Darolutamide Plus Androgen-deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer by Disease Volume and Risk Subgroups in the Phase 3 ARANOTE Trial.

Abstract

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).