FDA OKs Combo Adjuvant Therapy for BRAF V600-Mutant Melanoma

Trametinib plus dabrafenib is the first oral targeted adjuvant combination therapy to demonstrate significant clinical benefit in patients with a BRAF V600 mutation, following complete surgical resection.

Officials with the FDA approved dabrafenib (Tafinlar, Novartis) in combination with trametinib (Mekinist) for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, according to a press release.

Dabrafenib plus trametinib is the first oral targeted adjuvant combination therapy to demonstrate significant clinical benefit in patients with a BRAF V600 mutation following complete surgical resection. The FDA previously granted the combination breakthrough therapy designation for this indication in October 2017 and granted priority review in December 2017.

The approval is based on data from the COMBI-AD phase 3 study, which included 870 patients with stage 3 BRAF V600E/K mutation-positive melanoma treated with the combination therapy after complete surgical resection. In the trial, patients were treated for 12 months and stratified based on BRAF mutation and stage.

According to the data, patients who received the dabrafenib (150 mg BID) plus trametinib (2 mg QD) combination had a reduced risk of disease recurrence or death compared with those who received the placebo by 53%.

“The purpose of adjuvant therapy is to improve recurrence-free and overall survival in our patients with melanoma,” John M. Kirkwood, MD, Usher Professor of Medicine, director of melanoma and skin cancer at the University of Pittsburgh, said in the press release. “Adjuvant therapy options are crucial today because more than half of patients have a recurrence after surgery.”

Improvements were also observed in key secondary endpoints, including overall survival, distant metastasis-free survival, and freedom from relapse.

Adverse events were consistent with other studies evaluating dabrafenib plus trametinib and no new safety signals were reported.

The combination therapy is also approved in the United States for the treatment of BRAF V600E mutation-positive non-small cell lung cancer.

Reference

Novartis receives FDA approval of Tafinlar® + Mekinist® for adjuvant treatment of BRAF V600-mutant melanoma [news release]. Novartis’ website. https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-tafinlarr-mekinistr-adjuvant-treatment-braf-v600-mutant-melanoma