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经动脉化疗栓塞联合酪氨酸激酶和免疫检查点抑制剂治疗不可切除肝细胞癌的临床疗效

Clinical benefits of transarterial chemoembolization combined with tyrosine kinase and immune checkpoint inhibitors for unresectable hepatocellular carcinoma.

作者信息

Han Feng, Wang Xiao-Han, Xu Chen-Zhou

机构信息

Department of Gastroenterology, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China.

出版信息

World J Gastrointest Oncol. 2024 Jul 15;16(7):3308-3320. doi: 10.4251/wjgo.v16.i7.3308.

Abstract

BACKGROUND

Combination therapy has emerged as the focus of research for unresectable hepatocellular carcinoma (HCC). In recent years, several studies have explored the clinical efficacy and safety of the combination therapies of transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs).

AIM

To conduct an updated meta-analysis verifying the clinical benefits and adverse effects of the triple combination therapy for unresectable HCC.

METHODS

All eligible cohort, non-randomized controlled, and randomized controlled trial studies from the PubMed, Web of Science, Embase, Cochrane Library, and MedLine databases up to March 20, 2024 were screened for the present meta-analysis. The study endpoints included complete response (CR), objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Stata 16/18 software was used for this meta-analysis, and a value of <0.05 was considered statistically significant.

RESULTS

A total of 29 studies with 1754 patients were included. Among the patients who received the TACE therapy with TKIs and ICIs, the tumor response results revealed a pooled CR, ORR, and DCR of 14% [95%CI (0.11-0.18)], 61% [95%CI (0.55-0.66)], and 85% [95%CI (0.83-0.87)], respectively. In terms of the survival outcomes, the pooled median PFS and OS were 10.25 months [95%CI (9.31-11.18)] and 20.47 months [95%CI (18.98-21.97)], respectively. The pooled prevalence of all-grade AEs during the triple treatment was 90% [95%CI (0.84-0.94)] and that of grade ≥ 3 AEs was 32% [95%CI (0.24-0.42)].

CONCLUSION

The combination therapy of TACE, TKIs, and ICIs exhibits great clinical benefits for unresectable HCC in terms of tumor responses and survival outcomes without increasing the risk of severe AEs.

摘要

背景

联合治疗已成为不可切除肝细胞癌(HCC)研究的焦点。近年来,多项研究探讨了经动脉化疗栓塞术(TACE)与酪氨酸激酶抑制剂(TKIs)及免疫检查点抑制剂(ICIs)联合治疗的临床疗效和安全性。

目的

进行一项更新的荟萃分析,验证不可切除HCC三联联合治疗的临床获益和不良反应。

方法

对截至2024年3月20日来自PubMed、Web of Science、Embase、Cochrane图书馆和MedLine数据库的所有符合条件的队列研究、非随机对照研究和随机对照试验研究进行筛选,用于本荟萃分析。研究终点包括完全缓解(CR)、客观缓解率(ORR)、疾病控制率(DCR)、总生存期(OS)、无进展生存期(PFS)和不良事件(AEs)。本荟萃分析使用Stata 16/18软件,P值<0.05被认为具有统计学意义。

结果

共纳入29项研究,涉及1754例患者。在接受TACE联合TKIs和ICIs治疗的患者中,肿瘤反应结果显示,汇总的CR、ORR和DCR分别为14% [95%CI(0.11 - 0.18)]、61% [95%CI(0.55 - 0.66)]和85% [95%CI(0.83 - 0.87)]。在生存结局方面,汇总的中位PFS和OS分别为10.25个月[95%CI(9.31 - 11.18)]和20.47个月[95%CI(18.98 - 21.97)]。三联治疗期间所有级别的AEs汇总患病率为90% [95%CI(0.84 - 0.94)],≥3级AEs的汇总患病率为32% [95%CI(0.24 - 0.42)]。

结论

TACE、TKIs和ICIs的联合治疗在肿瘤反应和生存结局方面对不可切除HCC显示出巨大的临床获益,且不会增加严重AEs的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7216/11271784/fe0d9133d0a1/WJGO-16-3308-g001.jpg

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