(HealthDay News) — For patients with metastatic melanoma with BRAF V600 mutations, combination therapy with a selective BRAF inhibitor (dabrafenib) and a mitogen-activated protein kinase inhibitor (trametinib) is tolerable and active, according to a study published online Sept. 29 in the New England Journal of Medicine to coincide with presentation at the annual meeting of the European Society for Medical Oncology, held from Sept. 28 to Oct. 2 in Vienna.
Keith T. Flaherty, M.D., from the Massachusetts General Hospital Cancer Center in Boston, and colleagues conducted an open-label phase 1 and 2 study involving 247 patients with metastatic melanoma and BRAF V600 mutations. The pharmacokinetic activity and safety of oral dabrafenib and trametinib was assessed in 85 patients, and 162 patients were randomly allocated to either dabrafenib plus trametinib or dabrafenib monotherapy.
The researchers identified dose-limiting toxic effects infrequently in patients receiving combination therapy (150 mg dabrafenib and 2 mg trametinib [150/2]). Cutaneous squamous cell carcinoma occurred in significantly more patients receiving monotherapy (19 percent) than in those receiving the combination 150/2 (7 percent). Pyrexia was more common in the combination group (71 percent) versus the monotherapy group (26 percent). The median progression-free survival was 9.4 months in the combination group versus 5.8 months in the monotherapy group (hazard ratio for progression or death, 0.39). The rate of complete or partial response was significantly higher in the combination versus the monotherapy group (76 versus 54 percent; P = 0.03).
“Dabrafenib and trametinib were safely combined at full monotherapy doses,” the authors write. “We believe that the combination of dabrafenib and trametinib warrants further evaluation as a potential treatment for metastatic melanoma with BRAF V600 mutations and other cancers with these mutations.”
Several authors are employees of GlaxoSmithKline, which funded the study and manufactures dabrafenib and trametinib.