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Risk of venous and arterial thromboembolic events associated with anti-VEGF agents in advanced non-small-cell lung cancer: a meta-analysis and systematic review

Authors Zhang D, Zhang X, Zhao C

Received 6 January 2016

Accepted for publication 31 March 2016

Published 21 June 2016 Volume 2016:9 Pages 3695—3704


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Professor Min Li

Dianbao Zhang,1,* Xianfen Zhang,2,* Chunling Zhao1

1Department of Medical Oncology, 2Department of Cardiac Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan Province, People’s Republic of China

*These authors contributed equally to this work

Aims: To assess the incidence and risk of arterial and venous thromboembolic events (ATEs and VTEs) associated with antivascular endothelial growth factor (VEGF) agents, including VEGF receptor-tyrosine kinase inhibitors and VEGF monoclonal antibodies, in advanced non-small-cell lung cancer (NSCLC) patients.
Methods: We performed a broad search of PubMed for relevant trials. Prospective randomized trials evaluating therapy with or without anti-VEGF agents in patients with advanced NSCLC were included for analysis. Data on VTEs and ATEs were extracted. The overall incidence, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were pooled according to the heterogeneity of included trials.
Results: A total of 13,436 patients from 23 trials were included for analysis. Our results showed that anti-VEGF agents significantly increased the risk of developing high-grade ATEs (Peto OR: 1.44, 95% CI: 1.00–2.07, P=0.048), but not for all-grade ATEs (Peto OR: 0.94, 95% CI: 0.56–1.59, P=0.82) compared with controls. Additionally, no increased risk of all-grade and high-grade VTEs (Peto OR: 0.94, 95% CI: 0.67–1.31, P=0.71 and Peto OR: 0.95, 95% CI: 0.73–1.22, P=0.67, respectively) was observed in advanced NSCLC patients receiving anti-VEGF agents.
Conclusion: The use of anti-VEGF agents in advanced NSCLC patients significantly increased the risk of high-grade ATEs, but not for VTEs. Clinicians should be aware of the risk of severe ATEs with administration of these drugs in advanced NSCLC patients.

Keywords: anti-VEGF agents, toxicity, arterial thromboembolic events, venous thromboembolic events, meta-analysis

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