Discontinuation rates among patients with metastatic castration-sensitive prostate cancer (mCSPC) initiating novel androgen receptor inhibitors in oncology and non-oncology settings.

Abstract

105 Background: Novel androgen receptor pathway inhibitors (ARPI) apalutamide (Apa), darolutamide (Daro), and enzalutamide (Enza) have demonstrated improved outcomes in mCSPC clinical trials; however, real-world evidence describing treatment patterns is limited. This study assessed the real-world duration of therapy (DOT) and time to discontinuation of ARPIs as doublet therapy across oncology and non-oncology settings. Methods: This retrospective cohort analysis used the IQVIA Real-World Data (Adjudicated US Claims data). Adult men with mCSPC who initiated ARPI treatment as initial treatment between January 1, 2020 and January 31, 2025 were included. Patients receiving concomitant docetaxel were excluded. Discontinuation was defined as a ≥60-day gap following the end of supply. Patients were stratified by care setting at treatment initiation as oncology vs. non-oncology (including urology and others). Inverse probability treatment weighting (IPTW) was used to minimize potential baseline confounders. Cox proportional hazards models compared time to discontinuation between ARPIs. Results: Among 10,239 mCSPC patients initiating ARPI (Apa: n=2,340; Daro: n=889; Enza: n=7,010), 1,301 Apa, 625 Daro, and 4,708 Enza started in oncology settings; the remainder in non-oncology settings. After IPTW patient characteristics were well balanced. In oncology settings, Daro had the lowest discontinuation rate (53.0%) vs. Apa (62.8%) and Enza (66.2%) (p<0.0001). Median DOT was also longest in the Daro cohort (422 days [IQR: 180-1997]) vs Apa (369 days [IQR: 150-833]) and Enza (362 days [IQR: 150-811]). Daro had significantly lower risk of discontinuation compared to Apa (HR 0.87, 95% CI 0.8- 0.96) and Enza (HR 0.86, 95% CI 0.78- 0.94). In non-oncology settings, after IPTW (Apa: n=320; Daro: n=240; Enza: n=285), discontinuation rates were 50.7%, 58.8%, and 61.7%, respectively (p=0.024). Risk of discontinuation was not significantly different (Daro vs Apa: HR 0.91, 95% CI 0.8-1.02 and Daro vs Enza: HR 0.95, 95% CI 0.84-1.08). Conclusions: mCSPC patients treated with Daro in the oncology setting had significantly lower risk of discontinuation and longer treatment durations vs those receiving Apa or Enza. In non-oncology settings, Daro showed a numerically lower discontinuation rate, though time-to-discontinuation was not statistically significant, likely due to smaller sample sizes. Discontinuation rate by IPTW treatment cohort in the oncology setting. Daron=625 Apan=614 Enzan=653 p -value Median follow-up time (days) 479 550 490 Index drug discontinuation, n (%) 331 (53.0) 386 (62.8) 432 (66.2) <0.0001 3 month discontinuation, n (%) 91 (14.6) 114 (18.5) 105 (16.0) 0.163 6 month discontinuation, n (%) 158 (25.3) 191 (31.1) 196 (30.1) 0.0538 12 month discontinuation, n (%) 248 (39.7) 300 (48.8) 330 (50.6) 0.0002