Recent advances in therapeutic strategies for unresectable or metastatic melanoma and real-world data in Japan.

New therapeutic strategies including immunotherapy and selective molecular target inhibitors have brought about a new era in the treatment of patients with advanced melanoma. In Japan, the immune checkpoint inhibitors ipilimumab, nivolumab and pembrolizumab, the BRAF inhibitor (BRAFi) vemurafenib, dabrafenib and MEK inhibitor (MEKi) trametinib have been available for the treatment of unresectable and metastatic melanoma. The BRAFi + MEKi combination shows high response rates (60-70%) and rapid response induction associated with symptom control, with a progression-free survival of 12 months. Nivolumab and pembrolizumab offer moderate response rates (30-40%) and long survival (3- to 5-year survival: 30-50%). In Japan, treatment options for the first-line setting frequently include nivolumab or pembrolizumab monotherapy and BRAFi + MEKi combinations (for patients with BRAF-mutant melanoma). Ipilimumab is included in the second-line setting, and the nivolumab + ipilimumab combination has not been approved yet in Japan. Although these medications have demonstrated impressive efficacy, the clinical trials and real-world data have shown that the clinical benefit is not fully satisfactory. We have to carefully manage a new class of adverse events due to these medicines. Moreover, biomarkers are emerging with which we can identify a population that would experience more benefits without severe adverse events.