A pooled analysis of four clinical trials of nivolumab (Opdivo) in advanced melanoma, reported by Larkin et al in JAMA Oncology, suggested similar response rates in patients with BRAF V600–mutant and BRAF wild-type disease.
The retrospective analysis included data from adult patients with unresectable stage III or stage IV melanoma from four clinical trials. Nivolumab was given at 0.1, 0.3, 1.0, 3.0, or 10.0 mg/kg every 2 weeks until disease progression, treatment discontinuation due to adverse events, withdrawal, or end of study, with 83% of patients receiving the 3 mg/kg dose. Overall, 72% of patients in the BRAF-mutant group had received prior BRAF inhibitor therapy. A total of 73% of patients in the BRAF wild-type group and 86% in the mutant group had received at least two prior therapies for advanced disease.
Among patients evaluable for objective response, response rates were 34.6% (95% confidence interval [CI] = 28.3%–41.3%) among 217 patients with wild-type BRAF and 29.7% (95% CI = 19.7%–41.5%) among 74 with BRAF-mutant status. Objective response rates did not seem to be affected by prior BRAF inhibitor therapy (35% vs 29% among those with no prior therapy; 30% in BRAF-mutant patients with prior therapy), prior ipilimumab (Yervoy) therapy (36% vs 25% among those with prior therapy; 31% vs 39% among those without prior therapy), or tumor PD-L1 (programmed death ligand 1) status (54% vs 33% among PD-L1–positive patients; 22% vs 27% among PD-L1–negative/indeterminate patients). The median duration of response was 14.8 months (95% CI = 11.1–24.0 months) in the wild-type BRAF group and 11.2 months (95% CI = 7.3–22.9 months) in the BRAF-mutant group, with a median time to response being 2.2 months in both groups.
The most common treatment-related adverse events of any grade among the total of 334 wild-type BRAF patients and 106 BRAF-mutant patients were fatigue (26% vs 17%), pruritus (17% vs 9%), rash (12% vs 10%), and diarrhea (12% vs 8%). Treatment-related grade 3 or 4 adverse events occurred in 11.7% vs 2.8%, with none occurring in more than two patients in either group. Adverse events led to discontinuation of treatment in 6% vs 11%, respectively.
The investigators concluded, “The results of this retrospective analysis suggest that nivolumab has similar efficacy and safety outcomes in patients with wild-type or mutant BRAF, regardless of prior BRAF inhibitor or ipilimumab treatment.”
James Larkin, MD, PhD, of Royal Marsden Hospital, is the corresponding author of the JAMA Oncology article.
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