Surgery with or Without Darolutamide in High-risk and/or Locally Advanced Prostate Cancer: The SUGAR (CCAFU-PR2) Phase 2 Trial Rationale and Protocol.
Darolutamide monotherapy
Neoadjuvant treatment
Pathological response
Progression-free survival
Prostate cancer
Radical prostatectomy
Journal
European urology oncology
ISSN: 2588-9311
Titre abrégé: Eur Urol Oncol
Pays: Netherlands
ID NLM: 101724904
Informations de publication
Date de publication:
06 Oct 2023
06 Oct 2023
Historique:
received:
08
09
2023
accepted:
25
09
2023
medline:
9
10
2023
pubmed:
9
10
2023
entrez:
8
10
2023
Statut:
aheadofprint
Résumé
High-risk prostate cancer (PCa) patients frequently experience recurrence and progression after radical prostatectomy (RP). Neoadjuvant androgen deprivation therapy (ADT) has not demonstrated a clear oncological benefit and is not currently recommended. The SUGAR trial is the first phase 2, randomised, controlled, multicentre, noncommercial, open-label study investigating single-agent perioperative darolutamide compared with the standard of care (ie, upfront RP, without neoadjuvant ADT). SUGAR aims to randomise 240 men affected by nonmetastatic PCa, with the major eligibility criteria being International Society of Urological Pathology grade group ≥4, seminal vesicle invasion at magnetic resonance imaging and/or clinically node-positive disease. Patients in the experimental arm will undergo neoadjuvant darolutamide monotherapy, RP, and adjuvant darolutamide, completing 9 mo of treatment. The primary endpoint is noncurable recurrence-free survival, an innovative and clinically meaningful measure; the secondary endpoints encompass safety; recurrence-free, metastasis-free, and overall survival; pathological response; and quality of life. A predictive biomarker analysis will also be performed. Initial data suggest that intensified neoadjuvant treatment with androgen receptor signalling inhibitors (ARSIs) is associated with a sustained pathological response and may improve outcomes, via tumour downstaging and micrometastasis eradication. ARSI monotherapy could further enhance tolerability. SUGAR will provide efficacy and safety information on perioperative darolutamide monotherapy compared with upfront RP, in a contemporary high-risk PCa population undergoing surgery. The on-going SUGAR clinical trial evaluates 9 mo of darolutamide treatment in addition to radical prostatectomy, in men affected by prostate cancer with specific high-risk characteristics. It investigates whether this hormonal treatment can lower the rates of noncurable recurrences, maintaining a favourable tolerability profile.
Sections du résumé
BACKGROUND
BACKGROUND
High-risk prostate cancer (PCa) patients frequently experience recurrence and progression after radical prostatectomy (RP). Neoadjuvant androgen deprivation therapy (ADT) has not demonstrated a clear oncological benefit and is not currently recommended.
OBJECTIVE
OBJECTIVE
The SUGAR trial is the first phase 2, randomised, controlled, multicentre, noncommercial, open-label study investigating single-agent perioperative darolutamide compared with the standard of care (ie, upfront RP, without neoadjuvant ADT).
DESIGN, SETTING, AND PARTICIPANTS
METHODS
SUGAR aims to randomise 240 men affected by nonmetastatic PCa, with the major eligibility criteria being International Society of Urological Pathology grade group ≥4, seminal vesicle invasion at magnetic resonance imaging and/or clinically node-positive disease. Patients in the experimental arm will undergo neoadjuvant darolutamide monotherapy, RP, and adjuvant darolutamide, completing 9 mo of treatment.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
METHODS
The primary endpoint is noncurable recurrence-free survival, an innovative and clinically meaningful measure; the secondary endpoints encompass safety; recurrence-free, metastasis-free, and overall survival; pathological response; and quality of life. A predictive biomarker analysis will also be performed.
RESULTS AND LIMITATIONS
CONCLUSIONS
Initial data suggest that intensified neoadjuvant treatment with androgen receptor signalling inhibitors (ARSIs) is associated with a sustained pathological response and may improve outcomes, via tumour downstaging and micrometastasis eradication. ARSI monotherapy could further enhance tolerability.
CONCLUSIONS
CONCLUSIONS
SUGAR will provide efficacy and safety information on perioperative darolutamide monotherapy compared with upfront RP, in a contemporary high-risk PCa population undergoing surgery.
PATIENT SUMMARY
RESULTS
The on-going SUGAR clinical trial evaluates 9 mo of darolutamide treatment in addition to radical prostatectomy, in men affected by prostate cancer with specific high-risk characteristics. It investigates whether this hormonal treatment can lower the rates of noncurable recurrences, maintaining a favourable tolerability profile.
Identifiants
pubmed: 37806843
pii: S2588-9311(23)00212-2
doi: 10.1016/j.euo.2023.09.020
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.