title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Oncology.
authors.forename: Dianbao
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Cardiac Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan Province, People's Republic of China.
authors.forename: Xianfen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology.
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhao
keywords: anti-VEGF agents; arterial thromboembolic events; meta-analysis; toxicity; venous thromboembolic events