Prostate-specific antigen outcomes of darolutamide and androgen deprivation therapy in patient subgroups by age, comorbidities, and concomitant medications: ARANOTE post hoc analyses.

5103 Background: Darolutamide (DARO) + androgen deprivation therapy (ADT) significantly improved radiological progression-free survival (HR 0.54, 95% CI 0.41–0.71; P<0.0001) vs placebo (PBO) + ADT in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) in the phase 3 ARANOTE (NCT04736199) trial, with a favorable safety profile. Here, we report the impact of age, comorbidities (comorbid), and use of concomitant medications (conmeds) ongoing at baseline on prostate specific antigen (PSA) outcomes in pts treated with DARO or PBO. Methods: Pts were randomized 2:1 to DARO 600 mg orally twice daily or PBO, both with ADT. Pts were grouped by age and number/type of comorbid or conmeds reported at baseline. Descriptive statistics ( post hoc ) summarized baseline demographics, disease characteristics, and PSA outcomes by age, comorbid, and conmed subgroups. Results: Baseline demographics and disease characteristics were generally similar between DARO (n=446) and PBO (n=223) across all subgroups by age (<65, 65–74, or ≥75 years [yrs]), comorbid (<5 or ≥5), and conmeds (<5 or ≥5), respectively. Rates of reaching PSA <0.2 ng/mL at any time were consistently higher with DARO vs PBO across all age (<65 yrs, 62% [n=69/112] vs 21% [n=13/63]; 65–74 yrs, 62% [n=116/187] vs 21% [n=19/89]; ≥75 yrs, 64% [n=81/126] vs 12% [n=7/59]), comorbid (<5, 66% [n=160/244] vs 21% [n=26/122]; ≥5, 66% [n=86/130] vs 14% [n=10/71]), and conmed (<5, 67% [n=115/173] vs 22% [n=21/96]; ≥5, 62% [n=93/151] vs 16% [n=11/71]) subgroups. With DARO, rates of reaching PSA <0.2 ng/mL at any time were consistent among pts with metabolic disorders with or without corresponding conmeds (71% [n=43/61] vs 69% [n=29/42]). The rate of reaching PSA <0.2 ng/ml was slightly lower in patients with cardiovascular disorders who were not receiving corresponding conmeds at baseline (51% [n=22/43]) compared with those receiving corresponding conmeds (64% [n=119/187]). A substantially lower rate of PSA progression was observed with DARO (8% [n=22/266]) vs PBO (33% [n=13/39]) among pts that reached PSA <0.2 ng/mL. Median time to PSA progression among patients that reached PSA <0.2 ng/mL was 421 days (range, 85–702) and 256 days (range, 85–514) for DARO and PBO, respectively. Conclusions: Overall, an efficacy benefit was observed with DARO, irrespective of age, and number of comorbidities or concomitant medications reported at baseline in pts with mHSPC, including those with cardiovascular or metabolic disorders, with or without corresponding conmeds, respectively. These results support the use of DARO in mHSPC, even in pts with older age, substantial comorbidities, and greater use of concomitant medications. Clinical trial information: NCT04736199 .