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
Abstract
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…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
Read the paper
Related studies
- Induced osteoblast differentiation by amide derivatives of stilbene: The possible osteogenic agents
- On model selections for repeated measurement data in clinical studies
- Regulation of GLUT transporters by flavonoids in androgen-sensitive and -insensitive prostate cancer cells
- Region-specific microRNA signatures in the human epididymis
- Synthesis, biological evaluation and molecular docking of 4-Amino-2H-benzo[h]chromen-2-one (ABO) analogs containing the piperazine moiety
- In Vitro characterization of the endocrine disrupting effects of per- and poly-fluoroalkyl substances (PFASs) on the human androgen receptor
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.