FDA Approves Encorafenib Plus Cetuximab for Metastatic CRC with BRAF V600E Mutation

Thursday, April 09, 2020
The FDA approved the combination use of encorafenib (Braftovi) and cetuximab (Erbitux) for the treatment of adult patients with BRAFV600E-positive metastatic colorectal cancer (mCRC), as detected by an FDA-approved test, after prior therapy, according to Pfizer.1

"BRAF mutations are estimated to occur in up to 15% of people with metastatic colorectal cancer and represent a poor prognosis for these patients,” lead study investigator Scott Kopetz, MD, PhD, FACP, associate professor of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center, said in a press release. “As the first-and-only targeted regimen for people with BRAFV600E-mutant metastatic CRC who have received prior therapy, Braftovi in combination with cetuximab is a much-needed new treatment option for these patients.”

The approval is based on findings from the international open-label phase III BEACON CRC study, which were published in 2019 in the New England Journal of Medicine.2 The trial evaluated encorafenib plus cetuximab with or without binimetinib (Mektovi) in 665 patients with BRAFV600E-positive mCRC whose disease had progressed after 1 or 2 prior regimens.

Patients were randomly assigned in a 1:1:1 ratio to the targeted therapy triplet of encorafenib, binimetinib, and cetuximab; the targeted therapy doublet of encorafenib and cetuximab; or the investigators’ choice of either cetuximab and irinotecan or cetuximab and FOLFIRI (folinic acid, fluorouracil, and irinotecan).

Results showed that the doublet demonstrated an improvement in overall survival (8.4 months [95% CI, 7.5-11.0] vs 5.4 months [95% CI, 4.8-6.6]; HR, 0.60; 95% CI, 0.45-0.79); P = .0003) objective response rates (20.0% [95% CI, 13.0%-29.0%] vs 2.0% [95% CI, 0.0%-7.0%]; P < .0001), and median progression-free survival (4.2 months [95% CI, 3.7-5.4] vs 1.5 months [95% CI, 1.4-1.7]; HR, 0.40; 95% CI, 0.31-0.52; P < .0001), compared with cetuximab plus irinotecan-containing regimens.

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

“We are pleased by the FDA’s approval of Braftovi in combination with cetuximab, as we are committed to developing targeted medicines that can help people living with certain mutation-driven cancers,” Chris Boshoff, MD, PhD, chief development officer of oncology at Pfizer Global Product Development, said in the release. “We are grateful to the patients and study investigators who participated in the phase III BEACON CRC trial and are proud to now be able to offer a targeted treatment option for people with BRAFV600E-mutant metastatic CRC who have received prior therapy. Looking ahead, we’re committed to continuing to investigate this treatment regimen across earlier lines of therapy.”

The FDA previously granted the triplet regimen a breakthrough therapy designation for the treatment of patients with BRAFV600E-mutant mCRC as detected by an FDA-approved test, following failure of 1 or 2 prior lines of treatment. Additionally, the triplet regimen has been included as a category 2A treatment for patients with BRAFV600E-mutant mCRC, following failure of 1 or 2 prior lines of therapy in National Comprehensive Cancer Network guidelines for colon and rectal cancers in the United States.

The ongoing phase II ANCHOR-CRC study (NCT03693170) is investigating the triplet as frontline treatment for patients with BRAFV600E–mutant mCRC.

1. U.S. FDA APPROVES BRAFTOVI® (ENCORAFENIB) IN COMBINATION WITH CETUXIMAB FOR THE TREATMENT OF BRAFV600E-MUTANT METASTATIC COLORECTAL CANCER (CRC) AFTER PRIOR THERAPY. Published April 8, 2020. https://www.pfizer.com/news/press-release/press-release-detail/u_s_fda_approves_braftovi_encorafenib_in_combination_with_cetuximab_for_the_treatment_of_brafv600e_mutant_metastatic_colorectal_cancer_crc_after_prior_therapy. Accessed April 8, 2020.
2. Kopetz S, Grothey A, Yaeger R, et al. Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. N Engl J Med. 2019;381:1632-1643.

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