FDA Approves Combination Therapy for Advanced BRAF-Mutant Melanoma
The Food and Drug Administration (FDA) has approved Braftovi (encorafenib; Array BioPharma) in combination with Mektovi (binimetinib; Array BioPharma) 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 for the THxID BRAF Kit as a companion diagnostic for these treatments.
The approval of these kinase inhibitors was supported by data from the Phase 3, randomized, active-controlled, open-label, multicenter COLUMBUS trial (N=577). Patients were randomized to receive Braftovi 450mg once daily + Mektovi 45mg twice daily, Braftovi 300mg once daily, or vemurafenib 960mg twice daily.
Results showed that the combination demonstrated a statistically significant improvement in progression-free survival (PFS) compared with vemurafenib (median PFS: 14.9 months vs 7.3 months [hazard ratio (HR) 0.54, 95% CI, 0.41, 0.71; P <.0001], respectively). Moreover, the overall response rates (assessed by a blinded independent central review) were 63% and 40%, respectively; median response duration was 16.6 months for the combination compared with 12.3 months for vemurafenib.
In February 2018, Array BioPharma announced results from the planned analysis of overall survival (OS) data from the COLUMBUS trial which showed that the combination therapy lowered the risk of mortality vs treatment with vemurafenib (HR 0.61, 95% CI, 0.47, 0.79; P <.0001). Patients in the combination group had a median OS of 33.6 months vs 16.9 months for patients in the vemurafenib monotherapy group.
Fatigue, nausea, diarrhea, vomiting, abdominal pain, and arthralgia were the most frequently reported adverse events among patients administered Braftovi + Mektovi.
"Despite recent advances, there remains a significant unmet need for treatments that are both effective and well-tolerated for patients with BRAF-mutant melanoma," said Keith T. Flaherty, M.D., Director of the Termeer Center for Targeted Therapy, Massachusetts General Hospital Cancer Center and Professor of Medicine, Harvard Medical School. "Now, physicians and patients have the option to consider treatment with Braftovi + Mektovi, which has been shown to delay disease progression, improve overall survival and is generally well-tolerated."
Braftovi is available in 50mg and 75mg strength capsules, while Mektovi is supplied as 15mg strength tablets.
For more information visit BraftoviMektovi.com.