Efficacy of salvage therapies for advanced acral melanoma after anti-PD-1 monotherapy failure: a multicenter retrospective study of 108 Japanese patients

Tatsuhiko Mori; Kenjiro Namikawa; Naoya Yamazaki; Yukiko Kiniwa; Osamu Yamasaki; Shusuke Yoshikawa; Takashi Inozume; Hiroshi Kato; Yasuo Nakai; Satoshi Fukushima; Tatsuya Takenouchi; Takeo Maekawa; Shigeto Matsushita; Atsushi Otsuka; Motoo Nomura; Natsuki Baba; Taiki Isei; Shintaro Saito; Noriki Fujimoto; Ryo Tanaka; Takahide Kaneko; Yutaka Kuwatsuka; Taisuke Matsuya; Kotaro Nagase; Masazumi Onishi; Takehiro Onuma; Yasuhiro Nakamura

doi:10.3389/fmed.2023.1229937

Efficacy of salvage therapies for advanced acral melanoma after anti-PD-1 monotherapy failure: a multicenter retrospective study of 108 Japanese patients

Front Med (Lausanne). 2023 Aug 10:10:1229937. doi: 10.3389/fmed.2023.1229937. eCollection 2023.

Authors

Tatsuhiko Mori¹, Kenjiro Namikawa², Naoya Yamazaki², Yukiko Kiniwa³, Osamu Yamasaki⁴, Shusuke Yoshikawa⁵, Takashi Inozume⁶, Hiroshi Kato⁷, Yasuo Nakai⁸, Satoshi Fukushima⁹, Tatsuya Takenouchi¹⁰, Takeo Maekawa¹¹, Shigeto Matsushita¹², Atsushi Otsuka^{13

14}, Motoo Nomura¹⁵, Natsuki Baba¹⁶, Taiki Isei¹⁷, Shintaro Saito¹⁸, Noriki Fujimoto¹⁹, Ryo Tanaka²⁰, Takahide Kaneko²¹, Yutaka Kuwatsuka²², Taisuke Matsuya²³, Kotaro Nagase²⁴, Masazumi Onishi²⁵, Takehiro Onuma²⁶, Yasuhiro Nakamura¹

Affiliations

¹ Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center, Saitama, Japan.
² Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
³ Department of Dermatology, Shinshu University, Matsumoto, Japan.
⁴ Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
⁵ Division of Dermatology, Shizuoka Cancer Center, Shizuoka, Japan.
⁶ Department of Dermatology, Chiba University, Chiba, Japan.
⁷ Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
⁸ Department of Dermatology, Mie University, Mie, Japan.
⁹ Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
¹⁰ Department of Dermatology, Niigata Cancer Center Hospital, Niigata, Japan.
¹¹ Department of Dermatology, Jichi Medical University, Tochigi, Japan.
¹² Department of Dermato-Oncology/Dermatology, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan.
¹³ Department of Dermatology, Kyoto University, Kyoto, Japan.
¹⁴ Department of Dermatology, Kindai University Hospital, Osaka, Japan.
¹⁵ Department of Clinical Oncology, Kyoto University, Kyoto, Japan.
¹⁶ Department of Dermatology, University of Fukui, Fukui, Japan.
¹⁷ Department of Dermatologic Oncology, Osaka International Cancer Institute, Osaka, Japan.
¹⁸ Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
¹⁹ Department of Dermatology, Shiga University of Medical Science, Otsu, Japan.
²⁰ Department of Dermatology, Kawasaki Medical School, Kurashiki, Japan.
²¹ Department of Dermatology, Juntendo University Urayasu Hospital, Chiba, Japan.
²² Department of Dermatology, Nagasaki University, Nagasaki, Japan.
²³ Department of Dermatology, Asahikawa Medical University, Asahikawa, Japan.
²⁴ Division of Dermatology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
²⁵ Department of Dermatology, Iwate Medical University, Iwate, Japan.
²⁶ Department of Dermatology, University of Yamanashi, Yamanashi, Japan.

Abstract

Background: Anti-programmed cell death protein 1 (PD-1) monotherapy is one of the standard systemic therapies for advanced melanoma; however, the efficacy of salvage systemic therapies after PD-1 monotherapy failure (PD-1 MF), particularly in acral melanoma (AM), the main clinical melanoma type in Japanese patients, is unclear. This study aimed to investigate the efficacy of salvage systemic therapies in Japanese patients with AM after PD-1 MF.

Patients and methods: The study included 108 patients with advanced AM (palm and sole, 72; nail apparatus, 36) who underwent salvage systemic therapy at 24 Japanese institutions. We mainly assessed the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results: Thirty-six (33%) patients received ipilimumab, 23 (21%) received nivolumab and ipilimumab (nivo/ipi), 10 (9%) received cytotoxic chemotherapy, 4 (4%) received BRAF and MEK inhibitors (BRAFi/MEKi), and the remaining 35 (32%) continued with PD-1 monotherapy after disease progression. The ORRs in the ipilimumab, nivo/ipi, cytotoxic chemotherapy, and BRAFi/MEKi groups were 8, 17, 0, and 100%, respectively. The nivo/ipi group showed the longest OS (median, 18.9 months); however, differences in ORR, PFS, and OS between the groups were insignificant. The OS in the nivo/ipi group was higher in the palm and sole groups than in the nail apparatus group (median: not reached vs. 8.7 months, p < 0.001). Cox multivariate analysis demonstrated that nail apparatus melanoma independently predicted unfavorable PFS and OS (p = 0.006 and 0.001). The total OS (from PD-1 monotherapy initiation to death/last follow-up) was insignificant between the groups.

Conclusion: Nivo/ipi was not more effective than cytotoxic chemotherapy and ipilimumab after PD-1 MF in patients with advanced AM. The prognosis after PD-1 MF would be poorer for nail apparatus melanoma than for palm and sole melanoma.

Keywords: immunotherapy; melanoma; nails; programmed cell death 1 receptor; salvage therapy.

Copyright © 2023 Mori, Namikawa, Yamazaki, Kiniwa, Yamasaki, Yoshikawa, Inozume, Kato, Nakai, Fukushima, Takenouchi, Maekawa, Matsushita, Otsuka, Nomura, Baba, Isei, Saito, Fujimoto, Tanaka, Kaneko, Kuwatsuka, Matsuya, Nagase, Onishi, Onuma and Nakamura.