Comparative outcomes of abiraterone and androgen receptor inhibitors (ARPIs) in metastatic castration-sensitive prostate cancer (mCSPC): A real-world analysis from the TriNetX database.

e17119 Background: Abiraterone and ARPIs, including enzalutamide and apalutamide, in combination with androgen deprivation therapy (ADT), are standard treatments for metastatic castration - sensitive prostate cancer (mCSPC). However, direct comparisons of their efficacy and safety are limited due to the absence of head-to-head trials. This study leverages real- world data to compare treatment outcomes, including Prostate-Specific Antigen (PSA) response and progression risk to metastatic castration-resistant prostate cancer (mCRPC). Methods: Using the TriNetX Research Network (2010–2024), we identified mCSPC patients treated with abiraterone (n=681), enzalutamide (n=252), or apalutamide (n=121) in combination with ADT (91–98% receiving a GnRH analog, primarily leuprolide). Outcomes included the risk of hormone resistance (ICD-10 Z19.2) and a combined endpoint of hormone resistance or docetaxel use. We also assessed the percentage of patients with sustained PSA response (PSA ≤ 4 ng/mL) at 12 months. Baseline PSA levels were recorded for each cohort. Kaplan-Meier analysis and measures of association risk assessment were used to evaluate risk and time to hormone resistance, combined endpoint and PSA trends. Results: The risk of hormone-resistant malignancy was highest with enzalutamide (52.51%, median 278 days), followed by abiraterone (44.02%, median 707 days), and lowest with apalutamide (23.93%, median time not reached; follow-up to 1,895 days). For the combined outcome, enzalutamide had the highest risk (48.21%, median 493 days), followed by abiraterone (44.51%, median 666 days), and apalutamide (24.79%, median time not reached). Baseline mean PSA levels were 89.4 for enzalutamide, 63.6 for apalutamide, and 49.9 for abiraterone. Apalutamide demonstrated the highest percentage of sustained PSA response (41.07%), followed by abiraterone (37.5%) and enzalutamide (21.8%). Conclusions: This real-world analysis highlights significant differences in treatment outcomes for mCSPC. Enzalutamide was associated with the highest risk of progression, while apalutamide demonstrated the most favorable outcomes, including higher sustained PSA reductions and lower progression risk. Baseline PSA differences may partially explain these findings. Prospective trials with head-to-head comparisons are needed to validate these results and guide personalized treatment strategies in mCSPC.