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).
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).
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DOI：
10.1016/j.esmoop.2021.100325
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发表时间：
2021-12
期刊：
影响因子：
7.3
通讯作者：
Yamazaki N
中科院分区：
文献类型：
--
作者：
Nakamura Y;Namikawa K;Yoshikawa S;Kiniwa Y;Maekawa T;Yamasaki O;Isei T;Matsushita S;Nomura M;Nakai Y;Fukushima S;Saito S;Takenouchi T;Tanaka R;Kato H;Otsuka A;Matsuya T;Baba N;Nagase K;Inozume T;Fujimoto N;Kuwatsuka Y;Onishi M;Kaneko T;Onuma T;Umeda Y;Ogata D;Takahashi A;Otsuka M;Teramoto Y;Yamazaki N
抗程序性细胞死亡蛋白1（PD-1）抗体单药治疗（PD 1）已在高加索人群中的晚期非肢端皮肤黑色素瘤中产生了有利的缓解;然而，最近的研究表明，该疗法在粘膜黑色素瘤（MCM）中的疗效有限。因此，晚期MCM患者是PD 1加抗细胞毒性T淋巴细胞相关抗原-4（CTLA-4）联合治疗（PD 1 + CTLA 4）的候选者。然而，关于免疫疗法在MCM中的疗效的数据有限。我们的目的是比较PD 1和PD 1 + CTLA 4在日本晚期MCM患者中的疗效。我们回顾性评估了24家日本机构接受PD 1或PD 1 + CTLA 4治疗的晚期MCM患者。使用Kaplan-Meier分析估计患者基线特征、临床应答（RECIST）、无进展生存期（PFS）和总生存期（OS），并评估毒性以估计PD 1和PD 1 + CTLA 4的疗效和安全性。共有329例晚期MCM患者纳入本研究。PD 1和PD 1 + CTLA 4分别用于263例和66例患者。两个治疗组的基线特征相似，除了年龄（中位年龄71岁vs 65岁; P < 0.001）。在客观缓解率（26% vs 29%; P = 0.26）或PFS和OS（中位PFS 5.9个月vs 6.8个月; P = 0.55，中位OS 20.4个月vs 20.1个月; P = 0.55）方面，未观察到PD 1组和PD 1 + CTLA 4组之间存在显著差异。考克斯多变量生存分析显示，PD 1 + CTLA 4未延长PFS和OS（PFS：风险比0.83，95%置信区间0.58-1.19，P = 0.30; OS：HR 0.89，95%置信区间0.57-1.38，P = 0.59）。PD 1 + CTLA 4组中≥ 3级免疫相关不良事件的发生率高于PD 1组（53% vs 17%; P < 0.001）。在日本MCM患者中，一线PD 1 + CTLA 4的临床疗效与PD 1相当，但免疫相关不良事件发生率更高。抗PD-1加抗CTLA-4抗体治疗（PD 1 + CTLA 4）是晚期粘膜黑色素瘤（MCM）患者的一种选择。然而，与PD-1单药治疗（PD 1）相比，PD 1 + CTLA 4治疗MCM的疗效数据有限。我们回顾性分析了329例接受PD 1或PD 1 + CTLA 4治疗的日本晚期MCM患者的数据。客观缓解率、无进展生存期或总生存期无显著差异。导致治疗停止的免疫相关不良事件在PD 1 + CTLA 4组中更高。
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. 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. 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). First-line PD1 + CTLA4 demonstrated comparable clinical efficacy to PD1 in Japanese MCM patients, but with a higher rate of immune-related adverse events. Anti-PD-1 plus anti-CTLA-4 antibody therapy (PD1 + CTLA4) is an option for patients with advanced mucosal melanoma (MCM). Data on the efficacy of PD1 + CTLA4 compared with PD-1 monotherapy (PD1) for MCM, however, are limited. We retrospectively analyzed data from 329 Japanese patients with advanced MCM treated with PD1 or PD1 + CTLA4. No significant differences in objective response rate, progression-free survival, or overall survival were observed. Immune-related adverse events resulting in treatment cessation were higher in the PD1 + CTLA4 group.
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