Efficacy and safety of lenvatinib combined with PD‑1/PD‑L1 inhibitors in the treatment of hepatocellular carcinoma: A meta‑analysis and systematic review

Zhang,Baoyan; Su,Linfeng; Lin,Yonghua

doi:10.3892/ol.2024.14445

Efficacy and safety of lenvatinib combined with PD‑1/PD‑L1 inhibitors in the treatment of hepatocellular carcinoma: A meta‑analysis and systematic review

Authors:
- Baoyan Zhang
- Linfeng Su
- Yonghua Lin
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Affiliations: Department of Pharmacy, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, P.R. China, Department of Hepatobiliary and Pancreatic Surgery, The Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
Published online on: May 14, 2024 https://doi.org/10.3892/ol.2024.14445
Article Number: 312
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

A meta‑analysis of the clinical survival indicators, adverse reactions and safety of lenvatinib combined with programmed death‑1 (PD‑1) inhibitors in treating liver cancer was conducted, providing objective and effective evidence for clinical use. The present study is anticipated to guide the clinical application of lenvatinib. In the current meta‑analysis, the PubMed, Embase and Cochrane Library databases were searched from inception to September 2023. Randomized controlled trials (RCTs), non‑RCTs and single‑arm trial studies related to the combined treatment of lenvatinib and PD‑1/PD‑ligand 1 (L1) inhibitors for hepatocellular carcinoma (HCC) were included, while published and unpublished literature on other study types, literature with incomplete or inadequate information, animal experiments, literature reviews and systematic studies were excluded. Data were processed using STATA 15.1. The pooled results showed that the objective response rate [ORR; odds ratio (OR), 3.36; 95% confidence interval (CI), 2.13‑5.30; P<0.001], disease control rate (DCR; OR, 1.62; 95% CI, 1.03‑2.57; P=0.038) and partial response (PR; OR, 3.81; 95% CI, 2.17‑6.70; P<0.001) of combined lenvatinib and PD‑1/PD‑L1 inhibitor therapy were significantly higher than those of lenvatinib monotherapy. Additionally, subgroup analysis results showed that the DCR of combination therapy using lenvatinib and nivolumab was significantly higher than that of lenvatinib monotherapy (OR, 2.20; 95% CI; 1.07‑4.51; P=0.032). The difference between combination therapy using lenvatinib and camrelizumab, and lenvatinib monotherapy was not significant. However, the complete response, stable disease, progression disease and incidence rate of adverse events between combination therapy and lenvatinib monotherapy were not significantly different. Compared with lenvatinib alone, lenvatinib combined with PD‑1/PD‑L1 inhibitors significantly improved ORR, mainly PR, and DCR in patients with HCC. At present, lenvatinib is mainly combined with nivolumab to increase the DCR of lenvatinib monotherapy for HCC. In addition, the incidence rate of adverse reactions between combination therapy and lenvatinib monotherapy was not significantly different for HCC.

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