Zhao Lingling, Xu Cheng, Deng Jiewen, Ni Yang
Department of General Surgery, Sichuan Science City Hospital, Mianyang, China.
Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China.
Front Oncol. 2025 Feb 12;15:1513394. doi: 10.3389/fonc.2025.1513394. eCollection 2025.
BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) is increasingly recognized as a primary treatment option for patients with unresectable hepatocellular carcinoma (uHCC), providing a focused treatment for localized tumors. The combination of lenvatinib, a multikinase inhibitor, with PD-1 inhibitors has demonstrated significant survival benefits in HCC. This meta-analysis aims to assess whether the integration of HAIC with lenvatinib and PD-1 inhibitors (referred to as the HAIC-L-P group) leads to better treatment effectiveness and security compared to lenvatinib and PD-1 inhibitors alone (L-P group) in uHCC. METHODS: An exhaustive search of the literature was conducted, including PubMed, the Cochrane Library, Embase, ClinicalTrials.gov, and Web of Science, from the start of each database until September 2024, to ensure a thorough and up-to-date compilation of relevant studies. Extract data on outcome measures such as overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Subsequently, meta-analyses were performed using RevMan 5.4 to quantitatively evaluate the aggregated effect of the HAIC-L-P regimen versus the L-P regimen alone. RESULTS: In our systematic meta-analysis of eight retrospective cohort studies, the HAIC-L-P regimen demonstrated markedly enhanced OS, with an HR of 0.54 (95% CI: 0.45-0.64; p < 0.00001), and enhanced 1-year and 2-year OS rates. Superior PFS was also observed in the HAIC-L-P group, with an HR of 0.64 (95% CI: 0.55-0.75; p < 0.0001), and higher 1-year and 2-year PFS rates. Response rates were markedly higher in the HAIC-L-P group, with an ORR risk ratio of 2.15 (95% CI: 1.84-2.50; p < 0.00001) and a DCR risk ratio of 1.28 (95% CI: 1.20-1.43; p < 0.0001). The AEs classified as grade 3 or above were elevated in the HAIC-L-P group, with notable risk ratios for vomiting, elevated AST, elevated ALT, thrombocytopenia, neutropenia, and hyperbilirubinemia. No life-threatening AEs were reported. CONCLUSION: The HAIC-L-P regimen correlated with enhanced tumor responses and prolonged survival, alongside manageable adverse effects, indicating its potential as a viable therapeutic strategy for individuals afflicted with uHCC. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024594109.
背景：肝动脉灌注化疗（HAIC）越来越被认为是不可切除肝细胞癌（uHCC）患者的主要治疗选择，为局部肿瘤提供了针对性治疗。多激酶抑制剂乐伐替尼与PD-1抑制剂联合使用已在肝癌中显示出显著的生存获益。本荟萃分析旨在评估与单独使用乐伐替尼和PD-1抑制剂（L-P组）相比，HAIC联合乐伐替尼和PD-1抑制剂（称为HAIC-L-P组）在uHCC中是否能带来更好的治疗效果和安全性。 方法：对文献进行了全面检索，包括PubMed、Cochrane图书馆、Embase、ClinicalTrials.gov和Web of Science，从每个数据库建立之初至2024年9月，以确保全面且最新地汇编相关研究。提取总生存（OS）、无进展生存（PFS）、客观缓解率（ORR）、疾病控制率（DCR）和不良事件（AE）等结局指标的数据。随后，使用RevMan 5.4进行荟萃分析，以定量评估HAIC-L-P方案与单独L-P方案的综合效果。 结果：在我们对八项回顾性队列研究的系统荟萃分析中，HAIC-L-P方案显示OS显著提高，HR为0.54（95%CI：0.45-0.64；p<0.00001），1年和2年总生存率提高。HAIC-L-P组也观察到PFS更佳，HR为0.64（95%CI：0.55-0.75；p<0.0001），1年和2年无进展生存率更高。HAIC-L-P组的缓解率明显更高，ORR风险比为2.15（95%CI：1.84-2.50；p<0.00001），DCR风险比为1.28（95%CI：1.20-1.43；p<0.0001）。HAIC-L-P组3级及以上AE有所增加，呕吐、AST升高、ALT升高、血小板减少、中性粒细胞减少和高胆红素血症的风险比显著。未报告危及生命的AE。 结论：HAIC-L-P方案与增强的肿瘤反应和延长的生存期相关，且不良反应可控，表明其作为uHCC患者可行治疗策略的潜力。 系统评价注册：https://www.crd.york.ac.uk/PROSPERO/，标识符CRD42024594109。
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