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Published in: Journal of Cancer Research and Clinical Oncology 5/2022

01-05-2022 | Hepatocellular Carcinoma | Original Article – Clinical Oncology

The efficacy of immune checkpoint inhibitors in advanced hepatocellular carcinoma: a meta-analysis based on 40 cohorts incorporating 3697 individuals

Authors: Rixiong Wang, Nan Lin, Binbin Mao, Qing Wu

Published in: Journal of Cancer Research and Clinical Oncology | Issue 5/2022

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Abstract

Background

This study was designed to investigate the efficacy and safety of immune checkpoint inhibitors (ICIs) in advanced hepatocellular carcinoma (HCC).

Methods

Electronic databases were scanned to identify relevant trials. The primary endpoints were overall survival (OS), progression-free survival (PFS), and their prognostic factors. Stratified analyses were accomplished on ICIs agent and evaluation criteria.

Results

Totally, 3697 individuals from 40 cohorts were recruited. For patients treated with ICIs, the pooled median time to progression (TTP) was 8.0 months, median PFS 4.9 months, and median OS 12.0 months; the pooled median PFS and OS of ICIs plus anti-vascular endothelial growth factor (VEGF) agents (PFS: 6.3 months, OS: 16.4 months) were longer than those of ICIs alone. Furthermore, Child–Pugh stage (HR = 1.37, P = 0.0123) and Eastern Cooperative Oncology Group (ECOG) (HR = 1.40, P = 0.0016) were prognostic factors for PFS. Hepatitis C virus (HCV) (HR = 0.71, P = 0.0356), Alpha-fetoprotein (AFP) (HR = 1.17, P < 0.0001), Child–Pugh stage (HR = 1.58, P < 0.0001), Barcelona Clinic Liver Cancer (BCLC) stage (HR = 1.23, P = 0.0005), ECOG (HR = 1.50, P = 0.0012), portal vein invasion (HR = 1.32, P = 0.0053), extrahepatic metastasis (HR = 0.84, P = 0.0047), best response (HR = 0.58, P < 0.0001), and neutrophil-to-lymphocyte ratio (NLR) (HR = 1.23, P = 0.0451) were the prognostic factors for OS. According to both RECIST 1.1 and mRECIST, the objective response rate (ORR) and disease control rate (DCR) rate of ICIs plus anti-VEGF agents were better than those of ICIs alone. The overall rate of any grade adverse events (AEs) was 0.76 (95% CI 0.61–0.89), grade 3 or higher AEs was 0.28 (95% CI 0.15–0.42), and the rate of AEs leading to treatment discontinuation was 0.09 (95% CI 0.06–0.12).

Conclusions

The ICIs was promising in HCC with good efficacy and tolerated toxicity. Compared with ICIs monotherapy, the joint application of ICIs and anti-VEGF agents can contribute a lot more benefits to the survival of patients according to clinical practices.
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Literature
go back to reference Gonda K, Shibata M, Kanke Y, Yazawa T, Takenoshita S (2013) Circulating myeloid-derived suppressor cells (MDSC) and correlation to poor prognosis, Th2- polarization, inflammation, and nutritional damages in patients with gastric cancer. J Clin Oncol 31(15 Suppl):3063CrossRef Gonda K, Shibata M, Kanke Y, Yazawa T, Takenoshita S (2013) Circulating myeloid-derived suppressor cells (MDSC) and correlation to poor prognosis, Th2- polarization, inflammation, and nutritional damages in patients with gastric cancer. J Clin Oncol 31(15 Suppl):3063CrossRef
go back to reference Kuo HY, Chiang NJ, Chuang CH et al (2020) Impact of immune checkpoint inhibitors with or without a combination of tyrosine kinase inhibitors on organ-specific efficacy and macrovascular invasion in advanced hepatocellular carcinoma. Oncol Res Treat 43(5):211–220. https://doi.org/10.1159/000505933CrossRefPubMed Kuo HY, Chiang NJ, Chuang CH et al (2020) Impact of immune checkpoint inhibitors with or without a combination of tyrosine kinase inhibitors on organ-specific efficacy and macrovascular invasion in advanced hepatocellular carcinoma. Oncol Res Treat 43(5):211–220. https://​doi.​org/​10.​1159/​000505933CrossRefPubMed
Metadata
Title
The efficacy of immune checkpoint inhibitors in advanced hepatocellular carcinoma: a meta-analysis based on 40 cohorts incorporating 3697 individuals
Authors
Rixiong Wang
Nan Lin
Binbin Mao
Qing Wu
Publication date
01-05-2022
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 5/2022
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-021-03716-1

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