Dr Carles Galceran on the Safety of Darolutamide with ADT and Docetaxel in Older Patients With mHSPC

"I do not think that [adding] darolutamide [to androgen deprivation therapy and docetaxel] increases the risk of stopping or interrupting the treatment."

Joan Carles Galceran, MD, PhD, an associate professor of medicine at the Hospital Universitari Vall d’Hebron, discussed safety findings from an age-based subgroup analysis from the phase 3 ARASENS trial (NCT02799602), which evaluated darolutamide (Nubeqa) in combination with androgen deprivation therapy (ADT) and docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

The ARASENS trial enrolled patients with mHSPC who were candidates for upfront docetaxel-based chemotherapy plus ADT and had an ECOG performance status of 0 or 1. Patients were randomly assigned to receive darolutamide or placebo in combination with ADT and 6 cycles of docetaxel. The subgroup analysis assessed outcomes in patients younger than 75 years of age and those 75 years of age or older to evaluate whether efficacy and tolerability varied.

Results demonstrated consistent efficacy across both age subgroups. Darolutamide plus ADT and docetaxel was associated with improved overall survival (OS) compared with the placebo regimen in patients under 75 years of age (HR, 0.70; 95% CI, 0.58-0.84) and those 75 years of age or older (HR, 0.61; 95% CI, 0.41-0.91). Time to castration-resistant disease (mCRPC) was also prolonged with the experimental regimen in both the younger group (HR, 0.35; 95% CI, 0.30-0.43) and older group (HR, 0.42; 95% CI, 0.28-0.64).

Regarding safety, the darolutamide regimen was comparable with the placebo regimen; treatment-emergent adverse effects were more common in the older cohort, which aligned with the subgroup’s increased comorbidities. Carles Galceran noted that the addition of darolutamide did not appear to increase the risk of treatment discontinuation, irrespective of age. In patients under 75 years of age, 89% of patients in the experimental arm completed 6 cycles of docetaxel compared with 88% of patients in the placebo group. In the subgroup of patients 75 years of age or older, these respective rates were 80% and 76%. The median duration of treatment in the younger subgroup was 41.2 months for the darolutamide regimen vs 16.8 months for the placebo regimen. In the older subgroup, the median treatment duration was 38.5 months for the experimental regimen vs 15.0 months for the control regimen.