Background: Novel androgen receptor inhibitors (ARIs) are recommended for pts with nmCRPC. Daro has a distinct structure with low blood-brain barrier penetration which may lead to a lower risk of central nervous system-related adverse events (AEs) and minimal risk of AEs commonly associated with ARIs. DEAR is the first study comparing RW utilization, outcomes, and AEs between daro and enza/apa in nmCRPC pts. Methods: This retrospective chart review cohort study uses electronic medical records from the PPS network of US urology practices. Eligible pts had nmCRPC, no prior novel hormonal therapy, and initiated first ARI treatment (index date) between 8/2019-3/2022. We describe the % of pts who discontinued initial ARI treatment (DISC), % who progressed to metastasis (PROG), and % with AEs. A comparative analysis was performed between daro and enza/apa using Cox proportional hazards models for time to DISC/time to PROG, adjusting for observed baseline (BL) factors. Results: 870 pts were included (daro/enza/apa, n=362/382/126). Median age (80/79/80 y), median BL prostate-specific antigen (PSA) doubling time (6.8/6.4/7.4 mo), other BL characteristics, and median follow-up (22.2/22.7/23.3 mo) were similar for daro/enza/apa. A lower % of pts had a DISC event on daro vs enza/apa (30.4 vs 40.8/46.0) or a PROG event (17.7 vs 28.3/27.8) during the study period. Multivariate analyses adjusting for BL factors showed that pts on daro had a lower risk of DISC and PROG over time vs enza/apa. A lower % of pts on daro had AEs vs enza/apa (24.9 vs 29.3/30.2). Conclusions: Overall, a lower % of pts discontinued initial ARI treatment, progressed to metastasis, or had AEs on daro vs enza/apa. In analyses adjusting for observed BL factors, pts on daro had considerably lower risk of DISC and PROG vs enza/apa. This study confirms daro’s strong efficacy and favorable tolerability profile in a RW setting. The longer treatment duration seen with daro may be associated with a lower risk of progression to mCRPC vs enza/apa.

^aAdjusted for age at index, race, insurance coverage, index yr, BL PSA, BL PSA doubling time, time from CRPC to index date, and Gleason score. ^bDISC was defined as occurrence of any of the following: initial ARI treatment stop/switch to another ARI/death. ^cPROG was defined as evidence of bone, visceral/soft tissue, or distant nodal metastases, such as secondary neoplasm diagnosis codes or codes associated with a PC-related claim, manual data entry in patient charts, and/or initiation of mCRPC treatment (abiraterone, sipuleucel-T, docetaxel, cabazitaxel, mitoxantrone, or radium-223).