title: Angiogenesis inhibitors for patients with ovarian cancer: a meta-analysis of 12 randomized controlled trials.
abstract: OBJECTIVE
  To investigate the effects of angiogenesis inhibitors in the treatment of patients with advanced or recurrent ovarian cancer, a meta-analysis was performed and overall survival (OS), progression-free survival (PFS), and toxicity were assessed.
  
  
  METHODS
  The PubMed and Embase databases, and the Cochrane Central Register of Controlled Trials were searched for publications between January 2000 and June 2015. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived.
  
  
  RESULTS
  The 12 trials in this meta-analysis were divided into three groups: four trials with a VEGF inhibitor (the bevacizumab group), six trials with VEGFR inhibitors (the VEGFRIs group), and two trials with an angiopoietin inhibitor (the trebananib group). PFS improvement was seen in all groups (HR = 0.61, 95% CI 0.48 to 0.79, P < 0.001 for bevacizumab; HR = 0.71, 95% CI 0.59 to 0.87, P = 0.001 for VEGFRIs; and HR = 0.67, 95% CI 0.62 to 0.72, P < 0.001 for trebananib). Regarding OS, bevacizumab showed a trend of improvement (HR = 0.90, 95% CI 0.80 to 1.01, P = 0.079), VEGFRIs showed no improvement (HR = 0.92, 95% CI 0.75 to 1.11, P = 0.368), and trebananib demonstrated a significant prolongation (HR = 0.81, 95% CI 0.67 to 0.99, P = 0.036). Bevacizumab was associated with more class-specific adverse events (RR = 4.05, 95% CI 1.99 to 8.27, P < 0.001). Although the toxicity profiles differed, VEGFRIs developed common higher incidences of hypertension, diarrhea, and fatigue. A higher incidence of edema was reported in the trebananib group (RR = 2.60, 95% CI 0.84 to 8.00, P = 0.097).
  
  
  CONCLUSIONS
  Anti-angiogenic therapy showed clear PFS benefit with increased toxicity, but its role in OS was undefined for ovarian cancer which emphasized the need for patient selection.
authors.affiliation: a a Department of Medical Oncology , Affiliated Shantou Hospital of Sun Yat-sen University , Shantou , Guangdong , China.
authors.forename: Xuyuan
authors.initials: X
authors.lastname: Li
authors.affiliation: b b Department of Good Clinical Practice , Cancer Hospital of Shantou University Medical College , Shantou , Guangdong , China.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Zhu
authors.affiliation: c c Cancer Research Lab, Cancer Hospital of Shantou University Medical College , Shantou , Guangdong , China.
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Hong
authors.affiliation: d d Department of Medical Oncology , First affiliated Hospital of Shantou University Medical College , Shantou , Guangdong , China.
authors.forename: Haoquan
authors.initials: H
authors.lastname: Cai
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic
chemical_list: D020533:Angiogenesis Inhibitors; D047428:Protein Kinase Inhibitors; D000068258:Bevacizumab
keywords: Angiogenesis; Meta-analysis; Ovarian cancer; Toxicity