免疫检查点抑制剂治疗晚期肝细胞癌的III期随机对照试验中替代终点的评估

IF 2.4 3区医学 Q3 PHARMACOLOGY & PHARMACY

European Journal of Clinical Pharmacology Pub Date : 2025-05-01 Epub Date: 2025-03-13 DOI:10.1007/s00228-025-03820-y

Ke Jiang, Miaowen Liu, Xiao Zhao, Shutong Wang, Yunyan Ling, Liangliang Qiao, Jianfei Tu, Zhenwei Peng

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引用次数: 0

摘要

目的：总生存期（OS）被推荐为金标准终点，但有一些局限性。我们的目的是寻找免疫检查点抑制剂（ICIs）治疗晚期肝细胞癌（HCC）更有效的替代终点。方法：检索三个在线数据库，检索2015年1月至2023年7月发表的HCC随机对照试验（rct），评估ICIs并报告无进展生存期（PFS）、客观缓解率（ORR）、疾病控制率（DCR）和OS。在试验、组和患者水平上评估潜在替代终点和OS之间的相关性。预测模型在单臂或非随机对照试验中得到验证。个体数据收集自在中国三个三级医疗中心接受ICI单药治疗的现实世界晚期HCC （RW）队列。结果：纳入10项随机对照试验（6023名受试者），共11项比较。PFS与OS有中度显著相关（R2 = 0.50, p = 0.014）。ORR、DCR和OS呈弱相关。将分析限制在ICI单药治疗研究中，OS与PFS的相关性变得更强（R2 = 0.85, p = 0.02）。RW队列还证实，当患者接受ICI单药治疗时，PFS与OS密切相关。结论：推荐PFS作为ICI单药治疗晚期HCC患者的替代标志物。

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Evaluation of surrogate endpoints in phase III randomized control trials of advanced hepatocellular carcinoma treated with immune checkpoint inhibitors.

Purpose: Overall survival (OS) is recommended as a gold standard endpoint but has some limitations. We aimed to finding more effective surrogate endpoints for advanced hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs).

Methods: Three online databases were searched for randomized control trials (RCTs) on HCC, published between January 2015 and July 2023, that evaluated ICIs and reported progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and OS. The correlation between the potential surrogate endpoints and OS was evaluated at the trial, arm, and patient levels. The prediction models were validated in single-arm or non-RCTs. Individual data were collected from a real-world (RW) cohort with advanced HCC underwent ICI monotherapy at three tertiary medical centers in China.

Results: Ten RCTs (6023 participants) with 11 comparisons were included. PFS had a moderately significant association with OS (R² = 0.50, p = 0.014). ORR, DCR, and OS showed weak correlations. On limiting the analysis to ICI monotherapy studies, the correlations of OS with PFS became stronger (R² = 0.85, p = 0.02). The RW cohort also verified that PFS was closely related to OS when patient received with ICI monotherapy.

Conclusion: PFS are recommended as surrogate markers in patients with advanced HCC treated with ICI monotherapy.

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来源期刊

European Journal of Clinical Pharmacology 医学-药学

CiteScore

5.40

自引率

3.40%

发文量

170

审稿时长

3-8 weeks

期刊介绍： The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed. Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor. Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves -a compound that is interesting and new in some basic or fundamental way, or -methods that are original in some basic sense, or -a highly unexpected outcome, or -conclusions that are scientifically novel in some basic or fundamental sense.