FDA Alert

FDA Grants Traditional Approval to Encorafenib (Braftovi) for BRAF V600E–Mutant Metastatic Colorectal Cancer

Edited by:
Anthony Calabro, MA

Key Highlights

  • The FDA approved encorafenib plus cetuximab and fluorouracil-based chemotherapy for BRAF V600E–mutant metastatic colorectal cancer.
  • The BREAKWATER trial demonstrated improved PFS and OS vs standard chemotherapy.
  • ORR was significantly higher with encorafenib-based combinations.
  • The recommended dose is 300 mg orally once daily in combination therapy until there is disease progression or unacceptable toxicity.

On February 24, 2026, the FDA granted traditional approval to Braftovi (encorafenib) in combination with cetuximab and fluorouracil-based chemotherapy for the treatment of adult patients with metastatic colorectal cancer (mCRC) harboring a BRAF V600E mutation, as detected by an FDA-authorized test. Encorafenib previously received accelerated approval in 2024 in combination with cetuximab and mFOLFOX6 for metastatic CRC with a BRAF V600E mutation.

Approval was based on results from the phase 3 BREAKWATER trial, a randomized, active-controlled, open-label, multicenter study in treatment-naïve patients with BRAF V600E mutation–positive metastatic CRC identified using the Qiagen therascreen BRAF V600E RGQ PCR Kit. In the phase 3 portion, 236 patients were randomized to encorafenib plus cetuximab and mFOLFOX6 (Arm B) and 243 to control chemotherapy (Arm C). Median PFS was 12.8 months (95% CI, 11.2–15.9) vs 7.1 months (95% CI, 6.8–8.5), respectively (HR, 0.53; 95% CI, 0.41–0.68; P < .0001). Median OS was 30.3 months (95% CI, 21.7 to not estimable) vs 15.1 months (95% CI, 13.7–17.7) (HR, 0.49; 95% CI, 0.38–0.63; P < .0001). ORR was 61% (95% CI, 52%–70%) vs 40% (95% CI, 31%–49%) (P = .0008).

In Cohort 3 of BREAKWATER, 73 patients were randomized to encorafenib plus cetuximab and FOLFIRI (Arm D) and 74 to control (Arm E). The ORR was 64% (95% CI, 53%–74%) vs 39% (95% CI, 29%–51%), respectively (P = .0011).

The prescribing information includes warnings and precautions for new primary malignancies (cutaneous and noncutaneous), tumor promotion in BRAF–wild-type tumors, cardiomyopathy, hepatotoxicity, hemorrhage, uveitis, QT prolongation, and embryo-fetal toxicity.

The recommended encorafenib dose is 300 mg (4 of the 75-mg capsules) orally once daily in combination with cetuximab and mFOLFOX6 or with cetuximab and FOLFIRI. Treatment should continue until disease progression or unacceptable toxicity.

Reference
U.S. Food and Drug Administration. FDA grants traditional approval to encorafenib for metastatic colorectal cancer with a BRAF V600E mutation. FDA. Published February 24, 2026. Accessed February 24, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-encorafenib-metastatic-colorectal-cancer-braf-v600e-mutation