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Abstract
The efficacy of anti-angiogenic agents (AAAs) in epithelial ovarian cancer (EOC) remains unclear. Therefore, we conducted a systematic review and network meta-analysis (NMA) to synthesize evidence of their comparative effectiveness for improving overall survival (OS) among EOC patients. We searched six databases for randomized controlled trials (RCTs) from their inception to February 2021. We performed an NMA with hazard ratios (HRs) and 95%-confidence intervals (CIs) to evaluate comparative effectiveness among different AAAs in chemotherapy-naïve and recurrent EOC. P-score was used to provide an effectiveness hierarchy ranking. Sensitivity NMA was carried out by focusing on studies that reported high-risk chemotherapy-naïve, platinum-resistant, and platinum-sensitive EOC. The primary outcome was OS. We identified 23 RCTs that assessed the effectiveness of AAAs. In recurrent EOC, concurrent use of trebananib (10 mg/kg) with chemotherapy was likely to be the best option (P-score: 0.88, HR 1.67, 95% CI 0.94; 2.94). The NMA indicated that bevacizumab plus chemotherapy followed by maintenance bevacizumab (P-score: 0.99) and pazopanib combined with chemotherapy (P-score: 0.79) both had the highest probability of being the best intervention for improving OS in high-risk chemotherapy-naïve and platinum-resistant EOC, respectively. AAAs may not play a significant clinical role in non-high-risk chemotherapy-naïve and platinum-sensitive EOC.
Highlights
The efficacy of anti-angiogenic agents (AAAs) in epithelial ovarian cancer (EOC) remains unclear
A total of 2363 publications were identified through the initial literature search, and 1563 studies remained after duplications were excluded
Four randomized controlled trials (RCTs) were conducted in the chemotherapy naïve setting, three in the first-line maintenance setting, and 16 in the recurrent EOC setting
Summary
The efficacy of anti-angiogenic agents (AAAs) in epithelial ovarian cancer (EOC) remains unclear. We identified 23 RCTs that assessed the effectiveness of AAAs. In recurrent EOC, concurrent use of trebananib (10 mg/kg) with chemotherapy was likely to be the best option (P-score: 0.88, HR 1.67, 95% CI 0.94; 2.94). AAAs may not play a significant clinical role in non-high-risk chemotherapy-naïve and platinum-sensitive EOC. The fifth Gynecologic Cancer Intergroup (GCIG) recommended re-categorizing platinum sensitivity based on platinum-free interval (PFI) duration (< 1 month, 1–6 months, 6–12 months, and > 12 months). In EOC, bevacizumab is the only anti-angiogenic agent approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA). The EMA has approved the clinical use of bevacizumab in EOC irrespective of disease state: chemotherapy-naïve[18,19]; platinum-sensitive[3], and platinum-resistant[2] disease
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