The Food and Drug Administration has granted regular approval for the combination of Tafinlar (dabrafenib) plus Mekinist (trametinib) for the treatment of patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma as detected by an FDA-approved test. The drugs are oral agents used to block signaling in different sites of the same molecular pathway that promotes cancer cell growth.
The combination was previously approved through the FDA's Accelerated Approval program, which allows the FDA to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients (OT 2/10/15 issue). The accelerated approval was contingent on the results of the Phase III COMBI-d study, which was designed to evaluate the clinical benefit of the combination therapy in patients with unresectable or metastatic melanoma with a BRAF V600E/K mutation, upon which this most recent approval is based.
The COMBI-d study randomized 423 patients with unresectable or metastatic BRAF V600E/K mutation-positive cutaneous melanoma to receive the Tafinlar plus Mekinist combination or Tafinlar plus placebo. Patients receiving the Tafinlar plus Mekinist combination had a median overall survival of 25.1 months compared with 18.7 months for the patients receiving Tafinlar plus placebo. Progression-free survival was 9.3 months for patients receiving Tafinlar plus Mekinist compared with 8.8 months for the patients receiving Tafinlar plus placebo.
Data from the COMBI-d study and previous studies show the most common adverse events for Tafinlar plus Mekinist were pyrexia, nausea, rash, chills, diarrhea, headache, vomiting, hypertension, arthralgia, peripheral edema, and cough. The most common grade 3/4 adverse reactions were hypertension, pyrexia, and hemorrhage.
Clinical Quick Facts
Drug: Tafinlar (dabrafenib)+Mekinist (trametinib) combination
Approved Indication: Treatment of patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma as detected by an FDA-approved test
Serious Side Effects: Hypertension, pyrexia, and hemorrhage
Common Side Effects: Pyrexia, nausea, rash, chills, diarrhea, headache, vomiting, hypertension, arthralgia, peripheral edema, and cough