FDA Approves Encorafenib and Binimetinib in Combination for Unresectable or Metastatic Melanoma With BRAF Mutations


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On June 27, 2018, the U.S. Food and Drug Administration (FDA) approved the combination of the BRAF inhibitor encorafenib (Braftovi) and the MEK inhibitor binimetinib (Mektovi) in patients with advanced BRAF V600–mutant melanoma, as detected by an FDA-approved test.1 Dual targeting of the MAPK pathway with a BRAF inhibitor plus a MEK inhibitor improves efficacy and ameliorates certain adverse events associated with BRAF inhibitor monotherapy, and such combinations are recommended treatment options for patients with BRAF V600–mutant melanoma, according to investigators. 

Approval was based on the randomized, active-controlled, open-label, multicenter COLUMBUS trial (ClinicalTrials.gov identifier NCT01909453) in 577 patients with BRAF V600E or V600K mutation–positive unresectable or meta-static melanoma. Results of the COLUMBUS trial were published earlier this year and presented at the 2018 ASCO Annual Meeting.1,2 

Study Details and Outcomes

Patients were randomized (1:1:1) to receive binimetinib at 45 mg twice daily plus encorafenib at 450 mg once daily, encorafenib at 300 mg once daily, or vemurafenib (Zelboraf) at 960 mg twice daily. Treatment continued until disease progression or unacceptable toxicity.

The major efficacy measure was progression-free survival using Response Evaluation Criteria in Solid Tumors, version 1.1, and assessed by blinded independent central review. The median progression-free survival was 14.9 months for patients receiving binimetinib plus encorafenib and 7.3 months for the vemurafenib-monotherapy arm (hazard ratio = 0.54, 95% confidence interval = 0.41–0.71, < .0001). Overall response rates assessed by central review were 63% and 40%, respectively. Median response duration was 16.6 months vs 12.3 months, respectively.

Safety and Efficacy

The most common (≥ 25%) adverse reactions in patients receiving the combination were fatigue, nausea, diarrhea, vomiting, abdominal pain, and arthralgia. Discontinuation of therapy due to adverse reactions occurred in 5% of patients receiving the combination; the most common reasons were hemorrhage and headache.

The FDA also granted approval of the THxID BRAF Kit (bioMérieux) as a companion diagnostic for these therapeutics.

The recommended doses are binimetinib at 45 mg orally twice daily and encorafenib at 450 mg orally once daily.

For more information visit FDA.gov. ■

REFERENCES

1. Dummer R, Ascierto PA, Gogas HJ, et al: Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): A multicentre, open-label, randomised phase 3 trial. Lancet Oncol 19:603-615, 2018

2. Dummer R, Ascierto PA, Gogas H, et al: Overall survival in COLUMBUS: A phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in BRAF-mutant melanoma. 2018 ASCO Annual Meeting. Abstract 9504. Presented June 4, 2018.


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