FDA Approves New Melanoma Indication for Tafinlar–Mekinist Combination

Treatment benefits certain patients with BRAF V600-mutant disease

The FDA has approved dabrafenib (Tafinlar) in combination with trametinib (Mekinist), both Novartis products, for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutation, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection. The FDA granted the combination breakthrough therapy designation for this indication in October 2017 and priority review in December 2017.

The approval is based on results from COMBI-AD, a phase 3 study of 870 patients with stage III BRAF V600E/K mutation-positive melanoma treated with dabrafenib plus trametinib after complete surgical resection. Patients received the dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) combination (n = 438) or matching placebos (n = 432).

After a median follow-up of 2.8 years, the primary endpoint of relapse-free survival (RFS) was met. Treatment with the combination therapy significantly reduced the risk of disease recurrence or death by 53% compared with placebo. The RFS benefit among the combination arm was observed across all patient subgroups, including disease substage. Improvements were also observed in key secondary endpoints including overall survival (OS), distant metastasis-free survival (DMFS), and freedom from relapse (FFR). These results were published in the New England Journal of Medicine in October 2017.

Adverse events (AEs) were consistent with other dabrafenib-plus-trametinib studies, and no new safety signals were reported. Of patients treated with the combination, 97% experienced an AE, 41% had grade 3/4 AEs, and 26% had AEs leading to treatment discontinuation (versus 88%, 14%, and 3%, respectively, with placebo).

In the U.S., dabrafenib in combination with trametinib is approved for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or K mutations, as detected by an FDA-approved test, and for the adjuvant treatment of melanoma with BRAF V600E or K mutations and involvement of lymph node(s) following complete resection. Dabrafenib plus trametinib is also approved for BRAF V600E mutation-positive non–small-cell lung cancer.

Source: Novartis; April 30, 2018.