The effect of PARP inhibitors in homologous recombination proficient ovarian cancer: meta-analysis

Abstract

BRCA1/2 mutations and homologous recombination deficiency (HRD) predispose to increased sensitivity to poly(ADP-ribose)polymerase (PARP) inhibitor treatment. Our aim was to evaluate the PARP inhibitors effect on progression free survival (PFS) in a subpopulation with homologous recombination proficient status (HRD-BRCA-). A systematic literature search was performed for all studies reporting on the effect of PARP inhibitors regarding PFS in the HRD-BRCA- subpopulation, in patients with epithelial ovarian, tubal or primary peritoneal cancers (EOC). Five studies were included, enrolling a population of 3413 patients, with 1070 of them being HRD-BRCA-. PARP inhibitors were effective in the treatment of EOC, regardless of HRD and BRCA status or line of therapy. The estimated pooled effect hazard ratio (HR), assessing PFS for PARP inhibitors compared with control, was 0.76 (95% CI: 0.65–0.88, I² = 46%) in the HRD-BRCA- subpopulation. Comparing both subpopulations with HRD positive status (HRD+ BRCA+, HRD+ BRCA-) versus the HRD-BRCA-subpopulation, we have found statistically significant differences in the effect on PFS (P < 0.05 for every interaction test) favouring HRD positive subpopulations (HRD+ BRCA+, HRD+ BRCA-). In the HRD-BRCA- subpopulation of patients, PARP inhibitors used as the second- or later-line of therapy showed more pronounced effect then when given as first line treatment (P = 0.04). Treatment of EOC with PARP inhibitors showed a significant effect regarding PFS in the HRD-BRCA- subpopulation, although a much higher benefit was evident for patients with HRD+ status (HRD+ BRCA+ and HRD+ BRCA-). In the HRD- subpopulation second line PARP inhibitor treatment showed greater benefit compared to first line PARP inhibitor treatment.

Keywords:

• PARP inhibitors
• homologous recombination deficiency
• BRCA genes
• ovarian cancer
• niraparib
• rucaparib
• veliparib
• olaparib

Acknowledgment

We want to thank Tanja Miketic for proofreading this article.

Disclosure of interest

The authors declare no conflict of interest. All authors read and approved the final manuscript.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Data availability statement

Data available on request from the authors.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.