Priority Review to Combination for Melanoma

http://journals.lww.com/oncology-times/Fulltext/2015/08250/New_Cancer_Related_FDA_Actions.15.aspx

The FDA also gave Priority Review status to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

The drugs are oral agents used to block signaling in different sites of the same molecular pathway that promotes cancer cell growth—Tafinlar is a BRAF inhibitor and Mekinist is a MEK inhibitor.

Tafinlar and Mekinist were each already approved in 2013 as single agents (OT 6/25/13 issue); and the drug combination therapy was approved last year under the FDA's Accelerated Approval program (OT 2/10/14 issue). That approval, though, was contingent on the results of the COMBI-d study, which was designed to evaluate the clinical benefit of the Tafinlar/Mekinist combination therapy in patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

The FDA's priority review designation shortens the time to complete a drug's review and aims to deliver a decision on marketing approval designation for drugs that may offer major advances in treatment or provide a treatment where no adequate therapy exists within six months under the Prescription Drug User Fee Act (PDUFA). The FDA action date for the drug combination is November 2015.

The double-blinded, Phase III COMBI-d study included 423 patients with unresectable or metastatic BRAF V600E/K mutation-positive cutaneous melanoma, who were randomized to receive the Tafinlar/Mekinist combination or therapy with Tafinlar and placebo. The updated results showed that patients receiving the Tafinlar/Mekinist combination had a median survival of 25.1 months compared with 18.7 months for patients receiving Tafinlar and placebo.

Seventy four percent of patients receiving Tafinlar and Mekinist were alive after one year of receiving the combination and 51 percent of the patients in that study arm were alive at two years, compared with 68 percent and 42 percent respectively for patients in the Tafinlar/placebo arm.

The safety results were consistent with the profile observed to date for the combination and consistent with the profile observed for Tafinlar monotherapy; no new safety concerns were observed. The most common adverse events for patients receiving the Tafinlar/Mekinist combination were pyrexia, fatigue, nausea, headache, chills, diarrhea, rash, arthralgia, hypertension, vomiting, cough, and peripheral edema.

There was a lower incidence of cutaneous squamous cell carcinoma including keratoacanthoma with the Tafinlar/Mekinist arm (3%) compared with the Tafinlar/placebo arm (10%). Eleven percent of patients in the Tafinlar/Mekinist arm had to discontinue treatment due to adverse events compared with seven percent of patients receiving Tafinlar/placebo.

Both Tafinlar and Mekinist are marketed by Novartis.