Darolutamide (AR antagonist) + ADT cuts rPFS risk across high- and low-volume mHSPC in ARANOTE

Darolutamide is an oral androgen-receptor inhibitor evaluated with androgen-deprivation therapy (ADT) vs placebo + ADT in the Phase 3 ARANOTE trial (NCT04736199) in metastatic hormone-sensitive prostate cancer (n=669; 2:1 randomization), with this post hoc analysis stratifying outcomes by CHAARTED disease volume and LATITUDE risk. Darolutamide improved radiologic progression-free survival in every subgroup: high-volume HR 0.60 (95% CI 0.44–0.80; 40% risk reduction), low-volume HR 0.30 (0.15–0.60; 70% reduction), high-risk HR 0.61 (0.44–0.86; 39% reduction), and low-risk HR 0.40 (0.25–0.62; 60% reduction), with “similar trends” across secondary endpoints (time to subsequent systemic therapy, time to mCRPC, PSA and pain progression, PSA <0.2ng/mL rates, OS). Safety was reported as similar between arms across all subgroups—directionally consistent with ARANOTE’s overall population rPFS benefit (HR 0.54; median rPFS not reached vs 25 months) and in the broader mHSPC landscape where AR pathway intensification plus ADT has produced large rPFS gains vs ADT alone (e.g., abiraterone + prednisone + ADT in LATITUDE: median rPFS 33.0 vs 14.8 months; HR 0.47; apalutamide + ADT in TITAN: 24-month rPFS 68.2% vs 47.5%; HR 0.48).