Real-world treatment patterns and survival in men with metastatic castration-resistant prostate cancer (mCRPC) who previously progressed from metastatic hormone-sensitive prostate cancer (mHSPC) between 2020 to 2023 in the United States.

99 Background: While androgen deprivation therapy (ADT) is a backbone for managing mHSPC, therapies initially approved for mCRPC, such as androgen receptor pathways inhibitors like abiraterone (ABI) and non-ABI ARPIs ( enzalutamide, apalutamide, darolutamide), and/or docetaxel, are now guideline-recommended for use in mHSPC. Evidence on how this shift in mHSPC management affects current mCRPC treatment patterns and survival is lacking. Methods: A retrospective cohort of men treated for mCRPC between 2020-2023 was identified in the ConcertAI NLP360 oncology electronic medical records (EMR) database in the United States. Men with mCRPC were identified based on their first record for castration resistance after an earlier diagnosis of mHSPC. Men were required to have continuous EMR activity ≥12 months pre-mCRPC (baseline) and ≥6 months post-mCRPC. Line of therapy was identified as ABI, non-ABI ARPI, taxane-based chemotherapy, poly (ADP-ribose) polymerase inhibitors (PARPIs), immunotherapy (pembrolizumab, sipuleucel-T), radiopharmaceuticals (Ra-223, 177 Lu-PSMA-RLT), alone or in combination. Results: The cohort comprised 609 men with mCRPC who had progressed from mHSPC. Median age was 72 years (interquartile range: 66-79). Nearly 85% had ECOG 0-1, 79% had bone metastases, and 42% received bone-health agents during baseline. Most men had received ADT alone for mHSPC (53%), followed by ADT+ABI (19%), ADT+non-ABI ARPI (18%), and ADT+Docetaxel (10%). Overall, the most common first line treatment (1L Tx) for mCRPC was ARPI (62%; enzalutamide [28%] and ABI [25%]) and chemotherapy (22%). This trend was consistent in men with prior ADT for mHSPC. Among those who had received ADT+ARPI for mHSPC, sequentially ARPI as 1L Tx was common (most common on ADT+ABI and 2 nd most common among ADT+non-ABI ARPI). 1L chemotherapy use was more common among men with ADT+ARPI/DOC for mHSPC, compared to ADT alone (see Table 1), though was still less than 50% in the ADT+non-ABI ARPI group. Median real-world overall survival from 1L Tx was 21 months (95% confidence interval: 18, 25). Conclusions: With more than half of patients having received ADT alone in mHSPC, use of ARPIs was the most common 1L Tx option in mCRPC. Back-to-back use of ARPI upon progression to mCRPC was common. These findings highlight the need to explore alternative treatment option in mCRPC beyond ARPIs to improve survival in men with mCRPC. 1L mCRPC treatment patterns by prior mHSPC therapy. 1L Therapy Overall Prior mHSPC Therapy, n ADT ADT+ABI ADT+non-ABI ARPI ADT+DOC Cohort Size 609 320 (53%) 118 (19%) 109 (18%) 62 (10%) Non-ABI APRI 226 (37%) 138 59 7 22 ABI 153 (25%) 103 - 37 13 Chemotherapy 136 (22%) 38 38 45 15 Immunotherapy 28 (5%) 15 3 6 4 Radiopharmaceuticals 19 (3%) 7 3 6 3 PARPi 13 (2%) 4 4 3 2 Combination Therapy 34 (6%) 15 11 5 3