Antiangiogenesis therapy in ovarian cancer patients: An updated meta-analysis for 15 randomized controlled trials

BACKGROUND: Antiangiogenesis therapy has been demonstrated to prolong the free survival with tolerable toxicity. However the efficacy of these drugs in overall survival (OS) remains controversial. This study was designed to assess the overall performance of antiangiogenesis therapy in improving the survival of ovary cancer (OC) patients. METHODS: Electronic database of PubMed, Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched to identify relevant clinical randomized control trial (RCTs) assessing the therapeutic value of antiangiogenesis therapy in OC patients during 2011 to 2017. Additionally, abstracts of annual meetings were also conducted. Only English articles were considered. Progression free survival (PFS), OS, and objective response rate (ORR) were obtained from eligible RCTs. The HRs for time-to-event variables and ORs for dichotomous outcomes with their 95% CIs were used for this meta-analysis. All the statistical analyses were carried out by Stata 11.0 software using a fixed or random-models according to heterogeneity. RESULTS: A total of 15 RCTs including 9359 patients were recruited into this meta-analysis. Addition of antiangiogenic agents improved PFS (HR = 0.71, 95% CI 0.62–0.81, P < .001), OS (HR = 0.92, 95% CI 0.86–0.98, P = .008) and ORR (OR = 1.74, 95% CI 1.27–2.39, P = .001) compared to placebo or chemotherapy alone in overall analysis. Antiangiogenic agents prolonged both PFS (HR = 0.58, 95% CI 0.52–0.65, P = .000) and OS (HR=0.84, 95% CI 0.76–0.92, P = .000) in recurrent settings but only PFS in primary settings (HR = 0.88, 95% CI 0.79–0.98, P = .020), longer PFS and OS in both platinum-sensitive recurrent patients (HR = 0.56, 95% CI 0.48–0.64, P = .000, PFS; HR = 0.86, 95% CI 0.76–0.98, P = .027, OS) as well as platinum-resistant recurrent cases (HR = 0.54, 95% CI 0.41–0.71, P = .000, PFS; HR = 0.84, 95% CI 0.71–0.98, P = .029, OS). Throughout therapy improved PFS (HR = 0.66, 95% CI 0.57–0.76, P < .001) and OS (HR = 0.89, 95% CI 0.83–0.96, P = .001). However the maintenance therapy of antiangiogenic agents was irrelevant to a longer PFS or OS. CONCLUSION: Based on the available studies, antiangiogenic agents play an important role in the survival of OC patients. More randomized controlled trials are needed to reach more convinced conclusion.