Anti-PD-1 antibody monotherapy versus anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy in unresectable or metastatic mucosal melanoma: a retrospective, multicenter study of 329 Japanese cases (JMAC study)

• Published in: ESMO open Vol. 6; no. 6; p. 100325
• Main Authors: 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., Yamazaki, N.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-12-2021; Elsevier
• Subjects: Aged; anti-CTLA-4 antibody; anti-PD-1 antibody; CTLA-4 Antigen; Humans; Immunotherapy - methods; ipilimumab; Japan; Melanoma - drug therapy; mucosal melanoma; nivolumab; Original Research; pembrolizumab; Retrospective Studies; Skin Neoplasms; Japan; anti-PD-1 antibody; pembrolizumab; mucosal melanoma; nivolumab; anti-CTLA-4 antibody; ipilimumab
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2021.100325

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.
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.
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).
First-line PD1 + CTLA4 demonstrated comparable clinical efficacy to PD1 in Japanese MCM patients, but with a higher rate of immune-related adverse events.
•Anti-PD-1 plus anti-CTLA-4 antibody therapy (PD1 + CTLA4) is an option for patients with advanced mucosal melanoma (MCM).•Data on the efficacy of PD1 + CTLA4 compared with PD-1 monotherapy (PD1) for MCM, however, are limited.•We retrospectively analyzed data from 329 Japanese patients with advanced MCM treated with PD1 or PD1 + CTLA4.•No significant differences in objective response rate, progression-free survival, or overall survival were observed.•Immune-related adverse events resulting in treatment cessation were higher in the PD1 + CTLA4 group.