Treatment of Metastatic Castration-Resistant Prostate Cancer with PARP Inhibitors

Established PARP Inhibitor Combinations

The National Comprehensive Cancer Network (NCCN) recommends Olaparib + Abiraterone for BRCA1/2 mutation-positive metastatic castration-resistant prostate cancer (mCRPC) patients, with a Category 1 recommendation for treatment-naïve patients without prior docetaxel or novel hormone therapy 1, 2
The NCCN recommends Talazoparib + Enzalutamide for HRR gene mutations (BRCA1, BRCA2, ATM, ATR, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C) in treatment-naïve mCRPC patients, with a Category 1 recommendation 3, 4, 5
The NCCN recommends Niraparib + Abiraterone for BRCA1/2 mutation-positive mCRPC patients, with a Category 1 recommendation for treatment-naïve patients 6, 7, 8

Androgen receptor inhibitors downregulate DNA repair genes, creating synthetic lethality when combined with PARP inhibition, which improves radiographic progression-free survival even in patients without HRR mutations 1, 2, 9

Hematologic toxicities, including anemia (21-33% grade ≥3), thrombocytopenia, and neutropenia, are common with PARP inhibitors and require careful monitoring 3, 5
Dose interruptions are required in 75% of patients receiving talazoparib combinations, and dose reductions are needed in 56% of patients due to adverse events 3, 4, 5