Efficacy and safety of anti-PD-1 versus anti-PD-L1 in perioperative immunotherapy: A comprehensive reanalysis of randomized controlled trials.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2025-04-09 DOI:10.1016/j.medj.2025.100669

Chaoqi Zhang, Peng Wu, Dongyu Li, Junhan Zhou, Chuqi Lin, Xuanyu Gu, Dexin Shang, Ruijie Ma, Jingjing Liu, Guochao Zhang, Pan Wang, Yun Che, Qingpeng Zeng, Jilin Peng, Bohui Zhao, Nan Sun, Jie He

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引用次数: 0

Abstract

Background: Perioperative anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) immune checkpoint inhibitors improve outcomes, but optimal selection between agents remains debated. We compared the efficacy and safety of anti-PD-1 versus anti-PD-L1 in neoadjuvant/adjuvant settings.

Methods: PubMed, Embase, Cochrane CENTRAL, and major oncology conferences (up to May 20, 2024) were systematically searched for randomized trials comparing anti-PD-1/PD-L1 with standard perioperative therapy. Data extraction followed PRISMA guidelines, including trial characteristics, efficacy outcomes (pathological response and survival outcome), and safety profiles. Indirect comparisons between agents were conducted through network meta-analysis employing the mirror principle, utilizing both frequentist and Bayesian methodologies.

Findings: Thirty-one trials (14,974 patients) were analyzed. Anti-PD-1 demonstrated superior pathological complete response (relative risk [RR]: 1.65, 95% confidence interval [CI]: 1.18-2.29, p = 0.003), major pathological response (RR: 1.43, 95% CI: 1.04-1.96, p = 0.026), and disease-free survival (hazard ratio [HR] = 0.82, 95% CI: 0.71-0.96, p = 0.0106) versus anti-PD-L1. Safety profiles were comparable overall, though anti-PD-1 correlated with higher grade 3-5 immune-related adverse events (irAEs). Frequentist and Bayesian analyses yielded consistent results.

Conclusions: Perioperative anti-PD-1 therapy shows enhanced efficacy but increased severe irAEs compared to anti-PD-L1, supporting agent-specific considerations in clinical practice. Further tumor-specific evaluations and mature data are warranted.

Funding: This work is supported in part by the CAMS Innovation Fund for Medical Sciences (2024-I2M-ZD-004) and so on.

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围手术期免疫治疗中抗pd -1与抗pd - l1的疗效和安全性：随机对照试验的综合再分析

背景：围手术期抗程序性细胞死亡1 (PD-1)/PD配体1 （PD- l1）免疫检查点抑制剂可改善预后，但药物之间的最佳选择仍存在争议。我们比较了抗pd -1和抗pd - l1在新辅助/辅助治疗中的疗效和安全性。方法：系统检索PubMed， Embase， Cochrane CENTRAL和主要肿瘤学会议（截至2024年5月20日），以比较抗pd -1/PD-L1与标准围手术期治疗的随机试验。数据提取遵循PRISMA指南，包括试验特征、疗效结局（病理反应和生存结局）和安全性概况。代理人之间的间接比较是通过采用镜像原则的网络元分析进行的，同时利用频率论和贝叶斯方法。结果：31项试验（14974例患者）被分析。抗pd -1表现出优于抗pd - l1的病理完全缓解（相对危险度[RR]: 1.65, 95%可信区间[CI]: 1.18-2.29, p = 0.003）、主要病理缓解（RR: 1.43, 95% CI: 1.04-1.96, p = 0.026）和无病生存（风险比[HR] = 0.82, 95% CI: 0.71-0.96, p = 0.0106）。尽管抗pd -1与较高级别的3-5级免疫相关不良事件（irAEs）相关，但总体上的安全性可比较。频率分析和贝叶斯分析得出了一致的结果。结论：与抗pd - l1相比，围手术期抗pd -1治疗的疗效增强，但严重的irAEs发生率增加，在临床实践中支持药物特异性考虑。进一步的肿瘤特异性评估和成熟的数据是必要的。资助：本工作得到CAMS医学科学创新基金（2024-I2M-ZD-004）等的部分支持。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.