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Adverse Events of Immune Checkpoint Inhibitor-Based Therapies for Unresectable Hepatocellular Carcinoma in Prospective Clinical Trials: A Systematic Review and Meta-analysis
Abstract
<jats:p>Introduction: To investigate the incidence and spectrum of adverse events
in unresectable hepatocellular carcinoma (HCC) patients treated with immune checkpoint
inhibitors (ICIs) or ICI-based combinations.
Methods: The study protocol was prospectively registered on PROSPERO (CRD42022319255).
We searched PubMed, EMBASE, and the Cochrane Library for published clinical trials
from database inception to April 22, 2022. Studies that included at least one group
of unresectable HCC patients treated with ICIs or ICI-based combinations and reported
the incidence or spectrum of treatment-related adverse events (trAEs) or immune-related
adverse events (irAEs) were eligible. The incidence and spectra of all-grade and grade
≥3 trAEs were the primary outcomes. The profiles of irAEs, the incidence of trAEs
leading to treatment discontinuation, and treatment-related mortalities were additional
outcomes. We applied random-effects models to pool the incidence and spectra of adverse
events. Subgroup analyses and meta-regression were performed.
Results: The literature search identified 2464 records. Twenty studies (4146 participants
with HCC) met the eligibility criteria. The pooled incidences of all-grade trAEs,
grade ≥3 trAEs, all-grade irAEs, and grade≥3 irAEs were 80.1% (95% CI 73.8-85.2),
35.4% (95% CI 27.2-44.6), 31.1% (95% CI 21.0-43.5), and 6.6% (95% CI 3.6-11.8), respectively.
ICIs plus oral targeted agents (all-grade OR=17.07, 95% CI 6.05-48.16, P<0.001;
grade ≥3 OR=9.35, 95% CI 4.53-19.29, P<0.001) and ICIs plus intravenous targeted
agents (all-grade OR=4.91, 95% CI 1.80-13.42, P=0.003; grade ≥3 OR=4.21, 95% CI 1.42-12.48,
P=0.012) were associated with increased trAEs compared with monotherapy. The all-grade
trAEs with the highest pooled incidences were reactive capillary endothelial proliferation
(49.2%, 95% CI 26.3-72.3), neutropenia (34.6%, 95% CI 17.1-57.5), and proteinuria
(32.8%, 95% CI 19.8-49.2). The grade ≥3 trAEs with highest pooled incidences were
hypertension (11.1%, 95% CI 4.0-29.0), neutropenia (10.5%, 95% CI 7.0-15.4), and aspartate
aminotransferase increased (7.7%, 95% CI 6.3-9.4). The pooled incidence of trAEs leading
to treatment discontinuation was 8.0% (95% CI 6.0-10.5), and the overall incidence
of treatment-related mortalities was 1.1%.
Conclusions: This study comprehensively summarized the incidence and spectrum of trAEs
in unresectable HCC patients receiving ICIs or ICI-based combinations in clinical
trials. The results from this study will provide a useful reference to guide clinical
practice.</jats:p>
Type
Journal articlePermalink
https://hdl.handle.net/10161/26442Published Version (Please cite this version)
10.1159/000528698Publication Info
Zhang, Yizhou; Wang, Minghao; Chen, Qichen; Deng, Yiqiao; Chen, Jinghua; Dai, Yimin;
... Cai, Jianqiang (n.d.). Adverse Events of Immune Checkpoint Inhibitor-Based Therapies for Unresectable Hepatocellular
Carcinoma in Prospective Clinical Trials: A Systematic Review and Meta-analysis. Liver Cancer. 10.1159/000528698. Retrieved from https://hdl.handle.net/10161/26442.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Sheng Luo
Professor of Biostatistics & Bioinformatics

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