Pedro Barata, MD, on darolutamide efficacy across age subgroups

The phase 3 ARANOTE trial (NCT04736199) established the efficacy of darolutamide (Nubeqa) plus androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC), showing that the combination significantly extended radiological progression-free survival (PFS) vs placebo plus ADT in this patient population. Data presented at the 2025 European Society for Medical Oncology Congress in Berlin, Germany sought to assess the differential effects of the regimen across age subgroups.

“There has been some data emerging suggesting that the benefit of adding [an] ARPI may not be the same, might be differential based on age, where elderly patients might not benefit as well as younger patients from the addition of the ARPI,” presenting author Pedro C. Barata, MD, MSc, FACP, explained during an interview with Urology Times®. He specifically cited findings from the STOPCAP study that indicated ARPIs may confer greater benefit in younger patients.²

Barata is a GU medical oncologist at University Hospitals in Cleveland, Ohio.

In the overall population, the median rPFS was not evaluable in the darolutamide arm vs 25 months in the placebo arm (HR, 0.54; 95% CI, 0.41 to 0.71; P < .0001). The benefit of darolutamide was consistent across age groups, with hazard ratios of 0.44, 0.64, and 0.51 in patients aged less than 65, 65 to 74, and 75 and older, respectively.

The authors also noted, “The incidence and severity of [treatment-emergent adverse events] TEAEs increased slightly with age, as expected, but with similar frequencies between DARO and PBO within each age subgroup.”

Discontinuation of treatment due to TEAEs ranged from 5% to 7% in the darolutamide age subgroups vs 5% to 11% among the placebo age subgroups.

REFERENCES

1. Saad F, Morgans AK, Shore ND, et al. Darolutamide efficacy, quality of life, and safety outcomes by age subgroup: ARANOTE post hoc analyses. Presented at: 2025 European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. Abstract 2459P. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2025_abstracts/2459P.html.pdf

2. Fisher D, Vale C, Rydzewska L, et al. Which patients with metastatic hormone-sensitive prostate cancer (mHSPC) benefit more from androgen receptor pathway inhibitors (ARPIs)? STOPCAP meta-analyses of individual participant data (IPD). J Clin Oncol. 43, 2025 (suppl 5; abstr 20). doi:10.1200/JCO.2025.43.5_suppl.20