Abstract

Background: Darolutamide plus androgen‐deprivation therapy (ADT) improved metastasis‐free survival (MFS) by 2 years and reduced the risk of death by 31% in nonmetastatic castration‐resistant prostate cancer (nmCRPC) in ARAMIS. Prior local therapy may influence the efficacy of subsequent systemic therapy. This post hoc analysis of ARAMIS evaluated the effect of prior local therapy on the efficacy and health‐related quality of life (HRQoL) of darolutamide. Methods: Patients with nmCRPC were randomized to darolutamide (n = 955) or placebo (n = 554) while continuing ADT. MFS, overall survival (OS), time to prostate‐specific antigen (PSA) progression, and HRQoL deterioration‐free survival (DetFS) were estimated for patients with and without local therapy and by treatment using Kaplan–Meier methods. Results: Darolutamide increased MFS versus placebo in patients with (HR, 0.36; 95% CI, 0.26–0.48) and without (HR, 0.46; 95% CI, 0.36–0.59) local therapy. Median OS was 48.6 months for placebo without local therapy and not reached in either the darolutamide group or placebo group with local therapy. Darolutamide 3‐year OS rates were 86.9% (95% CI, 83.0–90.8) and 79.0% (95% CI, 66.2–78.1) in patients with and without local therapy, respectively. Darolutamide showed evidence of improved OS versus placebo in patients with prior local therapy (HR, 0.80; 95% CI, 0.50–1.30) and a greater effect in those without local therapy (HR, 0.67; 95% CI, 0.50–0.90). Darolutamide delayed time to PSA progression and HRQoL deterioration regardless of local therapy. Conclusions: Darolutamide versus placebo improved MFS, OS, time to PSA progression, and HRQoL DetFS independent of prior local therapy, consistent with the overall ARAMIS population. Trial Registration: ClinicalTrials.gov registration: NCT02200614