Use of poly (adp-ribose) polymerase inhibitors (PARPi) in metastatic castration resistant prostate cancer (mCRPC) patients stratified by homologous recombination repair mutations.

Abstract

e17053 Background: Approval of the PARPi in May 2020 caused a paradigm shift in the treatment of mCRPC patients with homologous recombination repair (HRR) mutations. Gaps remain in the optimal prescribing of PARPi in eligible patients, with negative consequences on clinical outcomes. The goal of this study was to look at PARPi prescribing practices in patients with HRR mutations overall and by sub-mutation. Methods: The Integra Connect PQ-deidentified real-world database was used, comprising over 1 million cancer patients across 275 sites of care, of which 80% were community practices and 20% academic settings. We performed medical chart reviews and identified 261 patients with HRRm mCRPC that received therapy between 5/1/2020 to 1/24/2023. We segmented patients into BRCA-positive with or without other HRR mutations, ATM positive without BRCA mutations and with or without other HRR mutations, and other HRR mutations without BRCA or ATM mutations. We compared utilization of PARPi in HRRm patients by sub-group. Descriptive statistics were used to assess proportions of utilization of PARPi treatment among HRRm patients. Proportions were compared using the two-proportion z-test. Results: Among HRRm mCRPC patients with prior next-generation hormonal agent (NHA) treatment, the use of PARPi is 61% (158 of 261). Among HRRm mCRPC patients who received PARPi after prior NHA treatment, 76% (78 of 103) were in the BRCA positive group, 62% (48 of 78) in the ATM positive group and 40% (32 of 80) in the other HRR mutations positive group. Patients in the BRCA positive group were more likely to receive a PARPi than those in either the ATM or other HRR mutations group (p < 0.01). Patients harboring ATM mutations were more likely to receive a PARPi than patients with non-BRCA HRR mutations (p < 0.01). Conclusions: This real-world study shows an opportunity to increase rates of PARPi treatment in patients with HRRm mCRPC across all HRR gene mutations. mCRPC patients with BRCA and ATM mutations were more likely to receive PARPi than those with other HRR mutations.