title: Efficacy and safety of vascular endothelial growth factor receptor tyrosine kinase inhibitors in the treatment of advanced thyroid cancer: a meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  We performed a systematic review and meta-analysis to determine the efficacy and safety of the US Food and Drug Administration approved vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) in the treatment of advanced thyroid cancer.
  
  
  METHODS
  We included prospective randomized controlled trials that compared VEGFR-TKIs with placebo for advanced thyroid cancer. The endpoints included safety (fatal adverse events [FAEs], treatment discontinuation, and any severe [grade 3 or 4] adverse events [AEs]) and efficacy (objective response rate, progression-free survival, and overall survival). The pooled relative risk (RR) or hazard ratio (HR) was calculated by using either random-effects or fixed-effects models according to the heterogeneity of included studies.
  
  
  RESULTS
  A total of 1,614 advanced thyroid cancer patients from five randomized controlled trials were identified for analysis. Compared with placebo alone, VEGFR-TKIs significantly increased the risk of treatment discontinuation (RR: 3.80, 95% confidence interval [CI]: 2.56-5.65, P<0.001) and any severe AEs (RR: 2.63, 95% CI: 1.72-4.03, P<0.001), but not of FAEs (RR: 1.24, 95% CI: 0.65-2.39, P=0.52). The use of VEGFR-TKIs in advanced thyroid cancer was associated with a significant improvement in objective response rate (RR: 8.73, 95% CI: 1.72-44.4, P=0.009) and progression-free survival (HR: 0.41, 95% CI: 0.27-0.61, P<0.001), with a tendency to improve overall survival (HR: 0.83, 95% CI: 0.68-1.01, P=0.06).
  
  
  CONCLUSIONS
  The use of small-molecule VEGFR-TKIs in advanced thyroid cancer did significantly increase the risk of treatment discontinuation and any severe AEs, but not of FAEs, compared with placebo alone. It is important for physicians to weigh the risk of toxicities as well as the potential survival benefits associated with VEGFR-TKI treatment in advanced thyroid cancer patients.
authors.affiliation: Department of Vascular Thyroid Surgery, Gastrointestinal Vascular Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Province, People's Republic of China.
authors.forename: Wufuer
authors.initials: W
authors.lastname: Yimaer
authors.affiliation: Department of Vascular Thyroid Surgery, Gastrointestinal Vascular Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Province, People's Republic of China.
authors.forename: Aizizi
authors.initials: A
authors.lastname: Abudouyimu
authors.affiliation: Department of Vascular Thyroid Surgery, Gastrointestinal Vascular Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Province, People's Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Vascular Thyroid Surgery, Gastrointestinal Vascular Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Province, People's Republic of China.
authors.forename: Sailike
authors.initials: S
authors.lastname: Magaoweiya
authors.affiliation: Department of Vascular Thyroid Surgery, Gastrointestinal Vascular Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Province, People's Republic of China.
authors.forename: Duman
authors.initials: D
authors.lastname: Bagedati
authors.affiliation: Department of Vascular Thyroid Surgery, Gastrointestinal Vascular Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Province, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wen
keywords: angiogenesis inhibitors; clinical trials; meta-analysis; thyroid cancer; toxicity