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肝动脉灌注化疗增强乐伐替尼和PD - 1抑制剂治疗晚期肝细胞癌的疗效:一项荟萃分析和试验序贯分析

Hepatic arterial infusion chemotherapy enhances the efficacy of lenvatinib and PD-1 inhibitors for advanced hepatocellular carcinoma: A meta-analysis and trial sequential analysis.

作者信息

Yu Jiahui, Li Yong, Yu Jinxin, Yang Yuting, Chen Yimiao, Yi Pengsheng

机构信息

Department of Hepato-biliary-pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, PR China.

North Sichuan Medical College, Nanchong, Sichuan, 637000, PR China.

出版信息

Eur J Surg Oncol. 2025 Mar;51(3):109573. doi: 10.1016/j.ejso.2025.109573. Epub 2025 Jan 6.

DOI:10.1016/j.ejso.2025.109573
PMID:39793379
Abstract

BACKGROUND

Hepatic arterial infusion chemotherapy (HAIC) was an effective treatment for advanced hepatocellular carcinoma (HCC), and its effectiveness in combination with targeted immunotherapy regimens was controversial. This meta-analysis was performed to evaluate the efficacy of adding HAIC to lenvatinib in combination with programmed death-1 (PD-1) inhibitors.

METHODS

Literature related to the efficacy of HAIC in combination with lenvatinib plus PD-1 inhibitors in the treatment of advanced HCC was searched through PubMed, Cochrane Library, Embase, and Web of Science databases. TSA was used to control for the risk of random error and assess whether the meta-analysis evidence was conclusive.

RESULTS

Eight relevant papers with a total of 1244 patients. Compared with the L-P treatment group, the H-L-P treatment group significantly prolonged OS (hazard ratio [HR] 2.11 [95 % confidence interval (CI) 1.82-2.44]; p < 0.001) and PFS (HR 1.91 [95 % CI 1.67-2.17]; p < 0.001) and improved ORR (risk ratio [RR] 2.20 [95 % CI 1.74-2.78]; p < 0.001) and DCR (RR 1.28 [95 % CI 1.15-1.42]; p < 0.001) in patients with advanced HCC. TSA analysis indicated that further trials were unnecessary, preliminary positive results were promptly obtained. Prognostic factor analysis demonstrated that extrahepatic metastasis were common independent risk factor for OS and PFS. The rate of adverse events (AEs) was higher in the H-L-P treatment group than in the L-P treatment group.

CONCLUSION

HAIC combined with lenvatinib plus PD-1 inhibitors markedly extended OS and PFS, particularly in patients without extrahepatic metastases. Furthermore, it markedly enhanced ORR and DCR in patients with HCC.

摘要

背景

肝动脉灌注化疗(HAIC)是晚期肝细胞癌(HCC)的一种有效治疗方法,其与靶向免疫治疗方案联合应用的有效性存在争议。本荟萃分析旨在评估在乐伐替尼联合程序性死亡受体1(PD-1)抑制剂的基础上加用HAIC的疗效。

方法

通过PubMed、Cochrane图书馆、Embase和Web of Science数据库检索与HAIC联合乐伐替尼加PD-1抑制剂治疗晚期HCC疗效相关的文献。采用累积Meta分析(TSA)控制随机误差风险,并评估荟萃分析证据是否确凿。

结果

8篇相关论文,共纳入1244例患者。与乐伐替尼联合PD-1抑制剂治疗组(L-P治疗组)相比,HAIC联合乐伐替尼联合PD-1抑制剂治疗组(H-L-P治疗组)显著延长了晚期HCC患者的总生存期(OS,风险比[HR] 2.11 [95%置信区间(CI)1.82 - 2.44];p < 0.001)和无进展生存期(PFS,HR 1.91 [95% CI 1.67 - 2.17];p < 0.001),并提高了客观缓解率(ORR,风险比[RR] 2.20 [95% CI 1.74 - 2.78];p < 0.001)和疾病控制率(DCR,RR 1.28 [95% CI 1.15 - 1.42];p < 0.001)。TSA分析表明无需进一步试验,已迅速获得初步阳性结果。预后因素分析显示,肝外转移是OS和PFS常见的独立危险因素。H-L-P治疗组的不良事件(AE)发生率高于L-P治疗组。

结论

HAIC联合乐伐替尼加PD-1抑制剂显著延长了OS和PFS,尤其是在无肝外转移的患者中。此外,它还显著提高了HCC患者的ORR和DCR。

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引用本文的文献

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