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Fatal adverse events with molecular targeted agents in the treatment of advanced hepatocellular carcinoma: a meta-analysis of randomized controlled trials

Authors Li X, Wan J, Wu Z, Tu J, Hu Y, Wu S, Lou L

Received 8 September 2017

Accepted for publication 10 April 2018

Published 18 September 2018 Volume 2018:12 Pages 3043—3049


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Sukesh Voruganti

Xiaofei Li,1 Jia Wan,2 Zhenping Wu,3 Juncai Tu,1 Yongtao Hu,1 Shuang Wu,1 Lianqing Lou1

1Department of Infectious Diseases, Yiwu Central Hospital, Yiwu, China; 2The First Hospital of Nanchang, Nanchang, China; 3Gastroenterology Department, Jinhua Central Hospital, Jinhua, China

Aims: Concerns have increased about the risk of fatal adverse events (FAEs) associated with molecular targeted agents (MTAs) in the treatment of advanced hepatocellular carcinoma (HCC). The purpose of this study is to investigate the overall incidence and risk of FAEs in advanced HCC with administration of MTAs by using a meta-analysis of available clinical trials.
Materials and methods: Electronic databases were searched for relevant articles before March 2017. Eligible studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Pooled incidence, Peto ORs and 95% CIs were calculated according to the heterogeneity of selected studies.
Results: A total of 4,716 HCC participants from 10 randomized controlled trials (RCTs) were finally considered for this meta-analysis. The pooled incidence of death due to MTAs was 2.1% (95% CI 1.6%–2.8%) with a Peto OR of 1.79 (95% CI 1.07–3.01; p=0.027) in comparison with controlled groups. Subgroup analysis according to biological agents showed that brivanib treatment in HCC patients significantly increased the risk of developing FAEs (Peto OR 3.97; 95% CI 1.17–13.51; p=0.028) but not for sorafenib (Peto OR 1.78; 95% CI 0.54–5.89; p=0.34) and other MTAs (Peto OR 1.43; 95% CI 0.75–2.76; p=0.28). Sensitive analysis showed that the pooled results were influenced by removing each single trial. The most common causes of FAEs were hepatic failure (22.2%) and hemorrhage (13.3%), respectively.
Conclusion: Clinicians should be aware of the risks of FAEs during the administration of MTAs in advanced HCC patients, especially for patients with abnormal liver function. However, the use of sorafenib remains justified in its approved indications due to their potential survival benefits and limited toxicities.

Keywords: liver cancer, clinical trials, novel molecular agents

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