When would you use PARP inhibitors in patients with refractory metastatic castrate resistant prostate cancer with somatic non-BRCA HRD mutations?

This is a very relevant question as clearly there is major heterogeneity in the outcomes with both olaparib and rucaparib in men with mCRPC based on their underlying germline or somatic tumor genomics. In addition, prior therapy and available alternatives including clinical trials with more or less ...

The majority of CHEK2-altered mCRPC patients will not benefit significantly from PARP inhibitor therapy, although a subset will. Recent data suggest that prostate cancers from germline CHEK2-altered patients have much lower homologous recombination deficiency (HRD) scores than gBRCA2- and gATM-alter...

I use PARP inhibitors for patients with mCRPC and a mutation in BRCA2, BRCA1, PALB2, RAD51 homologs (all closely involved in homologous recombination repair), and if possible FANCA. Response rates are highest for BRCA2 and PALB2 (the latter based on more limited data as it is less frequently mutated...