GU Cancers 2021 | PARP inhibitors: activity in BRCA1 versus BRCA2 altered mCRPC

Emmanuel Antonarakis, MBBCh, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, discusses the differential impact of PARP inhibitors in BRCA1- versus BRCA2-altered metastatic castration-resistant prostate cancer (mCRPC). Two PARP inhibitors, olaparib and rucaparib, have recently received FDA approval for mCRPC patients with BRCA1/2 mutations. A retrospective study analyzed data from 123 patients with mCRPC patients treated with PARP inhibitors. PSA50 responses (over 50% decline in prostate-specific antigen level) were observed in 38% of BRCA1 versus 65% of BRCA2 patients. Median progression-free survival (PFS) was 3 months for BRCA1 patients and 8 months for BRCA2 patients. Overall, the study found that PARP inhibitor activity was reduced in patients with mCRPC and mutant BRCA1 compared to activity in patients with mutant BRCA2. This interview took place during the 2021 Genitourinary Cancers Symposium.