Both drugs received approval in May 2013 as single-agent therapies for patients with metastatic or unresectable melanoma, along with a companion diagnostic test.
The combination treatment is indicated for patients with mutations in the BRAF V600E and V600K genes, the FDA said. Dabrafenib primarily inhibits BRAF V600E, whereas trametinib is a MEK inhibitor that targets both V600E and V600K. About half of melanoma cases have the mutated genes.
The combination therapy was clinically evaluated in a randomized, open-label, phase II clinical trial involving 162 people that compared the two drugs against dabrafenib alone. Among those treated with the two-drug regimen, there was a 78% response rate vs. 54% for single agent treatment. Median response duration was 10.5 months vs. 5.6 months.
The most common side effects included fever, chills, rash, fatigue, nausea, diarrhea, abdominal pain and peripheral edema. More serious adverse reactions included bleeding, blood clots, heart failure, and skin and eye problems. The drug combination can cause infertility and birth defects, the agency said.
An ongoing phase III clinical trial is comparing the dabrafenib-trametinib combination and dabrafenib-placebo as first-line therapy for patients with metastatic or unresectable melanoma.