TY - JOUR
T1 - A Deep Prostate-specific Antigen Response to Darolutamide plus Androgen Deprivation Therapy Is Associated with Better Clinical Outcomes in the Phase 3 ARANOTE Trial in Patients with Metastatic Hormone-sensitive Prostate Cancer
AU - Saad, Fred
AU - Briganti, Alberto
AU - Haresh, Kunhi Parambath
AU - Vjaters, Egils
AU - Olmos, David
AU - Littleton, Natasha
AU - Testa, Isabella
AU - Srinivasan, Shankar
AU - Verholen, Frank
AU - Shore, Neal
N1 - Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.
PY - 2025/8/21
Y1 - 2025/8/21
N2 - BACKGROUND AND OBJECTIVE: 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.METHODS: 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.KEY FINDINGS AND LIMITATIONS: 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.CONCLUSIONS AND CLINICAL IMPLICATIONS: 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.
AB - BACKGROUND AND OBJECTIVE: 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.METHODS: 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.KEY FINDINGS AND LIMITATIONS: 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.CONCLUSIONS AND CLINICAL IMPLICATIONS: 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.
UR - https://pubmed.ncbi.nlm.nih.gov/40846621/
U2 - 10.1016/j.euo.2025.06.010
DO - 10.1016/j.euo.2025.06.010
M3 - Article
C2 - 40846621
SN - 2588-9311
JO - European urology oncology
JF - European urology oncology
ER -
