FDA Approves Cetuximab Plus Encorafenib for Metastatic Colorectal Cancer

Colorectal cancer.

 The FDA has granted approval to cetuximab (Erbitux®, Eli Lilly), in combination with encorafenib (Braftovi®, Array BioPharma) for the treatment of patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation.

“Patients with metastatic colorectal cancer with the BRAF V600E mutation have a poor prognosis, with a median overall survival of 4 to 6 months after failure of initial therapy,” wrote Scott Kopetz, MD, PhD, FACP, Professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, and colleagues, in the publication of their results of the BEACON CRC trial (NCT02928224), on which the FDA approval was based. “Inhibition of BRAF alone has limited activity because of pathway reactivation through epidermal growth factor receptor signaling.”

This open-label phase 3 clinical trial enrolled 665 patients with BRAF V600E–mutated metastatic colorectal cancer who had disease progression after one or two previous treatment regimens. Patients were randomized 1:1:1 to receive encorafenib, binimetinib, and cetuximab; encorafenib and cetuximab; or investigator’s choice of cetuximab/irinotecan or cetuximab/FOLFIRI (folinic acid/fluorouracil/irinotecan). The primary end points were overall survival and objective response rate in the first treatment arm compared with the control group. The secondary end point was overall survival in the second treatment arm compared with the control group.

Cetuximab/encorafenib improved median overall survival compared with the control arm of investigator’s choice (8.4 vs 5.4 months). Patients receiving cetuximab/encorafenib also experienced a higher objective response rate (20% vs 2%) and median progression-free survival (4.2 vs 1.5 months) compared with those receiving investigator’s choice.

The most common adverse events occurring in at least 25% of patients were fatigue, nausea, diarrhea, dermatitis acneiform, abdominal pain, decreased appetite, arthralgia, and rash. The prescribing information for cetuximab includes warnings that infusion reactions, cardiopulmonary arrest, pulmonary toxicity, dermatologic toxicity, hypomagnesemia and accompanying electrolyte abnormalities, and embryo-fetal toxicity may occur.

“This initial analysis in patients with BRAF V600E–mutated metastatic colorectal cancer who had had disease progression after one or two previous regimens showed that a triplet regimen of encorafenib, binimetinib, and cetuximab or a doublet regimen of encorafenib and cetuximab, as compared with current standard therapy, resulted in a significant and clinically relevant benefit with respect to overall survival and objective response rate,” concluded Dr. Kopetz and colleagues in their October 2019 published article in The New England Journal of Medicine.

The recommended dosage of cetuximab, according to the prescribing information, is 100 mg/50 mL (2 mg/mL) or 200 mg/100 mL (2 mg/mL) in a single-dose vial.

For More Information

Kopetz S, Grothey A, Yaeger R, et al (2019). Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. N Engl J Med, 381(17):1632-1643. DOI:10.1056/NEJMoa1908075

Clinicaltrials.gov (2021). Study of encorafenib + cetuximab plus or minus binimetinib vs. irinotecan/cetuximab or infusional 5-fluorouracil (5-FU)/folinic acid (FA)/irinotecan (FOLFIRI)/cetuximab with a safety lead-in of encorafenib + binimetinib + cetuximab in patients with BRAF V600E-mutant metastatic colorectal cancer (BEACON CRC). NLM identifier: NCT02928224.

Erbitux® (cetuximab) prescribing information (2021). Eli Lilly. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125084s279lbl.pdf

Braftovi® (encorafenib) prescribing information (2020). Array BioPharma. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/210496s006lbl.pdf

Eli Lilly (2021). 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. Available at: https://investor.lilly.com/news-releases/news-release-details/fda-expands-lillys-erbituxr-cetuximab-label-combination#:~:text=INDIANAPOLIS%20%2C%20Sept.%2028%2C%202021,for%20the%20treatment%20of%20adult

Image credit: Nephron. Licensed under CC BY-SA 3.0

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