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)

被引：36

作者：

Nakamura, Y. ^{[1
]}

Namikawa, K. ^{[2
]}

Yoshikawa, S. ^{[3
]}

Kiniwa, Y. ^{[4
]}

Maekawa, T. ^{[5
]}

Yamasaki, O. ^{[6
]}

Isei, T. ^{[7
]}

Matsushita, S. ^{[8
]}

Nomura, M. ^{[9
]}

Nakai, Y. ^{[10
]}

Fukushima, S. ^{[11
]}

Saito, S. ^{[12
]}

Takenouchi, T. ^{[13
]}

Tanaka, R. ^{[14
]}

Kato, H. ^{[15
]}

Otsuka, A. ^{[16
]}

Matsuya, T. ^{[17
]}

Baba, N. ^{[18
]}

Nagase, K. ^{[19
]}

Inozume, T. ^{[20
]}

Fujimoto, N. ^{[21
]}

Kuwatsuka, Y. ^{[22
]}

Onishi, M. ^{[23
]}

Kaneko, T. ^{[24
]}

Onuma, T. ^{[25
]}

Umeda, Y. ^{[1
,14
]}

Ogata, D. ^{[2
]}

Takahashi, A. ^{[2
]}

Otsuka, M. ^{[3
]}

Teramoto, Y. ^{[1
]}

Yamazaki, N. ^{[2
]}

机构：

[1] Saitama Med Univ, Dept Skin Oncol Dermatol, Int Med Ctr, Saitama, Japan

[2] Natl Canc Ctr, Dept Dermatol Oncol, Tokyo, Japan

[3] Shizuoka Canc Ctr, Dept Dermatol, Shizuoka, Japan

[4] Shinshu Univ, Dept Dermatol, Matsumoto, Nagano, Japan

[5] Jichi Med Univ, Dept Dermatol, Shimotsuke, Tochigi, Japan

[6] Okayama Univ, Dept Dermatol, Grad Sch Med Dent & Pharmaceut Sci, Okayama, Japan

[7] Osaka Int Canc Inst, Dept Dermatol Oncol, Osaka, Japan

[8] Natl Hosp Org, Dept Dermatooncol Dermatol, Kagoshima Med Ctr, Kagoshima, Japan

[9] Kyoto Univ, Dept Clin Oncol, Kyoto, Japan

[10] Mie Univ, Dept Dermatol, Tsu, Mie, Japan

[11] Kumamoto Univ, Fac Life Sci, Dept Dermatol & Plast Surg, Kumamoto, Japan

[12] Gunma Univ, Dept Dermatol, Maebashi, Gumma, Japan

[13] Niigata Canc Ctr, Dept Dermatol, Niigata, Japan

[14] Kawasaki Med Sch, Dept Dermatol, Kurashiki, Okayama, Japan

[15] Nagoya City Univ, Dept Geriatr & Environm Dermatol, Grad Sch Med Sci, Nagoya, Aichi, Japan

[16] Kyoto Univ, Dept Dermatol, Kyoto, Japan

[17] Asahikawa Med Univ, Dept Dermatol, Asahikawa, Hokkaido, Japan

[18] Univ Fukui, Dept Dermatol, Fukui, Japan

[19] Saga Univ, Dept Internal Med, Div Dermatol, Saga, Japan

[20] Chiba Univ, Dept Dermatol, Chiba, Japan

[21] Shiga Univ Med Sci, Dept Dermatol, Otsu, Shiga, Japan

[22] Nagasaki Univ, Dept Dermatol, Nagasaki, Japan

[23] Iwate Med Univ, Dept Dermatol, Morioka, Iwate, Japan

[24] Juntendo Univ, Dept Dermatol, Urayasu Hosp, Urayasu, Japan

[25] Yamanashi Univ, Dept Dermatol, Kofu, Yamanashi, Japan

来源：

ESMO OPEN | 2021年 / 6卷 / 06期

关键词：

mucosal melanoma; anti-PD-1; antibody; anti-CTLA-4; nivolumab; pembrolizumab; ipilimumab; DISTINCT SUBTYPES; EFFICACY; SAFETY; NIVOLUMAB; IPILIMUMAB; TUMORS; KIT;

D O I：

10.1016/j.esmoop.2021.100325

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: 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. Patients and methods: 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. Results: 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). Conclusions: First-line PD1 + CTLA4 demonstrated comparable clinical efficacy to PD1 in Japanese MCM patients, but with a higher rate of immune-related adverse events.

引用

页数：9

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