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A comprehensive systematic review and network meta-analysis: the role of anti-angiogenic agents in advanced epithelial ovarian cancer.

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.

SUBMITTER: Helali AE

PROVIDER: S-EPMC8907284 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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A comprehensive systematic review and network meta-analysis: the role of anti-angiogenic agents in advanced epithelial ovarian cancer.

Helali Aya El AE Wong Charlene H L CHL Choi Horace C W HCW Chan Wendy W L WWL Dickson Naomi N Siu Steven W K SWK Chan Karen K KK Ngan Hextan Y S HYS Ngan Roger K C RKC Kennedy Richard D RD

Scientific reports 20220309 1

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 eff ...[more]

PMID: 35264616

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Project description:Introduction: Ovarian cancer is a significant contributor to gynecological cancer-related mortality, necessitating innovative treatment strategies. This systematic review and meta-analysis aimed to assess the efficacy and safety of combining PARP inhibitors with anti-angiogenic agents (AAAs) in the treatment of ovarian cancer. Methods: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered on PROSPERO (CRD42022319461). A systematic search of three electronic databases, including MEDLINE (via PubMed), EMBASE, and Cochrane Library was conducted to identify relevant randomized controlled trials (RCT) that evaluated the efficacy and safety of the combination therapy. Subgroup analyses were based on BRCA mutation status. Meta-analysis was conducted to estimate pooled hazard ratios (HR) and risk ratios (RR) for progression-free survival (PFS) and adverse events, respectively. The combination therapy was compared to PARP inhibitors alone and to chemotherapy. Heterogeneity was assessed using Higgins and Thompson's I2 statistic where applicable. Results: Seven RCTs involving 2397 patients were included. Combination therapy did not show a statistically significant improvement in PFS compared to PARP inhibitor monotherapy in the general population (HR 0.63, CI 0.37-1.06), or in BRCA-mutated (HR 0.70, CI 0.30-1.63) and BRCA wild-type subgroups (HR 0.39, CI 0.14-1.07). When compared to chemotherapy, combination therapy produced no significant PFS benefit in recurrent ovarian cancer (HR 0.83, CI 0.42-1.63) in the total population. Safety analysis revealed that hypertension and diarrhea were significantly more frequent in combination therapy compared with PARP inhibitors alone (RR 6.80, CI 2.87-16.06 and RR 10.04, CI 2.25-44.75) or chemotherapy alone (RR 13.80, CI 3.43-55.57 and RR 6.57, CI 2.84-15.24). Conclusions: The combination of PARP inhibitors and AAAs did not demonstrate a statistically significant benefit in PFS compared to PARP inhibitors or chemotherapy alone in recurrent ovarian cancer. While the combination therapy was generally well tolerated, hypertension and diarrhea occurred significantly. These findings suggest that combination therapy may not provide a clear survival advantage in the recurrent setting. Further high-quality, biomarker-driven clinical trials are needed to refine patient selection, optimize toxicity management, and determine the potential role of combination therapy in ovarian cancer treatment.

Dataset Information

A comprehensive systematic review and network meta-analysis: the role of anti-angiogenic agents in advanced epithelial ovarian cancer.

Publications

A comprehensive systematic review and network meta-analysis: the role of anti-angiogenic agents in advanced epithelial ovarian cancer.

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