Evaluation of the Efficacy and Safety of PARP Inhibitors in Advanced-Stage Epithelial Ovarian Cancer

Abstract

Purpose: PARP inhibitors are a novel targeted anti-cancer drug and a large number of clinical studies on PARP inhibitors have been accomplished. This updated meta-analysis was conducted to evaluate the efficacy and safety of PARP inhibitors in advanced-stage epithelial ovarian cancer. Methods: Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus were searched to identify the eligible trials up to April 2020. ClinicalTrials.gov was also screened for additional unpublished trials. Data extraction and risk of bias assessment were performed by two independent investigators, respectively. The hazard ratios (HRs) and its 95% confidence intervals (CI) for time-to-event data of progression-free survival (PFS) and overall survival (OS), and the risk ratios (RRs) with 95% CI for dichotomous data of overall response rate (ORR) and occurrence of adverse events (AEs) were calculated by Review Manager 5.3 and Stata 12.0 software. Results: A total of 12 trials with 5,347 patients were included in this meta-analysis. Compared with the control group, PARP inhibitors significantly improved PFS (HR, 0.51; 95% CI, 0.40-0.65; P < 0.00001) and ORR (RR, 1.26; 95% CI, 1.11-1.43; P = 0.0003). Specifically, PFS was improved regardless of BRCA genes mutations and homologous-recombination status. However, no difference was observed in OS between the PARP inhibitors group and the control group (95% CI, 0.73-1.01; P = 0.06). PARP inhibitors were associated with a statistically significant higher risk of hematologic events and different PARP inhibitors had different toxicities profiles. Conclusion: PARP inhibitors are an effective and well-tolerated treatment for patients with advanced-stage epithelial ovarian cancer.

Keywords: PARP inhibitors; epithelial ovarian cancer; maintenance treatment; meta-analysis; niraparib; olaparib; rucaparib; veliparib.

Figure 1

Flow Diagram of Trials Selection. *Finally, 13 articles of 11 trials and 1 additional unpublished trial (SOLO3) with completed results were included. Study 19 had three different articles which were published by Ledermann et al. (14, 21, 22). Analysis of outcomes according to BRCA status was published in 2014 and the updated overall survival analysis was published in 2016 at 77% data maturity.

Figure 2

Risk of bias graph.

Figure 3

(A) Forest plot of hazard ratios (HRs) comparing progression-free survival (PFS) of patients treated with PARP inhibitors vs. placebo or chemotherapy; the HRs plot for PFS of subgroup analysis by genes mutational status (B) and treatment lines (C).

Figure 4

(A) Forest plot of risk ratios (RRs) comparing overall response rate (ORR) of patients treated with PARP inhibitors vs. placebo or chemotherapy; (B) Forest plot of hazard ratios (HRs) comparing overall survival (OS) of patients treated with PARP inhibitors vs. placebo or chemotherapy.

Figure 5

Forest plot of risk ratios (RRs) comparing adverse events (AEs) of any grade or grade 3 or higher in patients treated with PARP inhibitors vs. placebo or chemotherapy.