Nakamura Y, Namikawa K, Yoshikawa S, Kiniwa Y, Maekawa T, Yamasaki O, Isei T, Matsushita S, Nomura M, Nakai Y, Fukushima S, Saito S, Takenouchi T, Tanaka R, Kato H, Otsuka A, Matsuya T, Baba N, Nagase K, Inozume T, Fujimoto N, Kuwatsuka Y, Onishi M, Kaneko T, Onuma T, Umeda Y, Ogata D, Takahashi A, Otsuka M, Teramoto Y, and Yamazaki N
Background: Anti-programmed cell death protein 1 (PD-1) antibody monotherapy (PD1) has led to favorable responses in advanced non-acral cutaneous melanoma among Caucasian populations; however, recent studies suggest that this therapy has limited efficacy in mucosal melanoma (MCM). Thus, advanced MCM patients are candidates for PD1 plus anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) combination therapy (PD1 + CTLA4). Data on the efficacy of immunotherapy in MCM, however, are limited. We aimed to compare the efficacies of PD1 and PD1 + CTLA4 in Japanese advanced MCM patients., Patients and Methods: We retrospectively assessed advanced MCM patients treated with PD1 or PD1 + CTLA4 at 24 Japanese institutions. Patient baseline characteristics, clinical responses (RECIST), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier analysis, and toxicity was assessed to estimate the efficacy and safety of PD1 and PD1 + CTLA4., Results: Altogether, 329 patients with advanced MCM were included in this study. PD1 and PD1 + CTLA4 were used in 263 and 66 patients, respectively. Baseline characteristics were similar between both treatment groups, except for age (median age 71 versus 65 years; P < 0.001). No significant differences were observed between the PD1 and PD1 + CTLA4 groups with respect to objective response rate (26% versus 29%; P = 0.26) or PFS and OS (median PFS 5.9 months versus 6.8 months; P = 0.55, median OS 20.4 months versus 20.1 months; P = 0.55). Cox multivariate survival analysis revealed that PD1 + CTLA4 did not prolong PFS and OS (PFS: hazard ratio 0.83, 95% confidence interval 0.58-1.19, P = 0.30; OS: HR 0.89, 95% confidence interval 0.57-1.38, P = 0.59). The rate of ≥grade 3 immune-related adverse events was higher in the PD1 + CTLA4 group than in the PD1 group (53% versus 17%; P < 0.001)., Conclusions: First-line PD1 + CTLA4 demonstrated comparable clinical efficacy to PD1 in Japanese MCM patients, but with a higher rate of immune-related adverse events., Competing Interests: Disclosure YN receives institutional research funding from Kaken, Ono Pharma, Pola Pharma, and Torii, and has served as a consultant and/or has received honoraria from Bristol Myers Squibb (BMS), Maruho, Merck Sharp & Dohme (MSD), Novartis, Ono Pharma, Taisho Toyama, and Taiho Pharma. KN has served as a consultant and/or has received honoraria from BMS, MSD, Novartis, and Ono Pharma. SY has received honoraria from Novartis and Ono Pharma. YK has received honoraria from Novartis and Ono Pharma. TM has received honoraria from BMS, MSD, Novartis, and Ono Pharma. OY has received research funding and/or honoraria from Ono Pharma. TI has served as a consultant and/or has received honoraria from Ono Pharma, Pfizer, BMS, and Novartis Pharma. SM has received honoraria from Ono Pharma. SF has received research funding from Ono Pharma. SS has received honoraria from Ono Pharma. TT has received honoraria from BMS, MSD, Novartis, and Ono Pharma. HK has received honoraria from Novartis and Ono Pharma. AO has served as a consultant and/or has received honoraria from BMS, MSD, Novartis, and Ono Pharma and received research funding from Eisai. TI has received honoraria from BMS, MSD, and Ono Pharma. YU has received honoraria from Ono and Novartis Pharma. YT has received honoraria from BMS, Maruho, MSD, Novartis, and Ono Pharma. NY receives institutional research funding from BMS, MSD, Novartis, Ono, Takara Bio, Amgen, and Merck Biopharma, and has served as consultant and/or has received honoraria from BMS, MSD, Novartis, and Ono Pharma. The other authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)