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不同PD-1抑制剂联合乐伐替尼治疗不可切除原发性肝癌的疗效与安全性:一项多中心回顾性研究

Efficacy and safety of different PD-1 inhibitors in combination with lenvatinib in the treatment of unresectable primary liver cancer: a multicentre retrospective study.

作者信息

Li Qi-Mei, Sun Qing-Can, Jian Yan, He Jing-Zhe, Zhu Hong-Bo, Hong Chang, Zeng Lin, Li Rui-Ning, Wang Jia-Ren, Li Yan, Chen Li-Ya, Weng Xie, Liu Li, Dong Han-Zhi, Xiao Lu-Shan, Cui Hao

机构信息

Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

Department of Medical Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 330029, China.

出版信息

Discov Oncol. 2023 Jun 19;14(1):105. doi: 10.1007/s12672-023-00708-0.

Abstract

Immune checkpoint inhibitors (ICIs) are safe and efficacious treatments for advanced primary liver cancer (PLC). The efficacy of different ICIs in the treatment of liver cancer remains unclear. The purpose of this study was to explore whether there is a difference in the efficacy and safety of various programmed cell death protein 1 (PD-1) inhibitors in combination with lenvatinib in the treatment of unresectable PLC. Patients with PLC treated with lenvatinib in combination with PD-1 inhibitors (camrelizumab, tislelizumab, sintilimab, or pembrolizumab) between January 2018 and December 2021 were retrospectively enrolled. Tumor response, adverse events, and grades were evaluated. Kaplan-Meier analysis and log-rank test were used to compare the overall survival and progression-free survival of patients treated with different PD-1 inhibitors. Cox regression analysis was used for univariate and multivariate analyses to identify clinical variables related to treatment efficacy. This study included a total of 176 patients who received a combination of lenvatinib and PD-1 inhibitors. Of these, 103 patients received camrelizumab, 44 received tislelizumab, 20 received sintilimab, and 9 received pembrolizumab. There was no significant difference in the pairwise comparison of camrelizumab, tislelizumab, sintilimab, and pembrolizumab using Kaplan-Meier survival analysis. Adverse events occurred in 40 (22.7%) patients (grade ≥ 3, 2.3%). The incidence of grade 3 adverse events among the four PD-1 inhibitor groups was below 5%. Camrelizumab, tislelizumab, sintilimab, and pembrolizumab are viable options for patients with unresectable PLC. These PD-1 inhibitors in combination with lenvatinib showed good safety profiles. The results guide selecting treatment for patients with unresectable PLC.

摘要

免疫检查点抑制剂(ICIs)是治疗晚期原发性肝癌(PLC)的安全有效的方法。不同ICIs治疗肝癌的疗效尚不清楚。本研究的目的是探讨各种程序性细胞死亡蛋白1(PD-1)抑制剂联合乐伐替尼治疗不可切除PLC的疗效和安全性是否存在差异。回顾性纳入2018年1月至2021年12月期间接受乐伐替尼联合PD-1抑制剂(卡瑞利珠单抗、替雷利珠单抗、信迪利单抗或帕博利珠单抗)治疗的PLC患者。评估肿瘤反应、不良事件及分级。采用Kaplan-Meier分析和对数秩检验比较不同PD-1抑制剂治疗患者的总生存期和无进展生存期。采用Cox回归分析进行单因素和多因素分析,以确定与治疗疗效相关的临床变量。本研究共纳入176例接受乐伐替尼联合PD-1抑制剂治疗的患者。其中,103例接受卡瑞利珠单抗治疗,44例接受替雷利珠单抗治疗,20例接受信迪利单抗治疗,9例接受帕博利珠单抗治疗。使用Kaplan-Meier生存分析对卡瑞利珠单抗、替雷利珠单抗、信迪利单抗和帕博利珠单抗进行两两比较,差异无统计学意义。40例(22.7%)患者发生不良事件(≥3级,2.3%)。四个PD-1抑制剂组中3级不良事件的发生率均低于5%。卡瑞利珠单抗、替雷利珠单抗、信迪利单抗和帕博利珠单抗是不可切除PLC患者的可行选择。这些PD-1抑制剂联合乐伐替尼显示出良好的安全性。研究结果为不可切除PLC患者的治疗选择提供了指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3d5/10279630/4d8ec880402c/12672_2023_708_Fig1_HTML.jpg

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