Darolutamide plus androgen deprivation therapy (ADT) significantly improved radiological progression-free survival (rPFS) versus ADT in ARANOTE (NCT04736199). Here we report prostate-specific antigen (PSA) responses and their correlation with clinical outcomes.
Patients with metastatic hormone-sensitive prostate cancer were randomized to darolutamide 600 mg twice daily or placebo plus ADT. The proportion of patients achieving undetectable PSA (<0.2 ng/ml) and ultra-low PSA (<0.02 ng/ml) were determined overall and by baseline PSA category. A post hoc analysis was conducted to identify any correlation of rPFS, overall survival (OS), time to metastatic castration-resistant prostate cancer (mCRPC), and time to PSA progression with PSA responses and baseline PSA using an unstratified Cox regression model.
The rate of achievement of PSA <0.2 ng/ml and of PSA <0.02 ng/ml at any time was threefold greater (63% vs 18%) and fivefold greater (43% vs 7.8%), respectively, in the darolutamide arm versus the placebo arm, with a consistent effect across baseline PSA subgroups. Depending on baseline PSA, up to 88% of patients treated with darolutamide achieved undetectable PSA and up to 69% achieved ultra-low PSA. Achievement of PSA <0.2 ng/ml versus ≥0.2 ng/ml was associated with much better rPFS, OS, time to mCRPC, and PSA progression, with hazard ratios of 0.19 (95% confidence interval [CI] 0.13-0.27), 0.14 (95% CI 0.09-0.21), 0.16 (95% CI 0.12-0.23), and 0.08 (95% CI 0.05-0.12), respectively.
Darolutamide resulted in deep and durable PSA responses, regardless of baseline PSA. A deep PSA response was associated with better clinical outcomes, and patients reaching ultra-low PSA had the greatest clinical benefits from darolutamide.
European urology oncology. 2025 Aug 21 [Epub ahead of print]
Fred Saad, Alberto Briganti, Kunhi Parambath Haresh, Egils Vjaters, David Olmos, Natasha Littleton, Isabella Testa, Shankar Srinivasan, Frank Verholen, Neal Shore
University of Montreal Hospital Center, Montreal, Québec, Canada. Electronic address: ., Vita-Salute University San Raffaele, Milan, Italy., All India Institute of Medical Sciences, New Delhi, India., P. Stradinš Clinical University Hospital, Riga, Latvia., Department of Medical Oncology, Instituto de Investigación Sanitaria Hospital 12 de Octubre, Hospital Universitario 12 de Octubre, Madrid, Spain., Bayer Ltd., Dublin, Ireland., Bayer S.p.A., Milan, Italy., Bayer HealthCare, Whippany, NJ, USA., Bayer Consumer Care AG, Basel, Switzerland., Carolina Urologic Research Center and AUC Urology Specialists, Myrtle Beach, SC, USA.