Age-related Efficacy and Safety of Darolutamide Plus Androgen-deprivation Therapy and Docetaxel in Patients with Metastatic Hormone-sensitive Prostate Cancer: A Subgroup Analysis of the Phase 3 ARASENS Trial

BACKGROUND AND OBJECTIVE: Prostate cancer is typically a disease of older men. As patients age, they develop comorbidities and require more medications, which may adversely affect or be affected by prostate cancer treatments. We investigated whether the survival benefits and favorable safety profile of darolutamide in the phase 3 ARASENS trial could be seen regardless of age. METHODS: Patients received darolutamide 600 mg or placebo orally twice daily plus androgen-deprivation therapy and docetaxel. Outcomes were assessed in subgroups of patients aged <75 yr (n = 1086) and ≥75 yr (n = 219). KEY FINDINGS AND LIMITATIONS: Most patients in both age groups had comorbidities (<75 yr: 94%; ≥75 yr: 97%) and concomitant medications (median 8-9). In both age subgroups, compared with placebo, darolutamide increased overall survival (<75 yr: hazard ratio 0.70 [95% confidence interval 0.58-0.84]; ≥75 yr: 0.61 [0.41-0.91]), delayed time to metastatic castration-resistant prostate cancer (<75 yr: 0.35 [0.30-0.43]; ≥75 yr: 0.42 [0.28-0.64]), and delayed time to initiation of subsequent therapy (<75 yr: 0.40 [0.34-0.48]; ≥75 yr: 0.35 [0.22-0.54]). Treatment-emergent adverse events were similar in the darolutamide/placebo groups, with slightly higher incidences in older patients. This analysis is limited by its post hoc nature. CONCLUSIONS AND CLINICAL IMPLICATIONS: In the 219 patients aged ≥75 yr in ARASENS, darolutamide demonstrated improved efficacy versus placebo and favorable safety, consistent with the findings in patients aged <75 yr. Thus, darolutamide and androgen-deprivation therapy with docetaxel can be considered a standard of care triplet therapy for metastatic hormone-sensitive prostate cancer regardless of patients' age.