title: Risk of treatment-related deaths with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a meta-analysis of 41 randomized controlled trials.
abstract: BACKGROUND
  Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have widely been used in advanced cancer. However, these drugs may also lead to serious adverse events. The present meta-analysis aimed to determine the overall incidence and risk of deaths due to VEGFR-TKIs with more detailed subgroup analysis.
  
  
  METHODS
  PubMed, Web of Science, and Cochrane databases were searched for randomized controlled trials (RCTs) that compared VEGFR-TKIs with non-VEGFR-TKIs in the treatment of solid cancer. Pooled incidence, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included trials.
  
  
  RESULTS
  A total of 14,139 participants from 41 RCTs were enrolled. The pooled incidence of death due to VEGFR-TKIs was 1.9% (95% CI: 1.6%-2.3%) with an OR of 1.85 (95% CI: 1.33-2.58; P<0.01) when compared with control groups. On subgroup analysis, significantly increased risk of death was found in patients with nonsmall-cell lung cancer (OR: 2.37; 95% CI: 1.19-4.73; P=0.01) and colorectal cancer (OR: 2.84; 95% CI: 1.02-7.96; P=0.05). Among different VEGFR-TKIs, sorafenib and sunitinib had significant risk of death when compared with control arms, respectively. VEGFR-TKIs in combination with other antineoplastic agents, but not VEGFR-TKI monotherapy, significantly increased the risk of treatment-related deaths. No heterogeneity was noted across all the prespecified subgroups regarding ORs.
  
  
  CONCLUSIONS
  The present work pointed out a significantly increased risk of death due to VEGFR-TKIs. Close monitoring should be emphasized in patients receiving these drugs.
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Shaodong
authors.initials: S
authors.lastname: Hong
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Zhihuang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Cong
authors.initials: C
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Hou
authors.affiliation: Medical School, University of South China, Hengyang, Hunan, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
keywords: cancer; meta-analysis; treatment-related death; tyrosine kinase inhibitors