Zhang Baoyan, Su Linfeng, Lin Yonghua
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.
Oncol Lett. 2024 May 14;28(1):312. doi: 10.3892/ol.2024.14445. eCollection 2024 Jul.
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lenvatinib and PD-1/PD-ligand 1 (L1) inhibitors for hepatocellular carcinoma (HCC) were included, while published and unpublished literature on other study types, literature with incomplete or inadequate information, animal experiments, literature reviews and systematic studies were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.
对乐伐替尼联合程序性死亡-1（PD-1）抑制剂治疗肝癌的临床生存指标、不良反应及安全性进行了荟萃分析，为临床应用提供客观有效的依据。本研究有望指导乐伐替尼的临床应用。在本次荟萃分析中，检索了PubMed、Embase和Cochrane图书馆数据库，检索时间从建库至2023年9月。纳入了与乐伐替尼和PD-1/PD-配体1（L1）抑制剂联合治疗肝细胞癌（HCC）相关的随机对照试验（RCT）、非RCT和单臂试验研究，排除了其他研究类型的已发表和未发表文献、信息不完整或不足的文献、动物实验、文献综述和系统研究。使用STATA 15.1对数据进行处理。汇总结果显示，乐伐替尼与PD-1/PD-L1抑制剂联合治疗的客观缓解率[ORR；优势比（OR），3.36；95%置信区间（CI），2.13 - 5.30；P<0.001]、疾病控制率（DCR；OR，1.62；95%CI，1.03 - 2.57；P = 0.038）和部分缓解（PR；OR，3.81；95%CI，2.17 - 6.70；P<0.001）显著高于乐伐替尼单药治疗。此外，亚组分析结果显示，乐伐替尼与纳武利尤单抗联合治疗的DCR显著高于乐伐替尼单药治疗（OR，2.20；95%CI；1.07 - 4.51；P = 0.032）。乐伐替尼与卡瑞利珠单抗联合治疗与乐伐替尼单药治疗之间的差异不显著。然而，联合治疗与乐伐替尼单药治疗之间的完全缓解、病情稳定、疾病进展及不良事件发生率无显著差异。与单用乐伐替尼相比，乐伐替尼联合PD-1/PD-L1抑制剂显著提高了HCC患者的ORR，主要是PR和DCR。目前，乐伐替尼主要与纳武利尤单抗联合使用，以提高乐伐替尼单药治疗HCC的DCR。此外，联合治疗与乐伐替尼单药治疗在HCC患者中的不良反应发生率无显著差异。
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