Efficacy and safety of darolutamide and ADT in patient subgroups by baseline comorbidities and concomitant medications: ARANOTE post hoc analyses.

178 Background: Darolutamide (DARO) + androgen deprivation therapy (ADT) significantly improved radiological progression-free survival (rPFS) vs placebo (PBO) + ADT (HR 0.54, 95% CI 0.41–0.71; P4 comorbid or conmeds. An rPFS benefit for DARO vs PBO was seen across all comorbid (≤4, HR 0.46, 95% CI 0.32–0.65; >4, HR 0.58, 95% CI 0.36–0.93) and conmed (≤4, HR 0.48, 95% CI 0.32–0.72; >4, HR 0.61, 95% CI 0.38–0.97) subgroups. When analyzing specific comorbidities reported at BL that are commonly associated with mHSPC and older age, DARO showed a consistent rPFS benefit compared with PBO, including in pts with/without metabolic (n=185/415), cardiovascular (n=372/228), renal or urinary (n=237/363), gastrointestinal (n=113/487), and musculoskeletal (n=190/410) disorders (HR range: 0.35–0.62). With DARO, the rPFS benefit was similar in pts with cardiovascular disorders with or without corresponding conmeds (HR 1.07, 95% CI 0.58–1.94) and in pts with metabolic disorders with or without corresponding conmeds (HR 0.83, 95% CI 0.42–1.64). TEAEs, including those commonly associated with androgen receptor inhibitors and ADT, were generally similar between DARO vs PBO across comorbid (grade 3–5; ≤4, 34.1% vs 32.8%; >4, 38.4% vs 43.4%), and conmed subgroups (grade 3–5; ≤4, 33.5% vs 34.7%; >4, 39.4% vs 48.6%). Discontinuations due to TEAEs in the DARO group were lower vs PBO for all pts in both the comorbid (≤4; 4.7% vs 6.3%; >4, 8.0% vs 15.8%) and conmed (≤4; 3.3% vs 6.9%; >4, 8.8% vs 16.2%) subgroups. Conclusions: Overall, DARO demonstrated rPFS efficacy, regardless of comorbid or conmeds reported at BL, including pts with cardiovascular or metabolic disorders, with or without corresponding conmeds. DARO was well tolerated across all subgroups, with no new safety signals, supporting the use of DARO in mHSPC, even in pts with substantial comorbidities and greater use of concomitant medication. Clinical trial information: NCT04736199 .