(UroToday.com) The 2025 Western Section AUA annual meeting featured a prostate cancer session and a presentation by Dr. David Crawford discussing efficacy and safety by disease volume in ARANOTE. In the phase 3 ARANOTE study, patients with metastatic hormone-sensitive prostate cancer (mHSPC) receiving darolutamide + ADT experienced a 46% reduction in radiological progression or death when compared with those receiving placebo + ADT (HR 0.54; 95% CI 0.41–0.71; p<0.0001).1
The incidence of treatment-emergent adverse events was low and similar between arms, with fewer patients discontinuing study drug due to treatment-emergent adverse events in the darolutamide versus placebo arm (6.1% versus 9.0%). At the 2025 Western Section AUA annual meeting, Dr. Crawford and colleagues reported the efficacy and safety by disease volume in ARANOTE.
Patients were randomized 2:1 to darolutamide 600 mg twice daily + ADT or placebo + ADT. High-volume disease was defined by CHAARTED criteria (>4 bone metastases with at least one beyond the axial skeleton or any visceral metastases). The primary endpoint was radiological progression-free survival, and secondary endpoints included time to metastatic castration-resistant prostate cancer (mCRPC), time to PSA progression, and safety.
Of 669 patients, 472 (71%; darolutamide n = 315; placebo n = 157) had high volume disease, and 197 (29%; darolutamide n = 131; placebo n = 66) had low volume disease. Baseline demographics and patient characteristics were generally balanced between the treatment arms in the high-volume and low-volume subgroups. Patients with low volume disease had better prognostic factors (ie. a higher proportion of patients with ECOG PS 0, Gleason <8, having received prior local therapy, and lower baseline median PSA levels):
Darolutamide + ADT improved radiological progression-free survival and secondary endpoints versus placebo + ADT in both high-volume and low-volume subgroups. In the low volume subgroup, darolutamide + ADT reduced the risk of radiological progression or death by 70% (HR 0.30, 95% CI 0.15–0.60), where median radiological progression-free survival was not reached in either group. In the high volume subgroup, darolutamide + ADT reduced the risk of radiological progression or death by 40% (HR 0.60, 95% CI 0.44–0.80), with a median radiological progression-free survival of 30.2 months with darolutamide versus 19.2 months with placebo:
For the secondary endpoints, darolutamide delayed time to CRPC (high volume: HR 0.46, 95% CI 0.36–0.60; low volume: HR 0.21, 95% CI 0.12–0.37) and time to PSA progression (high volume: HR 0.34, 95% CI 0.25–0.46; low volume: HR 0.19, 95% CI 0.10–0.37):
Incidents of severe treatment-emergent adverse events were similar between treatment groups in the high-volume and low-volume subgroups. Lower rates of treatment discontinuation due to treatment-emergent adverse events with darolutamide (3.1%) versus placebo (10.8%) were observed in the low volume subgroup:
Dr. Crawford concluded his presentation discussing efficacy and safety by disease volume in ARANOTE with the following take-home points:
- In patients with mHSPC in the ARANOTE study, efficacy outcomes with darolutamide + ADT were improved versus placebo + ADT, regardless of disease volume
- Darolutamide + ADT was well-tolerated in both volume subgroups with low treatment discontinuation rates, consistent with the overall population and reconfirming the established tolerability of darolutamide as observed in the ARAMIS and ARASENS trials
- Patients with low-volume mHSPC had marked treatment efficacy with minimal treatment burden
Presented by: E. David Crawford, MD, Urologist, Professor of Urology, Jack A. Vickers Director of Prostate Cancer Research, University of California, San Diego, San Diego Health, San Diego, CA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 Western Section American Urological Association (AUA) Annual Meeting, Napa Valley, CA, Sun, Nov 2 – Thurs, Nov 6, 2025.
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