Analyzing the relationship between the efficacy of first-line immune checkpoint inhibitors and cumulative sun damage in Japanese patients with advanced BRAF wild-type nonacral cutaneous melanoma: A retrospective real-world, multicenter study.

BACKGROUND

Efficacy of anti-PD-1 antibody monotherapy (PD1) or anti-PD-1 plus anti-CTLA-4 combination therapy (PD1 +CTLA4) for melanoma is affected by its clinical subtype. The amount of tumor mutation burden (TMB) caused by cumulative sun damage (CSD) is occasionally used to explain this; however, their relationship in Japanese nonacral cutaneous melanoma (NACM) is still unclear.

OBJECTIVE

To analyze the ICI efficacy and its relationship with CSD of the primary lesion in Japanese patients with NACM.

METHODS

Japanese patients with advanced BRAF wild-type NACM who received first-line ICIs were recruited. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), and the degree of solar elastosis (SE) were evaluated.

RESULTS

A total of 146 patients (PD1 group 113 and PD1 +CTLA4 group 33) were included. No significant differences in ORR were observed between the PD1 and PD1 +CTLA4 groups (35 % vs. 36 %; P = 0.67) or PFS and OS (median PFS 6.1 months vs. 8.5 months; P = 0.46, median OS 28.1 months vs. not reached; P = 0.59). Multivariate survival analysis revealed that PD1 +CTLA4 did not prolong the PFS and OS. The SE score had no effect on either PFS or OS.

CONCLUSIONS

ICI efficacy was not as high as those reported in Western countries, and PD1 +CTLA4 did not present better clinical efficacy compared to PD1. Indicators of CSD did not serve as a predictor for clinical advantage. These findings may partially support the theory that ICI efficacy is affected by CSD; however, other unrecognized factors may also exist.

Informations de copyright

Copyright © 2023 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest Takashi Inozume has received honoraria from Bristol-Myers Squibb (BMS), Ono Pharma, and MSD. Kenjiro Namikawa has served as a consultant or/and has received honoraria from BMS, MSD, Novartis, and Ono Pharma. Hiroshi Kato has received honoraria from Novartis and Ono Pharma. Shusuke Yoshikawa has received honoraria from Novartis and Ono Pharma. Yukiko Kiniwa has received honoraria from Novartis and Ono Pharma. Tatsuya Takenouchi has received honoraria BMS, MSD, Novartis, and Ono Pharma. Shigeto Matsushita has received honoraria from BMS, MSD, Novartis, and Ono Pharma. Yasuhiro Fujisawa received honoraria from BMS, MSD, Novartis, Ono Pharma, and Eizai. Takeo Maekawa has received honoraria from BMS, MSD, Novartis, and Ono Pharma. Taiki Isei has served as a consultant or/and has received honoraria from Ono, Pfizer, BMS, and Novartis Pharma. Masahito Yasuda received honoraria from Novartis. Naoya Yamazaki receives institutional research funding from BMS, MSD, Novartis, Ono, and Takara Bio, and has served as consultant or/and has received honoraria from BMS, MSD, Novartis, and Ono Pharma. Hisashi Uhara received honoraria from BMS, MSD, Novartis, Ono Pharma, Taiho, Sun Pharma, Mitsubishi Tanabe Pharma, Janssen Pharma, Kyowa Hakko Kirin, and Merck Biopharma Co. Yasuhiro Nakamura has served as a consultant or/and has received honoraria from MSD, Novartis, BMS, Maruho, Ono Pharma, Taisho Toyama, and Taiho Pharma. The other authors have no conflicts of interest to disclose.