FDA Expands Label for Cetuximab Plus Encorafenib for BRAF V600E+ Metastatic Colorectal Cancer Following Prior Therapy

The FDA has expanded the label for cetuximab/encorafenib for the treatment of patients with previously treated BRAF V600E–positive metastatic colorectal cancer.

The label for cetuximab (Erbitux) and encorafenib (Braftovi) has expanded for adult patients with previously treated metastatic colorectal cancer (CRC) with a BRAF V600E mutation detected through an FDA-approved test, according to a press release from drug developer Eli Lilly.1

The indication is based on findings from the phase 3 BEACON CRC trial (NCT02928224), which demonstrated the benefit of the combination in patients with previously treated BRAF V600E–mutant disease.2 Data from the trial indicated that patients who received the combination achieved a median overall survival (OS) of 8.4 months (95% CI, 7.5-11.0) vs 5.4 months (95% CI, 4.8-6.6) in the control group (P < .0001), which consisted of treatment with irinotecan plus cetuximab or leucovorin calcium, fluorouracil, and irinotecan plus cetuximab.

The expansion marks the seventh FDA approval of cetuximab for certain types of CRC and head and neck squamous cell carcinoma.

“The BEACON study showed that the combination of Erbitux and encorafenib significantly improved overall survival in patients with metastatic colorectal cancer with a BRAF V600E mutation – a subtype that typically has worse outcomes compared to those without the mutation,” David Hyman, MD, chief medical officer of oncology at Eli Lilly. “We are grateful to Pfizer for their collaboration as we've worked to bring this treatment regimen to patients.”

An initial 400 mg/m2 intravenous dose of cetuximab followed by 250 mg/m2 weekly plus a 300 mg dose of encorafenib daily was administered to 216 patients on the randomized, open label trial

The experimental combination also yielded an objective response rate of 20% (95% CI, 13%-29%) compared with 2% (95% CI, 4.8%-6.6%) among those in the control arm (HR, 0.60; 95% CI, 0.45-0.79; P = .0003). Additional findings from the study indicated patients who received cetuximab plus encorafenib experienced a median progression-free survival of 4.2 months (95% CI, 3.7-5.4) vs 1.5 months in the control group (95% CI, 1.4-1.7; HR, 0.40; 95% CI, 0.31-0.52; P <.0001).

The most common adverse events from receiving cetuximab were fatigue, nausea, diarrhea, dermatitis acneiform, abdominal pain, decreased appetite, arthralgia, and rash. Additionally, warnings have been issued for toxicities such as infusion reactions, cardiopulmonary arrest, pulmonary toxicity, dermatologic toxicity, hypomagnesemia and accompanying electrolyte abnormalities, and embryo-fetal toxicity.

The FDA previously approved the use of encorafenib plus cetuximab for patients with BRAF V600E–mutant CRC in April 2020.


  1. FDA expands Lilly's ERBITUX® (cetuximab) label with combination of BRAFTOVI® (encorafenib) for the treatment of BRAF V600E mutation-positive metastatic colorectal cancer (CRC) after prior therapy. News release. Eli Lilly. September 28, 2021. Accessed September 29, 2021. https://bit.ly/3ied9nV
  2. Tabernero J, Grothey A, Cutsem EV, et al. Encorafenib plus cetuximab as a new standard of care for previously treated BRAF V600E-mutant metastatic colorectal cancer: updated survival results and subgroup analyses from the BEACON study. J Clin Oncol. 2021;39(4):273-284. doi:10.1200/JCO.20.02088
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