Real-world DAROL data support darolutamide use regardless of comorbidity burden

Darolutamide (Nubeqa) demonstrated maintained efficacy and acceptable tolerability in patients with non-metastatic castration-resistant prostate cancer who had significant comorbidities and concomitant medications, according to the fourth interim analysis of the DAROL real-world study (NCT04122976)—with adverse event rates higher in the high-comorbidity group but discontinuation rates remaining low across both populations.¹

In this video, recorded at the 2026 American Urological Association (AUA) Annual Meeting in Washington, DC, Murilo De Almeida Luz, MD, gave an overview of the DAROL study design and key findings.

DAROL is an ongoing international, multicenter, prospective, single-arm, noninterventional study designed to confirm in a real-world setting the findings of the phase 3 ARAMIS trial (NCT02200614), which established darolutamide's metastasis-free survival and overall survival benefits in nmCRPC. The fourth interim analysis captured data from 799 patients who had received at least 12 months of treatment, with complete data available for approximately 620 patients. The primary end point is safety; overall survival, metastasis-free survival, and time to PSA progression are secondary endpoints.

"This is a bit of a real-world trial," said Murilo De Almeida Luz, MD, a study investigator and a urologic oncologist at Mount Sinai Icahn School of Medicine in New York, New York. "The decision to start the drug was based on investigator's choice—it was not as strict and controlled as in the ARAMIS trial." That flexibility reflects the practical realities of clinical practice, including variability in imaging and patient selection criteria, while enabling prospective data collection across a broadly representative patient population.

The comorbidity analysis presented at AUA 2026 was motivated by the clinical profile of the nmCRPC population itself. Ninety-five percent of patients had at least one comorbidity, with 87% having either a comorbidity or concomitant medication ongoing at the time darolutamide was initiated. The most frequent comorbidities were hypertension (50%), hypercholesterolemia (20%), and diabetes mellitus (17%). Patients were stratified by Charlson Comorbidity Index into low-to-moderate (score ≤5) and high (score >5) groups to assess whether comorbidity burden affected safety or efficacy outcomes.

Treatment-emergent adverse events were more frequent in patients with comorbidities or concomitant medications compared to those without (66% vs. 28%; grade 3/4: 19% vs. 8%; grade 5: 4% vs. 1%). The most common TEAEs included fatigue, asthenia, hot flush, constipation, and urinary tract infection. Despite the higher adverse event rates, discontinuation due to TEAEs was similarly low across both groups—9% vs 7%.

"We do have a bit more adverse events in the high comorbidity population—that was real," De Almeida Luz said. "But the rates of discontinuation were not as high, so patients were able to stay on treatment."

Efficacy was preserved across comorbidity subgroups, though outcomes varied somewhat depending on the specific underlying conditions.

"The fact that a patient has comorbidities is not a contraindication to treatment," De Almeida Luz said. "But it is a patient that we need to keep an eye on—a bit more cautious, a bit more attention on any adverse events—because we know they'll be more prevalent in that population. That's not a reason to not treat those patients, because the efficacy was as good as for patients with a low comorbidity index."

No cumulative toxicity or new safety signals were identified after an average treatment duration of 18 months and follow-up of 22.5 months.

REFERENCE

1. Real-world darolutamide safety and effectiveness in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) with comorbidities and concomitant medications: post hoc analyses at DAROL interim analysis 4 (IA4). Presented at: 2026 American Urological Association Annual Meeting. May 15-18, 2026. Washington, DC. Abstract IP73-13. https://www.auajournals.org/doi/10.1097/01.JU.0001191728.67566.6d.13