For patients with treatment-naive BRAFv600 mutant metastatic melanoma, treatment first with combination nivolumab/ipilimumab yields better overall survival than dual BRAF/MEK inhibition with dabrafenib/trametinib, according to a study published online Sept. 27 in the Journal of Clinical Oncology .

Michael B. Atkins, M.D., from the Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C., and colleagues examined the optimal treatment sequence between combination nivolumab/ipilimumab checkpoint inhibitor immunotherapy and combination dabrafenib/trametinib molecularly targeted therapy for patients with treatment-naive BRAFv600 mutant metastatic melanoma. A total of 265 patients were randomly assigned to receive combination nivolumab/ipilimumab (arm A) or dabrafenib/trametinib (arm B) in step 1, and 73 received alternative therapy in step 2: dabrafenib/trametinib (arm C) or nivolumab/ipilimumab (arm D; 27 and 46 patients, respectively).

Due to achievement of a clinically significant end point, the study was stopped early. The researchers found that two-year overall survival was 71.8 and 51.5 percent for those starting in arm A and arm B, respectively. Step 1 progression-free survival favored arm A. The objective response rates were 46.0, 43.0, 47.8, and 29.6 percent for arms A, B, C, and D, respectively. The median duration of response was not reached in arm A and was 12.7 months in arm B. In 52 percent of patients with documented disease progression, crossover occurred.

"Combination immunotherapy, in contrast to targeted therapy, produces more long-lasting tumor shrinkage, reduces the risk of disease progression in the central nervous system, and doesn't interfere with the subsequent effectiveness of the alternative treatment approach," Atkins said in a statement.

Bristol Myers Squibb and Novartis provided the study medications.

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