Incorporating Parp-inhibitors in Primary and Recurrent Ovarian Cancer: A Meta-analysis of 12 phase II/III randomized controlled trials

Cancer Treat Rev. 2020 Jul:87:102040. doi: 10.1016/j.ctrv.2020.102040. Epub 2020 May 26.

Abstract

Background: The second decade of 2000s is witnessing a new ovarian cancer (OC) paradigm shift thanks to the results recently obtained by a new class of targeted agents: the Poly(ADP-ribose)polymerase (PARP)-Inhibitors (PARPi). Aim of this meta-analysis is to analyze available results obtained with PARPi, administered alone or in combination with chemo- and/or target-therapies in terms of efficacy and safety for the treatment of recurrent and primary advanced OC.

Methods: On December 2019, all published phase II/III randomized clinical studies were systematically searched using the terms "[Parp-Inhibitor] AND [ovar*]". Twelve phase II/III randomized controlled trials were identified, with a total number of 5171 patients included.

Results: Results demonstrated that PARPi account for a significant improvement of PFS in both recurrent and primary OC setting, independently from their administration schedule and independently from patients' BRCA mutational status. Moreover, patients harboring a Homologous Recombination Deficiency (HRD) positive testing primary or recurrent OC progress significantly later after PARPi administration/association. Results also reported that PARPi increase the occurrence of severe (G3-G4) anemia. Furthermore, severe fatigue occurred more frequently among patients subjected to PARPi combined with chemotherapy and to PARPi plus Bevacizumab. Finally, a significant increase in severe high blood pressure occurrence was observed when PARPi was added to antiangiogenetics, compared to PARPi alone but a significant decrease in G3-G4 hypertension occurrence was found in PARPi plus bevacizumab users compared to Bevacizumab alone.

Conclusions: PARPi are a valid option for the treatment of both primary and relapsed OC patients, with a relative low incidence of severe side effects.

Keywords: Niraparib; Olaparib; Ovarian cancer; Parp-inhibitor; Rucaparib; Veliparib.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Female
  • Humans
  • Ovarian Neoplasms / drug therapy*
  • Poly(ADP-ribose) Polymerase Inhibitors / administration & dosage*
  • Randomized Controlled Trials as Topic

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors