Efficacy of Nivolumab and Ipilimumab Combined Therapy as a First-Line Therapy for Patients with Advanced Melanoma and the Urgent Need for an Effective Second-Line Therapy for Patients with Wild-Type BRAF in Japan: A Single Center Retrospective Study.

Therapeutic advantages of immune checkpoint inhibitors, anti-programmed death-1 (PD-1), and anticytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) in melanoma have been reported recently. In this study, we conducted a retrospective study to evaluate the clinical efficacy and safety of the combined use of nivolumab and ipilimumab as a first-line therapy for Japanese patients with advanced melanoma. Moreover, we examined the effects of second-line treatment. Seven patients were enrolled in this study. The median progression-free survival (PFS) and median overall survival (OS) were 7 months (95%CI, 1.868-12.132) and 12 months (95%CI, 0.000- 27.397), respectively. The objective response rate (ORR) and the disease control rate (DCR) were 42.9 % and 85.7 %. Three patients chose pembrolizumab monotherapy as second-line therapy after the combination therapy due to their BRAF wild-type status, which resulted in progressive disease. ORR and DCR were 0% and 33.3%, respectively, with pembrolizumab. Grade 3 or 4 immune-related adverse events occurred in 71.4% of the patients treated with the combined-therapy. All irAEs were treated with corticosteroid or hormone replacement therapy. Although this single center retrospective study had some limitations, it demonstrated good efficacy for the combined use of nivolumab and ipilimumab as a first-line therapy for Japanese patients with advanced melanoma. Moreover, poor efficacy was observed for the second-line therapy after the combined therapy. These findings suggest that a novel second-line therapy is required for patients with advanced melanoma in Japan, particularly for patients with wildtype BRAF.