Real-World Efficacy and Safety of PARP Inhibitors in Recurrent Ovarian Cancer Patients With Somatic BRCA and Other Homologous Recombination Gene Mutations

Ann Pharmacother. 2023 Oct;57(10):1162-1171. doi: 10.1177/10600280221149136. Epub 2023 Jan 18.

Abstract

Background: Real-world data regarding the use of poly (ADP-ribose) polymerase (PARP) inhibitors in recurrent ovarian cancer patients with non-BRCA homologous recombination (HR) mutations or somatic BRCA mutations are lacking.

Objective: The purpose of our study is to evaluate the response rate, duration of treatment, time to progression (TTP), and toxicities of olaparib, niraparib, and rucaparib in somatic BRCAm and non-BRCA HR-mutated patients.

Methods: This was a retrospective study using the electronic medical record to identify patients across our health system who were initiated on a PARP inhibitor for ovarian cancer between December 2014 and December 2019. Patients were screened for the presence of a somatic BRCA1/2 mutation or a mutation in non-BRCA HR genes. Data were collected via chart review.

Results: For the efficacy analysis, 8 patients had somatic BRCA mutations and 12 patients had HR mutations. The overall response rate (ORR) was 50% for BRCA-mutated (BRCAm) patients and 9.1% for non-BRCA HR-mutated (non-BRCA HRm) patients. 72.7% of patients with non-BRCA HR mutations had stable disease. The duration of therapy ranged from 2 to 66 months. The median TTP was 9.5 months. Overall, 66.7% of patients in the entire cohort started on a reduced dose of PARP inhibitor. Dose reductions due to AEs were observed in 52.4% of patients, while AEs requiring treatment interruption occurred in 61.9%.

Conclusion and relevance: We found that PARP inhibitors provided stable disease in a high proportion of recurrent ovarian cancer patients who had pathogenic HR mutations, with toxicities comparable to major trials. Patients with non-BRCA HR and somatic BRCA mutations could benefit from PARP inhibitors.

Keywords: homologous recombination deficiency; niraparib; olaparib; ovarian cancer; rucaparib; somatic BRCA mutations.

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Carcinoma, Ovarian Epithelial / drug therapy
  • Carcinoma, Ovarian Epithelial / genetics
  • Female
  • Homologous Recombination
  • Humans
  • Mutation
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / pathology
  • Poly(ADP-ribose) Polymerase Inhibitors / adverse effects
  • Retrospective Studies

Substances

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