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阿替利珠单抗联合贝伐单抗及乐伐替尼作为晚期肝细胞癌一线治疗的系统评价和荟萃分析。

Atezolizumab plus bevacizumab lenvatinib as first-line therapy for advanced hepatocellular carcinoma: A systematic review and meta-analysis.

作者信息

Giri Suprabhat, Angadi Sumaswi, Vaidya Arun, Singh Ankita, Roy Akash, Sundaram Sridhar

机构信息

Nizam's Institute of Medical Sciences, India.

Seth GS Medical College and KEM Hospital, India.

出版信息

Clin Exp Hepatol. 2023 Sep;9(3):228-235. doi: 10.5114/ceh.2023.130748. Epub 2023 Sep 3.

Abstract

AIM OF THE STUDY

Studies comparing atezolizumab plus bevacizumab (ATE/BEV) vs. lenvatinib (LEN) for advanced hepatocellular carcinoma (aHCC) have shown conflicting results. With this background, we aimed to collate the available evidence comparing ATE/BEV and LEN in aHCC.

MATERIAL AND METHODS

A comprehensive search of three databases was conducted from inception to November 2022 for studies comparing ATE/BEV with LEN for managing aHCC. Results were presented with their 95% confidence intervals (95% CI) as the hazard ratio (HR) for time-to-event outcomes or odds ratios (OR) for dichotomous outcomes.

RESULTS

A total of 8 studies were included. On analysis of matched cohorts, there was no difference in the objective response rate (ORR) (adjusted odds ratio [aOR] = 1.15, 95% CI: 0.83-1.61) or disease control rate (DCR) (aOR = 0.83, 95% CI: 0.49-1.38) between groups. Three studies reported a significantly longer progression-free survival (PFS) with ATE/LEN, while one reported a longer PFS with LEN. The adjusted hazard ratio (aHR) for PFS available from three studies was comparable (HR = 1.06, 95% CI: 0.75-1.50). Data were insufficient to carry out a formal analysis for overall survival (OS), but none of the studies reported any difference in OS. On comparison of overall adverse events (AE) and ≥ grade 3 AE, there was no difference in the overall analysis, but higher risk of AE with LEN on sensitivity analysis.

CONCLUSIONS

Based on the currently available literature, LEN was found to be non-inferior to ATE/BEV in terms of ORR, DCR, and PFS. However, LEN may be associated with a higher incidence of AEs. Further head-to-head trials are required to demonstrate the superiority of ATE/BEV over LEN.

摘要

研究目的

比较阿替利珠单抗联合贝伐单抗(ATE/BEV)与乐伐替尼(LEN)治疗晚期肝细胞癌(aHCC)的研究结果相互矛盾。在此背景下,我们旨在整理比较ATE/BEV和LEN治疗aHCC的现有证据。

材料与方法

对三个数据库进行全面检索,检索时间从数据库建立至2022年11月,以查找比较ATE/BEV与LEN治疗aHCC的研究。结果以95%置信区间(95%CI)表示,事件发生时间结局的风险比(HR)或二分结局的比值比(OR)。

结果

共纳入8项研究。对匹配队列进行分析时,两组间的客观缓解率(ORR)(调整后比值比[aOR]=1.15,95%CI:0.83-1.61)或疾病控制率(DCR)(aOR=0.83,95%CI:0.49-1.38)无差异。三项研究报告ATE/LEN组的无进展生存期(PFS)显著更长,而一项研究报告LEN组的PFS更长。三项研究提供的PFS调整后风险比(aHR)具有可比性(HR=1.06,95%CI:0.75-1.50)。数据不足以对总生存期(OS)进行正式分析,但没有研究报告OS有任何差异。在比较总体不良事件(AE)和≥3级AE时,总体分析无差异,但敏感性分析显示LEN发生AE的风险更高。

结论

基于目前的文献,LEN在ORR、DCR和PFS方面不劣于ATE/BEV。然而,LEN可能与更高的AE发生率相关。需要进一步的头对头试验来证明ATE/BEV优于LEN。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3305/10544063/f49dc329f85e/CEH-9-51310-g001.jpg

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