Retrospective Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2024; 30(4): 318-331
Published online Jan 28, 2024. doi: 10.3748/wjg.v30.i4.318
Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis
Yu-Zhe Cao, Guang-Lei Zheng, Tian-Qi Zhang, Hong-Yan Shao, Jia-Yu Pan, Zi-Lin Huang, Meng-Xuan Zuo
Yu-Zhe Cao, Guang-Lei Zheng, Tian-Qi Zhang, Hong-Yan Shao, Jia-Yu Pan, Zi-Lin Huang, Meng-Xuan Zuo, Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
Yu-Zhe Cao, Guang-Lei Zheng, Tian-Qi Zhang, Hong-Yan Shao, Jia-Yu Pan, Zi-Lin Huang, Meng-Xuan Zuo, Department of Minimally Invasive Interventional Therapy, State Key Laboratory of Oncology in South China, Guangzhou 510060, Guangdong Province, China
Yu-Zhe Cao, Guang-Lei Zheng, Tian-Qi Zhang, Hong-Yan Shao, Jia-Yu Pan, Zi-Lin Huang, Meng-Xuan Zuo, Department of Minimally Invasive Interventional Therapy, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou 510060, Guangdong Province, China
Co-first authors: Yu-Zhe Cao and Guang-Lei Zheng.
Co-corresponding authors: Zi-Lin Huang and Meng-Xuan Zuo.
Author contributions: Cao YZ, Zheng GL, Zuo MX and Huang ZL participated equally in conceptualization; Cao YZ, Zuo MX and Zheng GL made great contribution in the in the data curation, formal analysis, methodology and investigation; Zhang TQ, Shao HY and Pan JY has participated in the investigation and the validation; The project administration and supervision were accomplished by Huang ZL and Zuo MX; Cao YZ and Zheng GL had finished the original draft; Zuo MX and Huang ZL has been responsible for the review and editing; All authors have provided final approval of the manuscript version to be submitted for publication. Cao YZ and Zheng GL, contributed equally to this work and share first authorship for their contribution in conceptualization, data curation, formal analysis, methodology, investigation and draft writing. Huang ZL and Zuo MX, contributed equally to this work and are co-corresponding authors for their contribution in conceptualization, project administration, supervision, revision and approvement for final edition of the manuscript.
Supported by Natural Science Foundation of Guangdong Province, No. 2020A1515011539.
Institutional review board statement: This study was reviewed and approved by the Sun Yat-sen University Cancer Center Ethics Committee. Informed consent was waived due to the retrospective nature of the analysis.
Informed consent statement: Informed consent was waived due to the retrospective nature of the analysis, which has been approved by Ethic Committee of Sun Yat-sen University Cancer Center.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets of the manuscript is available from the corresponding authors at Sun Yat-sen University Cancer Center Research Data Deposit repository (https://www.researchdata.org.cn/). Consent was not obtained but the presented data are anonymized and risk of identification is low.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Meng-Xuan Zuo, MD, Attending Doctor, Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Yuexiu District, Guangzhou 510060, Guangdong Province, China. zuomx@sysucc.org.cn
Received: November 1, 2023
Peer-review started: November 1, 2023
First decision: December 4, 2023
Revised: December 11, 2023
Accepted: January 8, 2024
Article in press: January 8, 2024
Published online: January 28, 2024
Processing time: 85 Days and 21.1 Hours
Abstract
BACKGROUND

Hepatic arterial infusion chemotherapy (HAIC) has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma (uHCC). HAIC-based treatment showed great potential for treating uHCC. However, large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.

AIM

To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors, programmed cell death of protein 1 (PD-1) and its ligand (PD-L1) blockers (triple therapy) under real-world conditions.

METHODS

Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis. Study-level pooled analyses of hazard ratios (HRs) and odds ratios (ORs) were performed. This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades (AIPB) at Sun Yat-sen University Cancer Center from January 2018 to April 2023. Propensity score matching (PSM) was performed to balance the bias between the groups. The Kaplan-Meier method and cox regression were used to analyse the survival data, and the log-rank test was used to compare the suvival time between the groups.

RESULTS

A total of 13 randomized controlled trials were included. HAIC alone and in combination with sorafenib were found to be effective treatments (P values for ORs: HAIC, 0.95; for HRs: HAIC + sorafenib, 0.04). After PSM, 176 HCC patients were included in the analysis. The triple therapy group (n = 88) had a longer median overall survival than the AIPB group (n = 88) (31.6 months vs 14.6 months, P < 0.001) and a greater incidence of adverse events (94.3% vs 75.4%, P < 0.001).

CONCLUSION

This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC. Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.

Keywords: Unresectable hepatocellular carcinoma; Hepatic arterial infusion chemotherapy; Angiogenesis inhibitors; Programmed cell death protein 1; Programmed death ligand 1

Core Tip: The network meta-analysis showed the treatment based on hepatic arterial infusion chemotherapy (HAIC) had the best efficacy on unresectable hepatocellular carcinoma (uHCC). The retrospective, relatively large-scale study suggested HAIC combined with angiogenesis inhibitors and programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) blockers could improve the uHCC patients’ prognosis. After propensity score matching, it demonstrated that triple therapy was able to prolong the uHCC patients’ survival than angiogenesis inhibitors and PD-1/PD-L1 blockers.