FDA Expands Cetuximab Label With Combination of Encorafenib for Pretreated BRAF V600E Mutation–Positive Metastatic Colorectal Cancer

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The U.S. Food and Drug Administration (FDA) has granted approval of a new indication for cetuximab (Erbitux) in combination with encorafenib (Braftovi) for the treatment of adult patients with metastatic colorectal cancer and a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy. 


The safety of cetuximab (400 mg/m2 initial infusion, followed by 250 mg/m2 weekly) in combination with encorafenib (300 mg once daily) was evaluated in a randomized, open-label, active-controlled trial (BEACON CRC).

Eligible patients had BRAF V600E–mutant metastatic colorectal cancer, as detected by an FDA-approved test, with disease progression after one or two prior regimens. Patients were randomly assigned 1:1:1 to one of the following treatment arms:

  • Encorafenib at 300 mg orally once daily in combination with cetuximab
  • Encorafenib at 300 mg orally once daily in combination with cetuximab and binimetinib
  • Irinotecan with cetuximab or FOLFIRI (leucovorin, fluorouracil, irinotecan) with cetuximab.

The major efficacy outcome measure was overall survival. Additional efficacy outcome measures included progression-free survival, objective response rate, and duration of response as assessed by blinded independent central review. Overall and progression-free survival were assessed in all randomly assigned patient; objective response rate and duration of response were assessed in the subset of the first 220 patients included in the randomized portion of the encorafenib/cetuximab and control arm of the study.

A total of 220 patients were randomly assigned to the encorafenib/cetuximab arm and 221 to the control arm. The trial was conducted at over 200 investigational sites in North America, South America, Europe, and the Asia-Pacific region.

In BEACON CRC, cetuximab plus encorafenib showed a median overall survival of 8.4 months (95% confidence interval [CI] = 7.5–11.0), compared to 5.4 months (95% CI = 4.8–6.6) in the control arm (irinotecan with cetuximab or FOLFIRI with cetuximab, hazard ratio [HR] = 0.60, 95% CI = 0.45–0.79, P = .0003). Additionally, cetuximab plus encorafenib showed an objective response rate of 20% (95% CI = 13%–29%) compared to 2% (95% CI = 0%–7%) for the control arm (P < .0001), and a median progression-free survival of 4.2 months (95% CI = 3.7–5.4) compared to 1.5 months for the control arm (95% CI = 1.4–1.7; HR = 0.40, 95% CI = 0.31–0.52, P < .0001).

The most common (≥ 25%) adverse reactions in patients receiving cetuximab in combination with encorafenib were fatigue, nausea, diarrhea, dermatitis acneiform, abdominal pain, decreased appetite, arthralgia, and rash.

The labeling for cetuximab includes warnings and precautions for infusion reactions, cardiopulmonary arrest, pulmonary toxicity, dermatologic toxicity, hypomagnesemia and accompanying electrolyte abnormalities, and embryofetal toxicity.


The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.