Anti-PD1 checkpoint inhibitor therapy in acral melanoma: a multicenter study of 193 Japanese patients

Y Nakamura; K Namikawa; K Yoshino; S Yoshikawa; H Uchi; K Goto; Y Nakamura; S Fukushima; Y Kiniwa; T Takenouchi; H Uhara; T Kawai; N Hatta; T Funakoshi; Y Teramoto; A Otsuka; H Doi; D Ogata; S Matsushita; T Isei; T Hayashi; Y Shibayama; N Yamazaki

doi:10.1016/j.annonc.2020.05.031

Anti-PD1 checkpoint inhibitor therapy in acral melanoma: a multicenter study of 193 Japanese patients

Ann Oncol. 2020 Sep;31(9):1198-1206. doi: 10.1016/j.annonc.2020.05.031. Epub 2020 Jun 6.

Authors

Y Nakamura¹, K Namikawa², K Yoshino³, S Yoshikawa⁴, H Uchi⁵, K Goto⁶, Y Nakamura⁷, S Fukushima⁸, Y Kiniwa⁹, T Takenouchi¹⁰, H Uhara¹¹, T Kawai¹², N Hatta¹³, T Funakoshi¹⁴, Y Teramoto¹⁵, A Otsuka¹⁶, H Doi¹⁷, D Ogata¹⁸, S Matsushita¹⁹, T Isei²⁰, T Hayashi²¹, Y Shibayama²², N Yamazaki²

Affiliations

¹ Department of Skin Oncology/Dermatology, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan. Electronic address: ynakamur@saitama-med.ac.jp.
² Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
³ Department of Dermatologic Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
⁴ Department of Dermatology, Shizuoka Cancer Center, Shizuoka, Japan.
⁵ Department of Dermatology, Kyushu University, Fukuoka, Japan.
⁶ Department of Dermatology, Nagoya University, Nagoya, Japan.
⁷ Department of Dermatology, University of Tsukuba, Tsukuba, Japan.
⁸ Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
⁹ Department of Dermatology, Shinshu University, Matsumoto, Japan.
¹⁰ Department of Dermatology, Niigata Cancer Center, Niigata, Japan.
¹¹ Department of Dermatology, Sapporo Medical University, Sapporo, Japan.
¹² Department of Dermatology, University of Tokyo, Tokyo, Japan.
¹³ Department of Dermatology, Toyama Prefectural Central Hospital, Toyama, Japan.
¹⁴ Department of Dermatology, Keio University, Tokyo, Japan.
¹⁵ Department of Skin Oncology/Dermatology, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan.
¹⁶ Department of Dermatology, Kyoto University, Kyoto, Japan.
¹⁷ Department of Dermatology, Asahikawa Medical University, Asahikawa, Japan.
¹⁸ Department of Dermatology, Saitama Medical University, Saitama, Japan.
¹⁹ Department of Dermato-Oncology/Dermatology, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan.
²⁰ Department of Dermatological Oncology, Osaka International Cancer Institute, Osaka, Japan.
²¹ Plastic and Reconstructive Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
²² Department of Dermatology, Fukuoka University, Fukuoka, Japan.

PMID: 32522691
DOI: 10.1016/j.annonc.2020.05.031

Abstract

Background: Acral melanoma (AM) is an epidemiologically and molecularly distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. We aimed to analyze the efficacy of anti-programmed cell death 1 (anti-PD-1) antibodies in advanced AM.

Patients and methods: We retrospectively evaluated unresectable stage III or stage IV AM patients treated with an anti-PD-1 antibody in any line at 21 Japanese institutions between 2014 and 2018. The clinicobiologic characteristics, objective response rate (ORR, RECIST), survival estimated using Kaplan-Meier analysis, and toxicity (Common Terminology Criteria for Adverse Events 4.0.) were analyzed to estimate the efficacy of the anti-PD-1 antibodies.

Results: In total, 193 patients (nail apparatus, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 patients (74.1%). Baseline lactate dehydrogenase (LDH) was within the normal concentration in 102 patients (52.8%). The ORR of all patients was 16.6% (complete response, 3.1%; partial response, 13.5%), and the median overall survival (OS) was 18.1 months. Normal LDH concentrations showed a significantly stronger association with better OS than abnormal concentrations (median OS 24.9 versus 10.7 months; P < 0.001). Although baseline characteristics were similar between the nail apparatus and the palm and sole groups, ORR was significantly lower in the nail apparatus group [6/70 patients (8.6%) versus 26/123 patients (21.1%); P = 0.026]. Moreover, the median OS in this group was significantly poorer (12.8 versus 22.3 months; P = 0.03).

Conclusions: Anti-PD-1 antibodies have limited efficacy in AM patients. Notably, patients with nail apparatus melanoma had poorer response and survival, making nail apparatus melanoma a strong candidate for further research on the efficacy of novel combination therapies with immune checkpoint inhibitors.

Keywords: acral melanoma; anti-PD-1 antibody; efficacy; malignant melanoma; nivolumab; pembrolizumab.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Japan
Melanoma* / drug therapy
Programmed Cell Death 1 Receptor
Retrospective Studies
Skin Neoplasms* / drug therapy

Substances

Programmed Cell Death 1 Receptor