The use of darolutamide (DARO) in addition to androgen deprivation therapy (ADT) is effective at improving radiological progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) compared with placebo plus ADT, irrespective of disease volume, according to the subanalysis of the phase III ARANOTE trial.

DARO plus ADT is also well-tolerated both in patients with high- (HV) and low-volume (LV) disease, consistent with the overall population.

Furthermore, “[p]atients with LV mHSPC had marked treatment efficacy with minimal treatment burden,” said lead author Dr Fred Saad from the University of Montreal Hospital Center, Montreal, QC, Canada, who presented the study at ASCO GU 2025.

A total of 669 mHSPC patients were included in the analysis, of whom 472 (71 percent; DARO n=315; placebo n=157) had HV disease and 197 (29 percent; DARO n=131; placebo n=66) had LV disease.

Baseline demographics and patient characteristics were similar between treatment arms in HV and LV subgroups. However, those with LV disease showed better prognostic factors (eg, a higher proportion of patients with ECOG PS 0, Gleason <8, having received prior local therapy, and lower baseline median prostate-specific antigen [PSA] levels). [ASCO GU 2025, abstract 151]

DARO plus ADT, compared with placebo plus ADT, improved rPFS in patients with either HV or LV disease. In the LV subgroup, DARO plus ADT resulted in a 70-percent reduction in the risk of radiological progression or death (hazard ratio [HR], 0.30, 95 percent confidence interval [CI], 0.15?0.60), with median rPFS not reached in either group.

Among patients with HV disease, DARO plus ADT showed a 40-percent decrease in the risk of radiological progression or death (HR, 0.60, 95 percent CI, 0.44?0.80), with median rPFS of 30.2 months with DARO compared with 19.2 percent with placebo.

Disease progression

In addition, treatment with DARO delayed the time to metastatic castration-resistant prostate cancer (mCRPC) in both subgroups (HV: HR, 0.46, 95 percent CI, 0.36?0.60; LV: HR, 0.21, 95 percent CI, 0.12?0.37), as well as time to PSA progression (HV: HR, 0.34, 95 percent CI, 0.25?0.46; LV: HR, 0.19, 95 percent CI, 0.10?0.37).

DARO also resulted in a higher proportion of patients achieving PSA <0.2 ng/mL compared with placebo (HV: 54.6 percent vs 15.5 percent; LV: 82.6 percent vs 25.4 percent) in both HV and LV subgroups.

In terms of safety, the incidence of treatment-emergent adverse events (TEAEs) was low and similar between treatment arms in both HV and LV subgroups and was consistent with the overall population. However, the rates of fatigue (2.3 percent vs 13.8 percent) and treatment discontinuation due to TEAEs (3.1 percent vs 10.8 percent) were lower with DARO versus placebo in the LV subgroup.

In this study, Saad and his team randomized mHSPC patients 2:1 to receive either DARO 600 mg twice daily plus ADT or placebo plus ADT. The primary endpoint was rPFS, while secondary outcomes were time to mCRPC, time to PSA progression, and safety.

HV disease referred to the presence of visceral metastases and/or ≥4 bone lesions with ≥1 beyond the vertebral bodies and pelvis.