Efficacy and safety outcomes of darolutamide in patients with non-metastatic castration-resistant prostate cancer with comorbidities and concomitant medications from the randomised phase 3 ARAMIS trial

PurposeIn patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in the Androgen Receptor Antagonizing Agent for Metastasis-free Survival (ARAMIS) trial, darolutamide significantly improved median metastasis-free survival by nearly 2 years and reduced the risk of death by 31% versus placebo, with a favourable safety/tolerability profile. This post hoc analysis of ARAMIS evaluated efficacy and safety in patients by number of comorbidities and concomitant medications.MethodsPatients with nmCRPC were randomised 2:1 to darolutamide (n = 955) or placebo (n = 554) while continuing androgen-deprivation therapy. Overall survival (OS) and treatment-emergent adverse events (TEAEs) were evaluated in subgroups by median numbers of ongoing comorbidities and concomitant medications. HRs were determined from univariate analysis using Cox regression.FindingsMedian numbers of comorbidities and concomitant medications were 6 and 10, respectively, with 41.6% of patients having >6 comorbidities and 48.8% taking >10 concomitant medications. For patients with ≤ 6 and >6 comorbidities, darolutamide increased OS versus placebo (hazard ratio [HR] 0.65 and 0.73, respectively), and this benefit was consistent for cardiovascular, metabolic, and other comorbidities (HR range: 0.39–0.88). For patients taking ≤ 10 and >10 concomitant medications, increased OS was also observed with darolutamide versus placebo (HR 0.76 and 0.66, respectively), and the benefit was consistent across medication classes (HR range: 0.45–0.80). Incidences of TEAEs and TEAEs leading to treatment discontinuation with darolutamide were similar to placebo across subgroups by numbers of comorbidities and concomitant medications.ConclusionsThe OS benefit and safety of darolutamide remained consistent with that observed in the overall ARAMIS population, even in patients with high numbers of comorbidities or concomitant medications.ClinicalTrials.gov registrationNCT02200614.Tweetable abstractDarolutamide increased overall survival versus placebo, and incidences of most adverse events were similar between treatments in patients with ≤ 6 or >6 comorbidities and those taking ≤ 10 or >10 concomitant medications.