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

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

Y Nakamura  1 , K Namikawa  2 , K Yoshino  3 , S Yoshikawa  4 , H Uchi  5 , K Goto  6 , Y Nakamura  7 , S Fukushima  8 , Y Kiniwa  9 , T Takenouchi  10 , H Uhara  11 , T Kawai  12 , N Hatta  13 , T Funakoshi  14 , Y Teramoto  15 , A Otsuka  16 , H Doi  17 , D Ogata  18 , S Matsushita  19 , T Isei  20 , T Hayashi  21 , Y Shibayama  22 , N Yamazaki  2
Affiliations
Free article
Multicenter Study

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

Y Nakamura et al. Ann Oncol. 2020 Sep.
Free article

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.

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Conflict of interest statement

Disclosure YN has served as an advisor/consultant to MSD and Novartis and has received honoraria from Bristol-Myers Squibb, Maruho, MSD, Novartis, Ono Pharmaceutical, Taiho Pharmaceutical, and Taisho Toyama Pharma. KN has served as an advisor/consultant to Bristol-Myers Squibb, MSD, Novartis, and Ono Pharmaceutical, and has received honoraria from Bristol-Myers Squibb, Eisai, MSD, Novartis, Ono Pharmaceutical, Pharma International, Takara Bio, and Toray Industries. KY has served as an advisor/consultant to Brystol-Myers-Squibb, Novartis, and Ono Pharmaceutical, and has received honoraria from Bristol-Myers Squibb, Novartis, and Ono Pharmaceutical. SY has served as an advisor/consultant to Novartis and has received honoraria from Bristol-Myers Squibb, MSD, Novartis, and Ono Pharmaceutical. HU has received honoraria from Bristol-Myers Squibb, Novartis, and Ono Pharmaceutical. YN has received honoraria from Ono Pharmaceutical. SF receives institutional research funding from Brystol-Myers-Squibb, MSD, and Ono Pharmaceutical, and has received honoraria from MSD and Ono Pharmaceutical. TT has received honoraria from Bristol-Myers Squibb, MSD, Novartis, and Ono Pharmaceutical. HU receives institutional research funding from Abbvie, Daiichi Synkyo, Eisai, Kaken Pharmaceutical, Kyowa Hakko Kirin, Maruho, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical Co. Ltd., Nihonkayaku, Ono Pharmaceutical, Pola Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, and Tsumura & Co, has served as an advisor/consultant to Bristol-Myers Squibb, Chugai Pharma, Kyowa Hakko Kirin, MSD, Novartis, and Ono Pharmaceutical, and has received honoraria from Bristol-Myers Squibb, Chugai Pharma, Maruho, MSD, Novartis, Ono Pharmaceutical, Pola Pharma, Janssen China R&D, Kyowa Hakko Kirin, and Mitsubishi Tanabe Pharma. TF receives institutional research funding from MSD, Ono Pharmaceutical, and Zenyaku Kogyo, and has received honoraria from Bristol-Myers Squibb, Minophagen Pharmaceuticals, MSD, Novartis, and Ono Pharmaceutical. YT has received honoraria from Bristol-Myers Squibb, Maruho, and Ono Pharmaceutical. AO receives institutional research funding from Bristol-Myers Squibb and Ono Pharmaceutical and has received honoraria from Bristol-Myers Squibb and Ono Pharmaceutical. SM has received honoraria from Bristol-Myers Squibb, Kyowa Hakko Kirin, MSD, and Ono Pharmaceutical. TI has received honoraria from Bristol-Myers Squibb, MSD, Novartis, and Ono Pharmaceutical. NY receives institutional research funding from Bristol-Myers Squibb, MSD, Novartis, Ono Pharmaceutical, and Takara Bio, and has received honoraria from Bristol-Myers Squibb, MSD, Novartis, and Ono Pharmaceutical. None of these entities had any role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript. All remaining authors have declared no conflicts of interest.

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