PARP inhibitor era in ovarian cancer treatment: a systematic review and meta-analysis of randomized controlled trials

J Ovarian Res. 2024 Feb 26;17(1):53. doi: 10.1186/s13048-024-01362-y.

Abstract

Background: Ovarian cancer is the eighth leading cause of cancer-related death among women, characterized by late diagnosis and a high relapse rate. In randomized controlled trials, we aimed to evaluate the efficacy and safety of PARP inhibitors (PARPi) in treating advanced ovarian cancer.

Methods: This review was registered on PROSPERO (CRD42021283150), included all phase II and phase III randomized controlled trials (RCTs) assessing the effect of PARPi on ovarian cancer until the 13th of April, 2022. The main outcomes were progression- free survival (PFS), overall survival (OS), and adverse events (AEs). Pooled hazard ratios (HRs), and risk ratios (RRs) were calculated with 95% confidence intervals (95% CI). The random-effects model was applied in all analyses.

Results: In the meta-analysis, 16 eligible RCTs were included, with a total of 5,815 patients. In recurrent ovarian cancer, PARPi maintenance therapy showed a significant PFS benefit over placebo in the total population (HR 0.34, CI 0.29-0.40), BRCA mutant (HR 0.24, CI 0.18-0.31), germline BRCA mutant (HR 0.23, CI 0.18-0.30), and BRCA wild-type cases (HR 0.50, CI 0.39-0.65). PARPi monotherapy also improved PFS (HR 0.62, CI 0.51-0.76) compared with chemotherapy in BRCAm patients with recurrent ovarian cancer. The use of PARPi maintenance therapy resulted in an improvement in PFS over placebo in newly-diagnosed cancers in the overall population (HR 0.46, CI 0.30-0.71) and the BRCAm population (HR 0.36, CI 0.29-0.44). Although the risk of severe AEs was increased by PARPi therapy compared to placebo in most settings investigated, these side effects were controllable with dose modification, and treatment discontinuation was required in the minority of cases.

Conclusions: PARPis are an effective therapeutic option for newly-diagnosed and recurrent ovarian cancer. Despite a minor increase in the frequency of serious adverse effects, they are generally well tolerated.

Keywords: HRD; Homologous recombination repair; Niraparib; Olaparib; Rucaparib.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Carcinoma, Ovarian Epithelial / drug therapy
  • Female
  • Humans
  • Neoplasm Recurrence, Local / drug therapy
  • Ovarian Neoplasms* / chemically induced
  • Ovarian Neoplasms* / drug therapy
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Randomized Controlled Trials as Topic

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors
  • Antineoplastic Agents