Deep and Durable Prostate-specific Antigen Response to Darolutamide with Androgen Deprivation Therapy and Docetaxel, and Association with Clinical Outcomes for Patients with High- or Low-volume Metastatic Hormone-sensitive Prostate Cancer: Analyses of the

Addition of darolutamide to androgen deprivation therapy (ADT) and docetaxel significantly improved overall survival (OS) in ARASENS (NCT02799602). Here we report on prostate-specific antigen (PSA) responses and their association with outcomes.

ARASENS is an international, double-blind, phase 3 study in patients with metastatic hormone-sensitive prostate cancer (mHSPC) randomized to darolutamide 600 mg orally twice daily (n = 651) or placebo (n = 654), both with ADT + docetaxel. The proportion of patients with undetectable PSA (<0.2 ng/ml) and time to PSA progression (≥25% relative and ≥2 ng/ml absolute increase from nadir) were compared between groups in prespecified exploratory analyses. PSA outcomes by disease volume and the association of undetectable PSA with OS and times to castration-resistant prostate cancer (CRPC) and PSA progression were assessed in post hoc analyses.

The proportion of patients with undetectable PSA at any time was more than doubled with darolutamide versus placebo, at 67% versus 29% in the overall population, 62% versus 26% in the high-volume subgroup, and 84% versus 38% in the low-volume subgroup. Darolutamide delayed time to PSA progression versus placebo, with hazard ratios of 0.26 (95% confidence interval [CI] 0.21-0.31) in the overall population, 0.30 (95% CI 0.24-0.37) in the high-volume subgroup, and 0.093 (95% CI 0.047-0.18) in the low-volume subgroup. Undetectable PSA at 24 wk was associated with longer OS, with a hazard ratio of 0.49 (95% CI 0.37-0.65) in the darolutamide group, as well as longer times to CRPC and PSA progression, with similar findings in the disease volume subgroups.

Darolutamide + ADT + docetaxel led to deep and durable PSA responses in patients with high- or low-volume mHSPC. Achievement of undetectable PSA (<0.2 ng/ml) was correlated with better clinical outcomes.

For patients with metastatic hormone-sensitive prostate cancer being treated with androgen deprivation therapy and docetaxel, PSA (prostate-specific antigen) became undetectable (below 0.2 ng/ml) in 67% of those also receiving darolutamide versus 29% of patients also receiving placebo. On average, patients achieving undetectable PSA lived longer than patients with detectable PSA.

European urology. 2024 Apr 20 [Epub ahead of print]

Fred Saad, Maha H A Hussain, Bertrand Tombal, Karim Fizazi, Cora N Sternberg, E David Crawford, Luke T Nordquist, Martin Bögemann, Ronald Tutrone, Neal D Shore, Laurence Belkoff, Todd Fralich, Jay Jhaveri, Shankar Srinivasan, Rui Li, Frank Verholen, Iris Kuss, Matthew R Smith

University of Montreal Hospital Center, Montreal, Canada. Electronic address: ., Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Division of Urology, IREC, Cliniques Universitaires Saint Luc, UC Louvain, Brussels, Belgium., Institut Gustave Roussy, University of Paris-Saclay, Villejuif, France., Englander Institute for Precision Medicine, Weill Cornell Department of Medicine, Meyer Cancer Center, New York-Presbyterian Hospital, New York, NY, USA., UC San Diego School of Medicine, San Diego, CA, USA., XCancer, Omaha, NE, USA., Münster University Medical Center, Münster, Germany., United Urology Group, Towson, MD, USA., Carolina Urologic Research Center and Genesis Care/Atlantic Urology Clinics, Myrtle Beach, SC, USA., MidLantic Urology, LLC, Bala Cynwyd, PA, USA., Bayer HealthCare Pharmaceuticals Inc, Whippany, NJ, USA., Bayer Consumer Care AG, Basel, Switzerland., Bayer AG, Berlin, Germany., Massachusetts General Hospital Cancer Center, Boston, MA, USA.