DARolutamide ObservationaL (DAROL) study in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).
Authors: Yu Evan Y. , Pieczonka Christopher Michael , Armstrong Andrew J. , Suzuki Hiroyoshi , Bailen James L. , Murphy Declan G. , Lebret Thierry , Luz Murilo , Thiery-Vuillemin Antoine , Ortiz Jorge A. , Khan Javeed , Briganti Alberto 
Published: June 2022

e17029

Background: Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor inhibitor that significantly increased median metastasis-free survival by ̃2 years and improved overall survival with a 31% reduction in risk of death vs placebo in men with nmCRPC in ARAMIS (NCT02200614), with a favorable tolerability profile. DARO significantly improved survival in men with metastatic hormone-sensitive prostate cancer (mHSPC) in ARASENS. The ongoing DAROL trial (NCT04122976) is designed to support results from the phase 3 ARAMIS study and to provide insight into the safety and effectiveness of DARO and the management of nmCRPC in the real-world setting. We report results of the first prespecified interim analysis. Methods: DAROL is an international, single-arm, non-interventional study. Eligible patients (pts) are DARO naïve, ≥18 years of age, with confirmed nmCRPC, for whom the decision to treat with DARO was made before enrollment. Treatment dose and duration are per investigator’s routine practice. The primary endpoint is safety, including treatment-emergent adverse events (TEAEs). Prostate-specific antigen (PSA) response was an exploratory objective. Descriptive statistics are reported for the first prespecified interim analysis (cut-off: September 23, 2021) performed after ̃100 pts (from US, Canada, Japan) completed ≥6 months of treatment or discontinued treatment. Results: All 100 pts were evaluable for safety: median age 78.0 years; White/Black/Asian/other/not reported, 59%/11%/27%/1%/2%; North America/Asia Pacific, 79%/21%; baseline ECOG performance status 0–1/2–4/not reported, 72%/5%/23%; median (Q1–Q3) time from initial diagnosis to castration-resistant, 89.1 mo (39.1–130.6 mo); Gleason score at initial diagnosis ≤6/7/8–10, 15.8%/38.9%/45.3%; baseline PSA ≤10/ > 10 ng/mL, 75.3%/24.7%; PSA doubling time ≤6/ > 6 mo, 58.2%/41.8%. Median (Q1–Q3) duration of treatment was 11.3 mo (8.4–14.4 mo); median (Q1–Q3) follow-up time was 12.3 mo (9.6–15.6 mo). Median starting dose and daily treatment dose was 1200 mg daily. 28% of pts had TEAEs of any grade, with 3% grade 3; no grade ≥4. 2% of pts had serious adverse events (AEs). Incidence rates of AEs were generally low, consistent with the safety profile observed in ARAMIS, and those that occurred in ≥2% of pts were fatigue (5%), diarrhea (5%), asthenia (2%), muscle weakness (2%), anemia (2%), and rash (including rash pruritic, 2%). TEAEs led to permanent study drug discontinuation in 7% of pts. Of 93 pts evaluable for efficacy, the percentage with a PSA response of ≥30%, ≥50%, and ≥90% at any time during follow-up was 81.7%, 77.4% and 52.7%, respectively. Conclusions: At the first interim analysis of the DAROL observational study in the real-world setting, the safety and tolerability of DARO was consistent with the favorable tolerability profile observed in the randomized ARAMIS trial. Clinical trial information: NCT04122976.