Darolutamide (AR antagonist) + ADT drives deep PSA suppression across older/comorbid mHSPC subgroups

Darolutamide (DARO), an androgen receptor inhibitor, was evaluated with androgen deprivation therapy (ADT) vs placebo + ADT in the Phase 3 ARANOTE trial (NCT04736199) in metastatic hormone-sensitive prostate cancer (mHSPC), with these post hoc analyses stratified by age, baseline comorbidity burden, and concomitant medications (DARO n=446; placebo n=223). PSA <0.2ng/mL at any time was consistently more frequent with DARO vs placebo across age (<65: 62% vs 21%; 65–74: 62% vs 21%; ≥75: 64% vs 12%), comorbidities (<5: 66% vs 21%; ≥5: 66% vs 14%), and concomitant meds (<5: 67% vs 22%; ≥5: 62% vs 16%); among those who achieved PSA <0.2ng/mL, PSA progression was 8% with DARO vs 33% with placebo, and median time to PSA progression was 421 vs 256 days. In context, ADT alone is a suboptimal modern approach in mHSPC (current standards typically intensify ADT with an AR pathway inhibitor and/or docetaxel), so these PSA gains vs ADT monotherapy align with the broader shift away from ADT-only backbones; ARANOTE’s primary endpoint also showed improved rPFS with DARO + ADT (HR 0.54).