(UroToday.com) The 2025 ESMO annual meeting featured a prostate cancer session and a presentation by Dr. Murilo de Almeida Luz discussing results from a prespecified interim analysis of the DAROL prospective observational study assessing real-world experience with darolutamide in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). Darolutamide is a highly potent androgen receptor inhibitor, structurally distinct by design, with low blood-brain barrier penetration, and limited potential for clinically relevant drug-drug interactions. Darolutamide is approved for nmCRPC based on significant metastasis free survival,1 and overall survival2 benefits versus placebo and favorable safety in the phase 3 ARAMIS study. In ARAMIS, darolutamide + ADT significantly improved metastasis free survival by ~2 years and significantly reduced the risk of death by 31% versus placebo + ADT; darolutamide demonstrated a favorable safety and tolerability profile similar to placebo. DAROL is assessing real-world outcomes with darolutamide in patients with nmCRPC. At the ESMO 2025 annual meeting, Dr. Almeida Luz reported results from the fourth prespecified interim analysis of DAROL in the context of ARAMIS.
DAROL is an ongoing, global, single-arm, non-interventional study in patients with nmCRPC for whom the decision to use darolutamide was made pre-enrollment. The primary endpoint is safety. Secondary endpoints include overall survival, metastasis free survival, PSA progression, and PSA response:
The fourth prespecified interim analysis was conducted when 799 patients completed ≥12 months of treatment (data cut-off July 8, 2024). All comparisons between DAROL and ARAMIS are descriptive in nature.
In DAROL versus ARAMIS, the median age was higher, proportionally more patients were from Asia, 6% of patients had ECOG performance status 2 or 3 (ARAMIS 0%), more patients had Gleason score ≥8, baseline PSA was lower, and fewer patients had PSA doubling time ≤6 months:
The median follow-up in DAROL was 22.5 months (IQR 16.4-29.7), and the median treatment duration was 18.0 months (IQR 10.9-26.2). By comparison, the median follow-up in the ARAMIS primary analysis was 17.9 months, and median treatment duration was 14.8 months. Most treatment emergent adverse events in DAROL and ARAMIS were grade 1/2; <20% of treatment emergent adverse events in DAROL were serious, discontinuation due to treatment emergent adverse events was similar (9% versus 9%), and fatigue was the only treatment emergent adverse event >10% (16% versus 12%):
DAROL at the fourth prespecified interim analysis indicates effectiveness in the real-world setting, consistent with ARAMIS. Overall survival, metastasis free survival, and time to mCRPC medians have not been reached, and median time to PSA progression was 38.2 months (95% CI 26.5 – not reached):
The proportion of patients with >= 90% reduction in PSA from baseline was higher in DAROL at the time of the fourth prespecified interim analysis versus ARAMIS:
In the DAROL fourth prespecified interim analysis, health related quality of life was generally good at baseline and remained stable or improved during up to 3 years of treatment with darolutamide for most patients:
Dr. de Almeida Luz concluded this presentation discussing results from a prespecified interim analysis of the DAROL prospective observational study assessing real-world experience with darolutamide in patients with nmCRPC, with the following take home points:
- The findings from DAROL fourth prespecified interim analysis indicates low incidences of treatment emergent adverse events, with no new safety signals
- Secondary outcomes, including overall survival, metastasis free survival, and prostate-specific antigen outcomes, support the effectiveness of darolutamide in real-world conditions, with health related quality of life remaining stable or improving
- The DAROL fourth prespecified interim analysis represents a varied and clinically diverse population of patients with nmCRPC in real-world conditions and supports the established efficacy and safety profiles demonstrated in ARAMIS
- DAROL is ongoing: the last patient visit is anticipated in July 2026, with the final analysis reported in 2027
Presented by: Murilo de Almeida Luz, MD, Hospital Erasto Gaertner, Curitiba, Brazil
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 European Society for Medical Oncology (ESMO) Annual Congress, Berlin, Germany, October 17–21, 2025
References:
- Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic castration-resistant prostate cancer. N Engl J Med. 2019;380(13):1235-1246.
- Fizazi K, Shore N, Tammela TL, et al. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020 Sep 10;383(11):1040-1049.