title: Treatment-related mortality with aflibercept in cancer patients: a meta-analysis.
abstract: OBJECTIVE
  Aflibercept, a fully humanized vascular endothelial growth factor (VEGF)-targeted agent, has emerged as an effective therapy in the treatment of various solid tumors. We carried out an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in cancer patients treated with aflibercept.
  
  
  METHODS
  We searched databases such as PubMed and Web of Science, and abstracts presented at the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) meetings for records up to August 2013 to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating aflibercept in cancer patients with adequate data on FAEs. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR) and 95 % confidence intervals (CIs) by using either random effects or fixed-effect models according to the heterogeneity of included studies.
  
  
  RESULTS
  A total of 3,060 patients with a variety of solid tumors from ten clinical trials were included in our analysis. The overall incidence of FAEs associated with aflibercept was 5.1 % (95%CI: 3.8-6.8 %). The use of aflibercept significantly increased the risk of FAEs compared to patients treated with control medication (OR 1.81, 95 % CI: 1.20-2.72, p = 0.004). Additionally, the most common causes of FAEs were infection (38.8 %), hemorrhage (5.9 %) and GI perforation (5.9 %), respectively.
  
  
  CONCLUSIONS
  With available evidence, the use of aflibercept is associated with an increased risk of FAEs compared to controls. Further studies are still needed to investigate this association. In the appropriate clinical scenario, the use of aflibercept remains justified in its approved indications.
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan road, Shanghai, 200233, China.
authors.forename: Wei-Xiang
authors.initials: WX
authors.lastname: Qi
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Tang
authors.forename: Zan
authors.initials: Z
authors.lastname: Shen
authors.forename: Yang
authors.initials: Y
authors.lastname: Yao
mesh_terms: D000368:Aged; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology*; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011446:Prospective Studies; D040262:Receptors, Vascular Endothelial Growth Factor / Q000009:adverse effects* / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects* / Q000627:therapeutic use*; D012306:Risk
chemical_list: D011993:Recombinant Fusion Proteins; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor