Comparative efficacy and safety of systemic therapy for advanced hepatocellular carcinoma: a systematic review and network meta-analysis

BackgroundIn recent years, there has been rapid development in systemic therapeutic agents for advanced hepatocellular carcinoma. However, most treatment modalities lack head-to-head comparisons, and the distinctions in their efficacy and safety have yet to be elucidated. Consequently, the accurate...

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Main Authors: Di Wu, Binyang Jia, Muyuan Jia, Haitao Zhao, Hong Zhao, Jinxue Zhou
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-12-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2023.1274754/full
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author Di Wu
Binyang Jia
Muyuan Jia
Haitao Zhao
Hong Zhao
Jinxue Zhou
author_facet Di Wu
Binyang Jia
Muyuan Jia
Haitao Zhao
Hong Zhao
Jinxue Zhou
author_sort Di Wu
collection DOAJ
description BackgroundIn recent years, there has been rapid development in systemic therapeutic agents for advanced hepatocellular carcinoma. However, most treatment modalities lack head-to-head comparisons, and the distinctions in their efficacy and safety have yet to be elucidated. Consequently, the accurate selection of a treatment regimen poses a significant challenge for clinicians.MethodsThis study incorporated twenty-three randomized controlled trials, encompassing fifteen first-line and eight second-line treatments, and involving a total of 14,703 patients with advanced hepatocellular carcinoma. Results: In the context of first-line treatment, it was observed that the combination of a PD-1 inhibitor with bevacizumab (1/15) significantly extended overall survival in patients with advanced HCC. Furthermore, PD-1 inhibitors combined with TKIs (1/15) and PD-1 inhibitors combined with bevacizumab (2/15) exhibited enhanced efficacy in reducing the risk of progression-free survival events. In second-line therapy, the network meta-analysis revealed that all investigational agents prolonged progression-free survival in patients with advanced hepatocellular carcinoma when compared to placebo. Cabozantinib ranked first (1/7) in this regard. However, this translated into an overall survival benefit only for cabozantinib, regorafenib, ramucirumab, and pembrolizumab, with regorafenib achieving the highest ranking (1/7).ConclusionIn the treatment of advanced HCC, the immune checkpoint inhibitor combined with bevacizumab regimen and the immune checkpoint inhibitor combined with TKI regimen stand out as the two most effective first-line treatment options. It is noteworthy that, for patients with absolute contraindications to VEGF inhibitors, dual immunotherapy is the preferred choice. For second-line treatment, regorafenib and cabozantinib are identified as the two most effective options.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42023440173.
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spelling doaj.art-c456ff4509644175a81dae7d1d707b732023-12-06T08:09:09ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-12-011310.3389/fonc.2023.12747541274754Comparative efficacy and safety of systemic therapy for advanced hepatocellular carcinoma: a systematic review and network meta-analysisDi Wu0Binyang Jia1Muyuan Jia2Haitao Zhao3Hong Zhao4Jinxue Zhou5Department of Otolaryngology, Head and Neck Surgery, Graduate College of Youjiang Medical University for Nationalities, Baise, Guangxi Zhuang, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Neuro-Oncology, Beijing Arion Cancer Center, Beijing, ChinaDepartment of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Hepatobiliary Surgery, National Cancer Centre/National Clinical Research Centre for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaBackgroundIn recent years, there has been rapid development in systemic therapeutic agents for advanced hepatocellular carcinoma. However, most treatment modalities lack head-to-head comparisons, and the distinctions in their efficacy and safety have yet to be elucidated. Consequently, the accurate selection of a treatment regimen poses a significant challenge for clinicians.MethodsThis study incorporated twenty-three randomized controlled trials, encompassing fifteen first-line and eight second-line treatments, and involving a total of 14,703 patients with advanced hepatocellular carcinoma. Results: In the context of first-line treatment, it was observed that the combination of a PD-1 inhibitor with bevacizumab (1/15) significantly extended overall survival in patients with advanced HCC. Furthermore, PD-1 inhibitors combined with TKIs (1/15) and PD-1 inhibitors combined with bevacizumab (2/15) exhibited enhanced efficacy in reducing the risk of progression-free survival events. In second-line therapy, the network meta-analysis revealed that all investigational agents prolonged progression-free survival in patients with advanced hepatocellular carcinoma when compared to placebo. Cabozantinib ranked first (1/7) in this regard. However, this translated into an overall survival benefit only for cabozantinib, regorafenib, ramucirumab, and pembrolizumab, with regorafenib achieving the highest ranking (1/7).ConclusionIn the treatment of advanced HCC, the immune checkpoint inhibitor combined with bevacizumab regimen and the immune checkpoint inhibitor combined with TKI regimen stand out as the two most effective first-line treatment options. It is noteworthy that, for patients with absolute contraindications to VEGF inhibitors, dual immunotherapy is the preferred choice. For second-line treatment, regorafenib and cabozantinib are identified as the two most effective options.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42023440173.https://www.frontiersin.org/articles/10.3389/fonc.2023.1274754/fullhepatocellular carcinomatargeted therapytyrosine kinase inhibitorsimmune checkpoint inhibitorsfirst-line treatmentsecond-line treatment
spellingShingle Di Wu
Binyang Jia
Muyuan Jia
Haitao Zhao
Hong Zhao
Jinxue Zhou
Comparative efficacy and safety of systemic therapy for advanced hepatocellular carcinoma: a systematic review and network meta-analysis
Frontiers in Oncology
hepatocellular carcinoma
targeted therapy
tyrosine kinase inhibitors
immune checkpoint inhibitors
first-line treatment
second-line treatment
title Comparative efficacy and safety of systemic therapy for advanced hepatocellular carcinoma: a systematic review and network meta-analysis
title_full Comparative efficacy and safety of systemic therapy for advanced hepatocellular carcinoma: a systematic review and network meta-analysis
title_fullStr Comparative efficacy and safety of systemic therapy for advanced hepatocellular carcinoma: a systematic review and network meta-analysis
title_full_unstemmed Comparative efficacy and safety of systemic therapy for advanced hepatocellular carcinoma: a systematic review and network meta-analysis
title_short Comparative efficacy and safety of systemic therapy for advanced hepatocellular carcinoma: a systematic review and network meta-analysis
title_sort comparative efficacy and safety of systemic therapy for advanced hepatocellular carcinoma a systematic review and network meta analysis
topic hepatocellular carcinoma
targeted therapy
tyrosine kinase inhibitors
immune checkpoint inhibitors
first-line treatment
second-line treatment
url https://www.frontiersin.org/articles/10.3389/fonc.2023.1274754/full
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