 0.49)
- Median OS doubled: 30.3 months vs 15.1 months
- 47% reduction in risk of progression or death (HR 0.53)
- Median PFS: 12.8 months vs 7.1 months
These results were presented at ASCO 2025 and published in the New England Journal of Medicine.