Treatment outcomes for patients (Pts) with metastatic castration resistant prostate cancer (mCRPC) pts and DNA damage repair gene mutations.

5069Background: DDRm occur in 15-30% of pts with mCRPC. While BRCA2 germline mutations are linked to aggressive local disease, outcomes in pts with mCRPC and DDRm continue to be characterized. Methods: Leukocyte DNA from 631 consecutive mCRPC pts were screened for germline ATM, BRCA1/2, CDK12, and PALB2 truncating mutations using targeted sequencing. 312/631 were assessed for somatic DDRm (sDDRm) and homozygous deletions in the same genes, using matched plasma cell-free DNA. Additional pts with gDDRm were identified through our hereditary cancer program (HCP). We examined time from androgen deprivation therapy (ADT) initiation (± docetaxel) to CRPC; time to PSA progression (TTPP), PSA response (50% decline from baseline), and objective response rate (ORR) on 1st-line AR-targeted therapy, docetaxel, PARP inhibitor, platinum-based chemotherapy, and radium-223 for mCRPC; and overall survival (OS). Outcomes in pts with DDRm and pts with DDR wild-type (WT) status (with available clinical data, n = 113) were co...