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SYSTEMATIC REVIEW article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1468440
This article is part of the Research Topic Unveiling Biomarkers and Mechanisms in the Tumor-Immune Nexus View all 18 articles

Evaluation of the Effectiveness and Safety of Combining PD-1/PD-L1 Inhibitors with Anti-Angiogenic Agents in Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Provisionally accepted
Hengzhou Zhu Hengzhou Zhu *Wenyue Zhao Wenyue Zhao Haoyan Chen Haoyan Chen Xiaodan Zhu Xiaodan Zhu Jianliang You Jianliang You Chunhui Jin Chunhui Jin *
  • Wuxi Traditional Chinese Medicine Hospital, Wuxi, China

The final, formatted version of the article will be published soon.

    Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, particularly when diagnosed at an unresectable stage. Traditional treatments for advanced HCC have limited efficacy, prompting the exploration of combination therapies. This systematic review and meta-analysis evaluate the effectiveness and safety of combining PD-1/PD-L1 inhibitors with anti-angiogenic agents in patients with unresectable HCC. Methods: A comprehensive literature search was conducted in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science, including studies up to June 2024. Randomized controlled trials (RCTs) comparing combination therapy (PD-1/PD-L1 inhibitors with anti-angiogenic agents) to monotherapy or standard treatments in unresectable HCC patients were included.Data were synthesized using random-effects models, with pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and risk ratios (RRs) for objective response rate (ORR) and adverse events (AEs).Results: Five Phase III RCTs involving 1515 patients were included. Combination therapy significantly improved OS (HR: 0.71, 95% CI: 0.60-0.85) and PFS (HR: 0.64, 95% CI: 0.53-0.77) compared to monotherapy or standard treatments. The pooled OR for ORR was 1.27 (95% CI: 1.57-2.11), indicating a higher response rate with combination therapy. However, the risk of AEs was also higher in the combination therapy group (RR: 1.04, 95% CI: 1.02-1.06). Subgroup analyses revealed consistent benefits across different types of PD-1/PD-L1 inhibitors and anti-angiogenic agents, with no significant publication bias detected.The combination of PD-1/PD-L1 inhibitors with anti-angiogenic agents offers significant benefits in improving OS and PFS in patients with unresectable HCC, although it is associated with an increased risk of adverse events.

    Keywords: Hepatocellular Carcinoma, PD-1 inhibitors, anti-angiogenic therapy, combination therapy, overall survival

    Received: 22 Jul 2024; Accepted: 29 Aug 2024.

    Copyright: © 2024 Zhu, Zhao, Chen, Zhu, You and Jin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Hengzhou Zhu, Wuxi Traditional Chinese Medicine Hospital, Wuxi, China
    Chunhui Jin, Wuxi Traditional Chinese Medicine Hospital, Wuxi, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.