Real-world discontinuation rates among patients with metastatic castration-sensitive prostate cancer who initiated novel androgen receptor inhibitors: A US claims analysis.

568 Background: Novel androgen receptor pathway inhibitors (ARPI) apalutamide (Apa), darolutamide (Daro), and enzalutamide (Enza) have been shown to be efficacious in clinical trials and are increasingly being utilized as first line therapies in metastatic castration-sensitive prostate cancer (mCSPC). There is limited evidence available on ARPI utilization and duration of therapy (DOT), in the real-world setting. Methods: This retrospective cohort analysis used the IQVIA Real-World Data Adjudicated Claims, a US claims database. Patients diagnosed with mCSPC who initiated ARPI treatment as first treatment between January 1, 2020 and January 31, 2025 were included. Patients with concomitant docetaxel use were excluded. Discontinuation was defined as a gap of ≥60 days from the end of days supply. Inverse probability treatment weighting (IPTW) was used to minimize potential baseline confounders. Cox proportional hazards models were used to compare the time to discontinuation between patients initiated on Apa, Daro, and Enza. Results: 10,351 patients with mCSPC initiated an ARPI (2,372 Apa; 901 Daro; 7,078 Enza). Patient characteristics were well balanced after IPTW (mean age: 69 years, 72% of patients were ≥65 years, and 58% had Medicare coverage). Patients receiving Daro had the lowest overall rate of discontinuation (52.3%) vs the Apa (61.4%) and Enza (64.8%) cohorts ( P <0.0001). This trend was consistent at 3, 6, and 12 months (Table 1). The median duration of treatment was also longest in the Daro cohort (444 days [IQR: 183-1,059]) vs the Apa (366 days [IQR: 152-854]) and Enza (349 days [IQR: 150-781]) cohorts. After weighting, patients in the Daro cohort had significantly lower risk of discontinuation compared to Apa (HR: 0.88 [95% CI: 0.82-0.95]) and Enza (HR: 0.89 [95% CI: 0.82-0.96]) cohorts. Conclusions: Real-world discontinuation is considered a treatment-based proxy of disease progression in oncology. In this large cohort, patients with mCSPC treated with Daro had significantly lower risk of discontinuation and longer treatment durations vs those receiving Apa or Enza. Further research is warranted to confirm these benefits and explore the underlying reasons for reduced discontinuation and prolonged treatment duration. Discontinuation rate by treatment cohort in IPTW weighted cohort. DarolutamideN=901 ApalutamideN=934 EnzalutamideN=948 P -value Median follow-up time (days) 461 525 495 - Index drug discontinuation, n (%) 471 (52.3) 574 (61.4) 615 (64.8) <0.0001 Discontinuation within 3 months, n (%) 130 (14.4) 169 (18.1) 148 (15.6) 0.086 Discontinuation within 6 months, n (%) 226 (25.1) 287 (30.7) 279 (29.5) 0.0207 Discontinuation within 12 months, n (%) 363 (40.3) 447 (47.9) 467 (49.2) 0.0002