FDA approves Tafinlar (dabrafenib) + Mekinist (trametinib) for BRAF V600E/K metastatic melanoma- Novartis

The FDA has granted regular approval for the combination of Tafinlar (dabrafenib) + Mekinist (trametinib), from Novartis, for the treatment of patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma as detected by an FDA-approved test. This is the first targeted therapy combination demonstrating more than two years overall survival in patients with the most aggressive form of skin cancer.

Approval is based on survival data from two Phase III studies: COMBI-d and COMBI-v. These studies showed that dabrafenib + trametinib demonstrated statistically significant progression-free survival (PFS) and overall survival (OS) compared with dabrafenib or vemurafenib monotherapy, in patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma. Updated results from the COMBI-d study showed that the combination achieved a statistically significant OS benefit compared to dabrafenib monotherapy (median of 25.1 months vs 18.7 months). The combination also showed median PFS of 9.3 months compared to 8.8 months for those who received dabrafenib only. For COMBI-v, median PFS was 11.4 months vs 7.3 months for the dabrafenib + trametinib arm compared to the vemurafenib arm. ORR was 64% in the combination arm and 51% in the vemurafenib arm and median DoR was 13.8 months for the combination and 7.5 months in the vemurafenib arm.

Comment: The FDA granted priority review in July 2015 for approval of the dabrafenib + trametinib combination in BRAF V600E/K mutation-positive unresectable or metastatic melanoma. Since January 2014, the combination has been approved for use in the US in patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma as detected by an FDA-approved test. The combination was initially approved based on Phase II data through the FDA’s Accelerated Approval program and reviewed under a priority review designation. The approval was contingent on the results of the Phase III COMBI-d study, which was designed to evaluate the clinical benefit of the combination in patients with unresectable or metastatic melanoma with a BRAF V600E/K mutation.