Background: In ARAMIS (NCT02200614), darolutamide (DARO) significantly improved metastasis-free survival (MFS) by ~2 years (HR 0.41, 95% CI 0.34–0.50) and reduced the risk of death by 31% (HR 0.69, 95% CI 0.53–0.88) compared with placebo in men with nonmetastatic castration-resistant prostate cancer (nmCRPC), with a favorable tolerability profile. The ongoing DAROL study (NCT04122976) aims to understand the real-world safety and effectiveness of DARO in patients (pts) with nmCRPC. We report results from the pre-planned second interim analysis (IA). Methods: DAROL is a global, open-label, single-arm, non-interventional study in pts aged ≥18 years with confirmed nmCRPC for whom the decision to be treated with DARO is decided pre-enrollment. The primary endpoint is safety, including incidence, severity, and frequency of treatment-emergent adverse events (TEAEs). Secondary endpoints are patient demographics and disease characteristics, treatment duration, MFS, overall survival (OS), time to prostate-specific antigen (PSA) progression, and PSA response. Primary and secondary endpoints are reported after 300 pts completed ≥6 mo of treatment. All treated pts were assessed for safety while efficacy was evaluated in pts who did not violate any eligibility criteria and had ≥1 post-baseline assessment (cut-off October 11, 2022). Results: Of the 300 treated pts, the percentage enrolled in North America/Europe/Asia Pacific/Latin America was 45%/30%/25%/ < 1%, respectively. Median age was 80 years; 51% had a reported Gleason score > 7; 92% had a reported ECOG performance status of 0/1. Median baseline (BL) PSA was 3.9 ng/mL (range 0–248.0), with 21% of pts reporting PSA < 2 ng/mL. Median BL PSA doubling time (PSADT) was 5.3 mo (range 0–36.2), with 42% of pts reporting PSADT > 6 mo. At the data cut-off, median follow-up time was 14.8 mo (interquartile range [IQR] 10.9–19.3) and median treatment duration was 13.4 mo (IQR 9.3–17.8). The incidences of TEAEs and DARO-related TEAEs were generally low (Table), consistent with the safety profile of DARO reported in ARAMIS. Fatigue occurred in ≥5% of pts. For the 263 pts eligible for efficacy analysis, median time to PSA progression was 17.6 mo (95% CI 13.2–19.0); MFS/OS data remain immature. PSA declines from baseline of ≥30%, ≥50%, and ≥90% at any time were observed in 80%, 76%, and 54% of pts, respectively. Conclusions: In the DAROL second IA, under real-world conditions, DARO continued to show a favorable safety profile, consistent with the clinical profile of ARAMIS, with no new safety signals. Clinical trial information: NCT04122976.

*TEAEs observed in ≥2% of pts ^†N = 300 NR, not reported.