Bevacizumab or PARP-Inhibitors Maintenance Therapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis

Int J Mol Sci. 2020 May 27;21(11):3805. doi: 10.3390/ijms21113805.

Abstract

Introduction: Targeted agents such as bevacizumab (BEV) or poly (ADP-ribose) polymerase inhibitors (PARPi) which have been added as concomitant or maintenance therapies have been shown to improve progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer (PS rOC). In the absence of direct comparison, we performed a network meta-analysis considering BRCA genes status.

Methods: We searched PubMed, EMBASE, and MEDLINE for trials involving patients with PS rOC treated with BEV or PARPi. Different comparisons were performed for patients included in the PARPi trials, according to BRCA genes status as follows: all comers (AC) population, BRCA 1/2 mutated (BRCAm), and BRCA wild type patients (BRCAwt).

Results: In the overall population, PARPi prolonged PFS with respect to BEV (hazard ratio (HR) = 0.70, 95% CI 0.54-0.91). In the BRCA mutated carriers, the PFS improvement in favor of PARPi appeared to be higher (HR = 0.46, 95% CI 0.36-0.59) while in BRCAwt patients the superiority of PARPi over BEV failed to reach a statistically significance level (HR = 0.87, 95% CI 0.63-1.20); however, according to the SUCRA analysis, PARPi had the highest probability of being ranked as the most effective therapy (90% and 60%, for PARPi and BEV, respectively).

Conclusions: PARPi performed better as compared with BEV in terms of PFS for the treatment of PS rOC, especially in BRCAm patients who had not previously received PARPi.

Keywords: PARP-inhibitors; bevacizumab; platinum-sensitive ovarian cancer.

Publication types

  • Network Meta-Analysis

MeSH terms

  • Antineoplastic Agents, Immunological / therapeutic use*
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Bevacizumab / therapeutic use*
  • Carboplatin / therapeutic use
  • Drug Resistance, Neoplasm
  • Female
  • Heterozygote
  • Humans
  • Mutation
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use*

Substances

  • Antineoplastic Agents, Immunological
  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Bevacizumab
  • Carboplatin