FDA Approves Cetuximab Indication in Combination With Encorafenib to Treat Metastatic CRC Subtype

Cetuximab represents the first approved anti-EGFR antibody which, in combination with encorafenib, is now available to treat adults with pretreated metastatic CRC with a BRAF V600E mutation.

The FDA has approved an indication for cetuximab (Erbitux) in combination with encorafenib (Braftovi) to treat BRAF V600E mutation-positive metastatic colorectal cancer (mCRC) following prior therapy, according to Eli Lilly.1

Notably, cetuximab is now the first anti-EGFR antibody approved to treat mCRC with a BRAF V600E mutation, in combination with encorafenib. Encorafenib was approved by the FDA on this indication, based on data from the BEACON CRC study, in April 2020.

The regulatory decision for the cetuximab indication is also based on findings from the randomized, open-label, multicenter, BEACON CRC trial (NCT02928224). Eligible participants included patients with BRAF V600E mutation-positive mCRC, as detected by the Qiagen therascreen® BRAF V600E RGQ PCR kit, whose disease has progressed beyond 1 or 2 prior therapies.2

"The BEACON study showed that the combination of [cetuximab] 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, oncology, Lilly, stated in a press release. "We are grateful to Pfizer for their collaboration as we've worked to bring this treatment regimen to patients."

In the trial, patients treated with the combination experienced a median overall survival (OS) of 8.4 months (95% CI, 7.5-11.0), compared with 5.4 months in the control arm (HR, 0.60; 95% CI, 0.45-0.79; P = .0003). In addition, patients treated with the experimental regimen demonstrated an objective response rate (ORR) of 20% (95% CI, 13%-29%), compared to 2% (95% CI, 0%-7%) for the control arm (P = .0001).

The median progression-free survival (mPFS) among patients treated with cetuximab plus encorafenib was 4.2 months (95% CI, 3.7-5.4), compared with 1.5 months for those treated with the control combinations (95 % CI, 1.4-1.7; HR, 0.40; 95% CI, 0.31-0.52; P < .0001). The median duration of response (DoR) was 6.1 months (95% CI, 4.1-8.3) for patients treated with encorafenib and cetuximab, and was not reached among the control group (95% CI, 2.6 to not reached [NR]).

Observed adverse events (AEs) that affected over 25% of participants included fatigue, nausea, diarrhea, dermatitis acneiform, abdominal pain, decreased appetite, arthralgia, and rash.

The label for cetuximab offers a warning about infusion reactions, cardiopulmonary arrest, pulmonary toxicity, dermatologic toxicity, hypomagnesemia and accompanying electrolyte abnormalities, and embryo-fetal toxicity.


  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 and Company. September 29, 2021. Accessed September 29, 2021. https://bit.ly/3unDhlk
  2. US FDA approves BRAFTOVI (encorafenib) in combination with cetuximab for the treatment of BRAFV600E-mutant metastatic colorectal cancer (CRC) after prior therapy. April 8, 2020. Accessed September 29, 2021. https://bit.ly/34opTAr