Risk of venous and arterial thromboembolic events associated with tyrosine kinase inhibitors in advanced thyroid cancer: a meta-analysis and systematic review

Yang Bai _, Jing-Yan Li, Jie Li, Bo Zhang, Yong-Hong Liu, Bu-Yong Zhang and Jian Jing

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Oncotarget. 2019; 10:4205-4212. https://doi.org/10.18632/oncotarget.24599

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Yang Bai1,*, Jing-Yan Li2,*, Jie Li1, Bo Zhang1, Yong-Hong Liu1, Bu-Yong Zhang1 and Jian Jing1

1Department of Thyroid Surgery, Cangzhou Central Hospital, Cangzhou, Hebei, China

2Department of Ultrasonography, Cangzhou Hospital of Integrated TCM-WM, Cangzhou, Hebei, China

*These authors contributed equally to this work

Correspondence to:

Yang Bai, email: [email protected]

Keywords: tyrosine kinase inhibitors; toxicity; arterial thromboembolic events; venous thromboembolic events; meta-analysis

Received: September 30, 2017     Accepted: November 13, 2017     Epub: February 26, 2018     Published: June 25, 2019


Aims: To assess the incidence and risk of arterial and venous thromboembolic events (ATEs and VTEs) associated with tyrosine kinase inhibitors (TKIs) in advanced thyroid cancer patients.

Materials and Methods: We comprehensively searched EMBASE, Pubmed, and Cochrane Library for relevant trials. Prospective clinical trials evaluating the role of TKIs alone in advanced thyroid cancer patients were included for analysis. Data on high-grade VTEs and ATEs were extracted. The pooled incidence, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were pooled according to the heterogeneity of included trials.

Results: A total of 1,781 patients from 12 trials, including four randomized controlled trials and eight phase II single arm trials, were included for analysis. Our results showed that the overall incidence of high-grade ATEs and VTEs associated with TKIs were 1.4% and 3.3%, and TKIs treatment in advanced TCs patients significantly increased the risk of developing high-grade ATEs (Peto OR 4.72, 95% CI: 1.18–18.95, p = 0.029), but not for high-grade VTEs (Peto OR 1.36, 95% CI: 0.51–3.64, p = 0.54) when compared to placebo. The most common specific causes of ATEs were myocardial infarction (28.6%) and ischemic cerebrovascular events (21.4%), respectively.

Conclusions: TKIs treatment in advanced thyroid cancer significantly increases the risk of developing high-grade ATEs but not for VTEs. Clinicians should be cautious about the risk of severe ATEs associated with TKIs to maximize the benefits and minimize the toxicities.

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