Angiogenesis Inhibitors for the Treatment of Ovarian Cancer: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials

BACKGROUND: Angiogenesis inhibitors showed activity in ovarian cancer, but preliminary data could not accurately reflect the survival benefit. We thus did a systematic review and meta-analysis of randomized controlled trials to reassess the efficacy and safety of angiogenesis inhibitors combined with chemotherapy for ovarian cancer. METHODS: We searched PubMed, EMBASE, Cochrane, and ClinicalTrials.gov for randomized controlled trials comparing angiogenesis inhibitors containing therapy with conventional chemotherapy alone or no further treatment. Our main outcomes were the progression-free survival (PFS), overall survival (OS), and common adverse events. RESULTS: Fifteen trials were included (N = 8721 participants). For newly diagnosed ovarian cancer, combination treatment with angiogenesis inhibitors and chemotherapy yielded a lower risk of disease progression (hazard ratio [HR], 0.83; 95% confidence interval (CI), 0.71–0.97) and no improved OS (HR, 0.95; 95% CI, 0.86–1.05). In the high-risk progression subgroup, the addition of bevacizumab significantly improved PFS (HR, 0.72; 95% CI, 0.65–0.81) and OS (HR, 0.84; 95%CI, 0.74–0.96). In recurrent patients, the combined HR was 0.58 (95% CI, 0.52–0.65) for PFS, and for OS, the combined HR was 0.86 (95% CI, 0.79–0.94). We found no significant improvement for either PFS (HR, 0.80; 95% CI, 0.63–1.01) or OS (HR, 1.06; 95% CI, 0.88–1.28) in the pure maintenance therapy. In the overall population, angiogenesis inhibitors increased the incidence of gastrointestinal perforation (risk ratio [RR], 2.57; 95% CI, 1.66–3.97), hypertension (RR, 7.60; 95% CI, 2.79–20.70), arterial thromboembolism (RR, 2.27; 95% CI, 1.34–3.84), proteinuria (RR, 4.31; 95% CI, 2.15–8.64), and complication of wound healing (RR, 1.72, 95% CI, 1.12–2.63). CONCLUSIONS: Combination treatment with angiogenesis inhibitors and chemotherapy significantly improved PFS and OS in both patients with high-risk of progression and recurrent ovarian cancer, with an increased incidence of common adverse events. Conversely, we detected no statistically significant survival benefit in the pure maintenance setting. The main limitation of the review is clinical heterogeneity across the studies.