Dabrafenib is a selective BRAF inhibitor and trametinib is a selective MAPK kinase (MEK) inhibitor. The drugs can be used alone or in combination for the treatment of metastatic melanoma with BRAF V600 mutations. Results of a new study show that, when used in combination, progression-free survival (PFS) significantly improved.
A multi-center team from around the United States evaluated 247 patients with metastatic melanoma and BRAF V600 mutations. The pharmacokinetic activity and safety of oral dabrafenib (75 or 150 mg twice daily) and trametinib (1, 1.5, or 2 mg daily) was evaluated in 85 patients; 162 patients were then randomly assigned to receive combination therapy with dabrafenib (150 mg) plus trametinib (1 or 2 mg) or dabrafenib monotherapy. Primary end points were the incidence of cutaneous squamous-cell carcinoma, survival free of melanoma progression, and response, and the secondary endpoints were overall survival and pharmacokinetic activity, according to the results of the study that were published in the New England Journal of Medicine (NEJM).
Dose-limiting toxic effects were infrequent, according to the researchers. In regard to adverse events, cutaneous squamous cell carcinoma was seen in 7% of patients receiving combination therapy and in 19% of patients receiving monotherapy (P=0.09), while pyrexia was more common in the combination group than in the monotherapy group (71% vs. 26%).
Median PFS in the combination group was 9.4 months, compared to 5.8 months in the monotherapy group (hazard ratio for progression or death, 0.39; 95% confidence interval, 0.25 to 0.62; P<0.001). The rate of complete or partial response with combination therapy was 76%, compared to 54% with monotherapy (P=0.03), the researchers report in NEJM.
