Real-world use of novel hormonal therapies in European and North American patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC).

86 Background: Androgen receptor pathway inhibitors (ARPIs) are essential for mHSPC treatment; however, global use may vary. Insights into real-world use of ARPIs by region are needed to understand differences in global treatment practices. Methods: This observational cohort study included newly diagnosed pts with mHSPC enrolled in the IRONMAN registry between June 2017 and March 2025 in Europe (EU) (Ireland, Norway, Spain, Sweden, Switzerland, UK) and North America (NA) (Canada, USA), with ≥3 months follow-up. Outcomes were the proportion of pts with mHSPC receiving initial ARPI (index date), Kaplan-Meier estimated ARPI discontinuation rate (DR), and physician-reported reasons for discontinuation. Results: 2545 pts with mHSPC were included (EU n=1129; NA n=1416). Median age was 71 years (range 43–94) in EU and 70 years (range 32–95) in NA. The majority of pts were White (EU: 74%; NA: 65%) and non-Hispanic (EU: 70%; NA: 79%). Median PSA levels at enrollment were 3.6 ng/mL in EU and 7.6 ng/mL in NA. Most pts had ECOG PS 0 (EU: 67%; NA: 56%). Median time from mHSPC diagnosis to index date was 2.2 months in EU and 1.9 in NA. Median follow-up was 24.0 months in both cohorts. The most common metastatic site was bone ± nodal (EU: 72%; NA: 66%), followed by visceral ± nodal or bone (EU:15%; NA: 22%), and nodal only (EU: 13%; NA: 12%). Initial chemotherapy use (including docetaxel DOC ± ADT and DOC + ADT + ARPI) was 19% of pts in EU and 11% in NA, while 67% of pts in each region used initial ARPI (Table). In EU, initial ARPI use increased from 0 pts in 2017 and 2018, to 20 (19%) in 2019, 97 (49%) in 2020, 152 (64%) in 2021, 170 (79%) in 2022, 205 (90%) in 2023, and 94 (84%) in 2024. Initial ARPI use was higher in NA from 2017 to 2021: 26 pts (79%) in 2017, 129 (58%) in 2018, 162 (59%) in 2019, 77 (71%) in 2020, 129 (71%) in 2021, 127 (73%) in 2022, 163 (71%) in 2023, and 113 (77%) in 2024. ARPI DR at 24 months was higher in NA (42%) vs EU (31%), with a similar distribution of discontinuation reasons. A small number of pts switched therapies, including to other ARPIs. Conclusions: In this real-world study, ARPI use increased over time, although EU lagged NA; initial chemotherapy use was higher in EU. A substantial proportion of patients discontinued ARPI within 24 months, particularly in NA, mainly due to progressive disease or adverse events. Further comparative studies are needed to guide optimal treatment decisions across regions, and whether to explore harmonization across regions. Clinical trial information: NCT03151629 . EU( n = 1129) NA ( n = 1416) Total ( N = 2545) Received initial ARPI, n (%) 756 (67) 949 (67) 1705 (67) Received initial chemotherapy, n (%) 209 (19) 158 (11) 367 (14) DR 24 months, n (%) 231 (31) 402 (42) 633 (37) Discontinuation reason, n (%)Progressive diseaseAdverse eventDeathPhysician decisionOther/unknown/lost to follow-up 88 (12)37 (5)38 (5)31 (4)37 (5) 109 (12)64 (7)48 (5)52 (6)129 (14) 197 (12)101 (6)86 (5)83 (5)166 (10)