For patients with advanced BRAF V600-mutant metastatic melanoma, overall survival (OS) is superior with a treatment sequence beginning with nivolumab/ipilimumab (N/I), according to a study presented Nov. 16 at the inaugural American Society of Clinical Oncology Virtual Plenary Series.

Michael B. Atkins, M.D., from the Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C., and colleagues compared the efficacy and toxicity of the sequence of N/I followed by dabrafenib/trametinib (D/T) or the converse sequence for patients with treatment-naive BRAF V600-mutant metastatic melanoma. Patients were randomly assigned to receive step 1 with N/I (arm A; 133 patients) or D/T (arm B; 132 patients) and at disease progression were enrolled in step 2 for alternate therapy: D/T (arm C) or N/I (arm D).

At the fourth interim analysis with 59 percent of patients two years from enrollment, the trial was stopped because the outcomes were definitive enough. The researchers found that at a median follow-up of 27.7 months, 27 and 46 patients had switched to arm C and arm D, respectively. To date, the overall response rates were 46, 43, 48, and 30 percent in arms A, B, C, and D, respectively. Two-year overall survival (OS) was 72 and 52 percent for those starting with arm A and arm B, respectively. Progression-free survival (PFS) showed a trend in favor of arm A. The curves for PFS and OS showed a biphasic pattern, with arm B above arm A until six and 10 months, respectively.

"The drug combinations tested in this trial all improve survival compared to prior standards of care, but we now know which combination should be administered first to achieve maximum benefit for the vast majority of our patients," Atkins said in a statement. "This trial should provide clearer guidance to clinicians on when to administer particular treatments."

Several authors disclosed financial ties to biopharmaceutical companies, including Bristol Myers Squibb, the manufacturer of N/I.

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