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Meta-Analysis
. 2024 Sep 17:15:1468440.
doi: 10.3389/fimmu.2024.1468440. eCollection 2024.

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

Hengzhou Zhu  1 , Wenyue Zhao  1 , Haoyan Chen  2 , Xiaodan Zhu  1 , Jianliang You  1 , Chunhui Jin  1
Affiliations
Meta-Analysis

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

Hengzhou Zhu et al. Front Immunol. .

Abstract

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.

Conclusions: 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: PD-1 inhibitors; anti-angiogenic therapy; combination therapy; hepatocellular carcinoma; overall survival.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Literature search process.
Figure 2
Figure 2
Risks of bias. (A) Risk of bias summary (B) Risk of bias assessment.
Figure 3
Figure 3
Meta-analysis of DCR. (A) Forest plot for DCR (B) Funnel plot for DCR (C) Forest plot for DCR1.1 (D) Funnel plot for DCR 1.1.
Figure 4
Figure 4
Meta-analysis of ORR. (A) Forest plot for ORR (OS) (B) Funnel plot for ORR (C) Forest plot for ORR 1.1 (D) Funnel plot for ORR 1.1.
Figure 5
Figure 5
Meta-analysis of OS. (A) Forest plot for OS (B) Funnel plot for OS.
Figure 6
Figure 6
Meta-analysis of PFS. (A) Forest plot for PFS (B) Funnel plot for PFS.
Figure 7
Figure 7
Meta-analysis of adverse event. (A) Forest plot for adverse event (B) Funnel plot for adverse event.
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