Quantitative evaluation of the efficacy and safety of first-line systemic therapies for advanced hepatocellular carcinoma.

IF 2.4 3区医学 Q3 PHARMACOLOGY & PHARMACY

European Journal of Clinical Pharmacology Pub Date : 2025-03-01 Epub Date: 2024-12-28 DOI:10.1007/s00228-024-03797-0

Xinrui Wang, Jihan Huang, Yixiao Liu, Lijuan Wu, Ruifen Cai, Qingshan Zheng, Lujin Li

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引用次数: 0

Abstract

Objectives: This study aimed to quantitatively evaluate the efficacy and safety of first-line systemic therapies for treating advanced hepatocellular carcinoma (aHCC).

Methods: The study included clinical trials of first-line systemic therapies for aHCC since the approval of sorafenib in 2007. Hazard function models were used to describe changes in overall survival (OS) and progression-free survival (PFS) over time. Monte Carlo simulation was used to compare OS and PFS for different treatments, including sorafenib, antiangiogenic therapies (AATs) (except sorafenib), immune checkpoint inhibitor (ICI) monotherapy, AAT + targeted therapy, AAT + chemotherapy, AAT + ICIs, and ICIs + ICIs. Furthermore, the objective response rate (ORR) and incidence of grade ≥ 3 adverse events were analyzed.

Results: Fifty studies comprising 12,918 participants were included. AAT + ICIs demonstrated a significant benefit in median OS (mOS), median PFS (mPFS), and ORR (20.5 [95% CI 17.5-24] months, 7.5 [95% CI 6.5-8.8] months, and 24% [95% CI 17%-30%], respectively). ICIs + ICIs and ICI monotherapy ranked second and third, respectively with an mOS of 20 (95% CI 18.5-21.5) months and 14.5 (95% CI 13.5-16) months, respectively. The OS, PFS, and ORR of patients treated with AAT, AAT + targeted therapy, and AAT + chemotherapy were similar to those of patients treated with sorafenib. A higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage C had a shorter OS. OS was associated with publication year, and PFS was associated with the proportion of patients with BCLC stage C. The incidence of grade ≥ 3 adverse events in the ICIs and ICIs + ICIs treatment groups was low.

Conclusions: The study results provide valuable information from which to base rational clinical drug use and serves as a reliable external control for evaluating new treatments for aHCC.

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晚期肝细胞癌一线全身治疗的疗效和安全性定量评价。

目的：本研究旨在定量评价一线全身疗法治疗晚期肝细胞癌（aHCC）的疗效和安全性。方法：该研究包括自2007年索拉非尼获批以来aHCC一线全身治疗的临床试验。风险函数模型用于描述总生存期（OS）和无进展生存期（PFS）随时间的变化。采用蒙特卡罗模拟比较不同治疗的OS和PFS，包括索拉非尼、抗血管生成疗法（AATs）（索拉非尼除外）、免疫检查点抑制剂（ICI）单药治疗、AAT +靶向治疗、AAT +化疗、AAT + ICIs和ICIs + ICIs。分析客观缓解率（ORR）和≥3级不良事件发生率。结果：纳入了50项研究，包括12918名参与者。AAT + ICIs在中位OS （mOS）、中位PFS （mPFS）和ORR（分别为20.5 [95% CI 17.5-24]个月、7.5 [95% CI 6.5-8.8]个月和24% [95% CI 17%-30%]）方面显示出显著的益处。ICIs + ICIs和ICI单药治疗分别排名第二和第三，生存期分别为20个月（95% CI 18.5-21.5）和14.5个月（95% CI 13.5-16）。AAT、AAT +靶向治疗和AAT +化疗患者的OS、PFS和ORR与索拉非尼治疗患者相似。巴塞罗那临床肝癌（BCLC） C期患者的生存期较短的比例较高。OS与发表年份相关，PFS与BCLC c期患者比例相关。ICIs和ICIs + ICIs治疗组≥3级不良事件发生率较低。结论：研究结果为临床合理用药提供了有价值的信息，为评价aHCC的新治疗方法提供了可靠的外部对照。

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

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.