title: The role of vascular epithelial growth factor receptor-tyrosine kinase inhibitors in the treatment of advanced breast cancer: a meta-analysis of 12 randomized controlled trials.
abstract: OBJECTIVE
  To perform a systematic review and meta-analysis of randomized controlled trials to determine the efficacy and toxicity of approved vascular epithelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) in advanced breast cancer.
  
  
  METHODS
  A comprehensive literature search for studies published up to August 2013 was performed. The endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3 or 4 adverse event (AEs). The pooled hazard ratio (HR) or relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials.
  
  
  RESULTS
  Twelve randomized controlled trials involved 3256 patients were ultimately identified. The intention to treatment (ITT) analysis demonstrated that VEGFR-TKI therapy significantly improved ORR (RR 1.14, 95% CI: 1.03-1.28, p = 0.016), but it did not translate into benefits in PFS (HR 0.99, 95% CI: 0.81-1.22, p = 0.93) and OS (HR 1.11, 95% CI 0.99-1.24, p = 0.084) when compared to non-VEGFR-TKI therapy. Additionally, a higher incidence of grade 3 or 4 anemia, neutropenia, thrombocytopenia, diarrhea, hand-foot syndrome and fatigue was observed in VEGFR-TKI-based therapy.
  
  
  CONCLUSIONS
  The VEGFR-TKI-based therapy offered a significant improvement in ORR in patients with advanced breast cancer but did not benefit PFS and OS. With present available data from randomized clinical trials, we were still unable to clearly set the role of VEGFR-TKIs in the treatment of metastatic breast cancer (MBC).
authors: Department of Breast Surgery, Affiliated Hospital of Guangdong Medical College , Zhanjiang, Guangdong , China.
authors: Jianwen
authors: J
authors: Li
authors: Shengchao
authors: S
authors: Huang
authors: Wanting
authors: W
authors: Zheng
authors: Hongfei
authors: H
authors: Ding
authors: Yuanqi
authors: Y
authors: Zhang
authors: Shuichuan
authors: S
authors: Huang
authors: Zhi
authors: Z
authors: Zhang
authors: Baoying
authors: B
authors: Chen
authors: Zhongzeng
authors: Z
authors: Liang
authors: Gan
authors: G
authors: He
authors: Xiongsheng
authors: X
authors: Xiao
authors: Siyi
authors: S
authors: Li
authors: Tuo
authors: T
authors: Xu
authors: Xiaodong
authors: X
authors: Chen
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D012307:Risk Factors
chemical_list: D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor