Metastatic castration resistant prostate ca has a life expectancy of 2 yr to 4 yr after onset of castration resistance. 20-30% of mCRPC pts have HRR mutations.
SOC: AR receptor blockers ( abiraterone, darolutamide, Enza)+ ADT, triplet with chemo, docetaxel with ADT. 2L-Rad 223, SipT, PARP inhibitors for HRR m ( olaparib) or BRCA ( rucaparib), pembro MSI high, Lu 177 3rdline.
1. Front line CRPC- olaparib+ abiraterone only for BRCAm whereas talazoparib+ enza is for all HRRm in the front line.
2. Olaparib single agent later line for all HRRm; rucaparib single agent later line for BRCA m.
3. Talazoparib+ Enza approved for 1st line HRR m CRPC. OS HR in HRR m population 0.69
4. TALAPRO study SE: 36% required prbc. Other se: fatigue, nausea, anorexia, neutropenia. 0.4% AML/MDS
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