FDA approves combo treatment for melanoma

Aug 06, 2018, 9:35am

Combination that extends survival in BRAF-mutant metastatic melanoma gains FDA approval.

The combination of encorafenib and binimetinib (Braftovi and Mektovi) has been granted approval by the U.S. Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test. The FDA also granted approval to THxID BRAF Kit (bioMérieux) as a companion diagnostic for these therapeutics.

The combination of encorafenib and binimetinib has been shown to delay disease progression and improve overall survival (OS), and is generally well tolerated. Aproval was based on results from the COLUMBUS trial, a randomized, active-controlled, open-label, multicenter trial that included in 577 patients with BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma. Patients were randomized to binimetinib 45 mg twice daily plus encorafenib 450 mg once daily, encorafenib 300 mg once daily, or vemurafenib 960 mg twice daily. Treatment continued until disease progression or unacceptable toxicity.

The median progression-free survival using RECIST 1.1 response criteria, the primary efficacy outcome was 14.9 months for patients randomized to binimetinib plus encorafenib versus 7.3 months for the vemurafenib monotherapy arm (HR 0.54, 95% CI 0.41-0.71, P<0.0001). Overall response rates assessed by central review were 63% and 40%, respectively. Median response duration was 16.6 months vs. 12.3 months, respectively.

The most common (≥25%) adverse reactions in patients receiving the combination were fatigue, nausea, diarrhea, vomiting, abdominal pain, and arthralgia. Five percent of patients who received the combination discontinued therapy due to adverse reactions, with the most common reasons being hemorrhage and headache.

An OS analysis released in February 2018 revealed a 39% reduction in the risk of death in patients who received the combination compared with vemurafenib (HR 0.61, 95% CI 0.47-0.79, P<0.0001). Patients randomized to the combination had a median OS of 33.6 months compared with 16.9 months for those randomized to vemurafenib monotherapy.

BRAF is the most common genetic mutation in metastatic melanoma. According to Valerie Guild, Co-Founder and President of the AIM at Melanoma Foundation, nearly half of patients diagnosed with metastatic melanoma test positive for the BRAFmutation.