Angiogenesis inhibitors for patients with ovarian cancer: A meta-analysis of 12 randomized controlled trials

Abstract
 
Objectives: To investigate the effects of angiogenesis inhibitors in the treatment for patients with advanced or recurrent ovarian cancer, a meta-analysis was performed and overall survival (OS), progression-free survival (PFS), and toxicity were assessed.
Patients and methods: The PubMed, Embase databases and the Cochrane Central Register of Controlled Trials were searched for publications between January 2000 and June 2015....
Results: Twelve trials in this meta-analysis were divided into 3 groups: 4 trials with VEGF inhibitor (the bevacizumb group), 6 trials with VEGFR inhibitors (the VEGFRIs group), and 2 trials with 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 bevacizumb, 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 toxicity profile differed, VEGFRIs developed common higher incidences of hypertension, diarrhea, and fatigue. More incidences 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.