Real-World Efficacy and Safety of MEK Inhibitor for Patients With Advanced NRAS-Mutant Melanoma: A Single-Center Retrospective Study in Japan.

NRAS mutations represent the second most common genetic alteration in melanoma and are associated with aggressive disease and limited treatment options. While MEK inhibitors have shown clinical benefit in patients with NRAS-mutant melanoma in clinical trials, real-world data in Asian populations remain limited. We conducted a retrospective analysis of patients with advanced NRAS-mutant melanoma treated with binimetinib at the National Cancer Center Hospital. NRAS mutations were confirmed via comprehensive genomic profiling. Fifteen patients were included, with a median age of 66 years. Most had mucosal melanoma (80.0%), and NRAS mutations at codons 12, 13, and 61 were seen in seven, one, and seven patients, respectively. One patient (6.7%) achieved a partial response, and eight (53.3%) had stable disease, resulting in a disease control rate of 60.0%. The median PFS was 3.1 months (95% confidence intervals, 1.5-4.6), and the median OS was 4.8 months (95% confidence intervals, 1.8-8.8). Fourteen patients (93.3%) experienced at least one adverse event (AE), with skin rash being the most common. Grade ≥ 3 AEs occurred in 4 patients (26.7%), and 8 (53.5%) required dose interruption. Binimetinib demonstrated modest clinical activity and manageable safety in Japanese patients with advanced NRAS-mutant melanoma, with outcomes comparable to those observed in Western populations. This study is limited by its retrospective design and small sample size, warranting cautious interpretation of results. These findings provide supportive evidence for the use of binimetinib in patients with NRAS-mutant melanoma following immune checkpoint inhibitor failure.