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 Jan 18;10600280221149136. doi: 10.1177/10600280221149136. Online ahead of print.


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.