Darolutamide Plus Androgen-deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer by Disease Volume and Risk Subgroups in the Phase 3 ARANOTE Trial
Published report from the ARANOTE trial registered as NCT04736199, in European Urology (2026), chosen as the most cited paper whose own text cites the registry id.
Overview
In ARANOTE (NCT04736199), darolutamide plus androgen-deprivation therapy (ADT) significantly reduced the risk of radiologic progression or death versus placebo plus ADT in patients with metastatic hormone-sensitive prostate cancer, with favorable safety. Here, we report on post hoc outcomes by disease volume/risk. Randomized patients received darolutamide plus ADT or placebo plus ADT (2:1). High-volume (HV) and high-risk (HR) disease were defined by the CHAARTED and LATITUDE criteria, respectively. End points included radiologic progression-free survival (primary; rPFS), time to initiation of subsequent systemic anticancer therapy, time to metastatic castration-resistant prostate cancer, time to prostate-specific antigen (PSA) progression, time to pain progression, PSA <0.2 ng/ml rates, overall survival, and safety. Of 669 patients, 472 had HV disease, 197 had low-volume (LV) disease, 400 had HR disease, and 269 had low-risk (LR) disease; baseline characteristics were generally balanced. Darolutamide consistently reduced the rPFS (HV: 40% [hazard ratio, 0.60; 95% confidence interval, 0.44 to 0.80]; LV: 70% [0.30; 0.15 to 0.60]; HR: 39% [0.61; 0.44 to 0.86]; LR: 60% [0.40; 0.25 to 0.62]), with similar trends for all secondary end points versus placebo. Treatment-emergent adverse events were similar between treatment arms across all subgroups. Darolutamide was well tolerated, and outcomes were improved versus placebo, regardless of disease volume/risk. Prior presentation: Presented at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, February 13-15, 2025. Clinical trial registration: NCT04736199 (EudraCT 2020-003093-48).
Indexed on Europe PMC as PubMed record 42586872 (DOI 10.1016/j.eururo.2026.07.026). Its abstract cites the registry id NCT04736199, which is how it was matched to this trial; no figure has been checked by an editor.
This is the paper Europe PMC returns for registry id NCT04736199 with the most citations, so it is the natural first reading for anyone following the ARANOTE trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.