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.
KeywordsMelanoma Japan Immune checkpoint inhibitors BRAF inhibitors MEK inhibitors Biomarker
This work was partially supported by JSPS KAKENHI Grant Number JP16K10150.
Compliance with ethical standards
Conflict of interest
Funds and Grant for research: ONO PHARMACEUTICAL CO., LTD, Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd. Novartis, MSD, TAIHO Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Kyowa Hakko Kirin Company, Limited, Mitsubishi Tanabe Pharma Corporation, Esai, AbbVie, Maruho, DAIICHI SANKYO COMPANY, LIMITED, Tsumura, Porafarma, Mochida, Nihonkayaku, Acterion, Torii, KAKEN PHARMACEUTICAL CO., LTD. Consultancy fee: ONO PHARMACEUTICAL CO., LTD, Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd. Novartis, MSD, Kyowa Hakko Kirin Company, Limited: Fee for speaking. ONO PHARMACEUTICAL CO., LTD, Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd. Novartis, MSD, TAIHO Pharmaceutical Co., Ltd. Porafarma, Mitsubishi Tanabe Pharma Corporation, Maruho.
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