PMID- 36087070
OWN - NLM
STAT- MEDLINE
DCOM- 20230323
LR  - 20230323
IS  - 1464-410X (Electronic)
IS  - 1464-4096 (Linking)
VI  - 131
IP  - 4
DP  - 2023 Apr
TI  - Impact of darolutamide on local symptoms: pre-planned and post hoc analyses of 
      the ARAMIS trial.
PG  - 452-460
LID - 10.1111/bju.15887 [doi]
AB  - OBJECTIVE: To assess, the effect of darolutamide (a structurally distinct 
      androgen receptor inhibitor) on urinary and bowel symptoms, using data from the 
      phase III ARAMIS trial (NCT02200614) that showed darolutamide significantly 
      reduced the risk of metastasis and death versus placebo. PATIENTS AND METHODS: 
      Patients with non-metastatic castration-resistant prostate cancer (nmCRPC) were 
      randomised 2:1 to darolutamide (n = 955) or placebo (n = 554). Local symptom 
      control was assessed by first prostate cancer-related invasive procedures and 
      post hoc analyses of time to deterioration in quality of life (QoL) using total 
      urinary and bowel symptoms, and individual questions for these symptoms from the 
      European Organisation for Research and Treatment of Cancer Quality of Life 
      Questionnaire Prostate Cancer Module subscales and Functional Assessment of 
      Cancer Therapy-Prostate prostate cancer subscale. Prostate-specific antigen (PSA) 
      responses were correlated with urinary and bowel adverse events (AEs). RESULTS: 
      Fewer patients receiving darolutamide (4.7%) versus placebo (9.6%) underwent 
      invasive procedures, and time to first procedure was prolonged with darolutamide 
      (hazard ratio 0.42, 95% confidence interval 0.28-0.62). Darolutamide 
      significantly (P < 0.01) delayed worsening of QoL for total urinary and bowel 
      symptoms versus placebo, mostly attributed by individual symptoms of urinary 
      frequency, associated pain, and interference with daily activities. AEs of 
      urinary retention and dysuria were less frequent with darolutamide, and greater 
      PSA response (>/=90%, >/=50% and <90%, <50%) among darolutamide-treated patients was 
      associated with lower incidences of urinary retention (2.2%, 4.2%, 5.1%) and 
      dysuria (0.5%, 3.2%, 5.1%), respectively. CONCLUSIONS: Darolutamide demonstrated 
      a positive impact on local disease recurrence and symptom control in patients 
      with nmCRPC, delayed time to deterioration in QoL related to urinary and bowel 
      symptoms, and a favourable safety profile showing similar incidence of urinary- 
      and bowel-related AEs compared with placebo.
CI  - (c) 2022 The Authors. BJU International published by John Wiley & Sons Ltd on 
      behalf of BJU International.
FAU - Shore, Neal D
AU  - Shore ND
AUID- ORCID: 0000-0001-5767-0548
AD  - Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC, 
      USA.
FAU - Stenzl, Arnulf
AU  - Stenzl A
AUID- ORCID: 0000-0003-4207-9928
AD  - Clinic for Urology Tubingen, Tubingen, Germany.
FAU - Pieczonka, Christopher
AU  - Pieczonka C
AD  - Associated Medical Professionals, Syracuse, NY, USA.
FAU - Klaassen, Zachary
AU  - Klaassen Z
AD  - Georgia Cancer Center, Augusta, GA, USA.
FAU - Aronson, William J
AU  - Aronson WJ
AD  - University of California and VA Medical Center Greater Los Angeles Healthcare 
      System, Los Angeles, CA, USA.
FAU - Karsh, Lawrence
AU  - Karsh L
AD  - The Urology Center of Colorado, Denver, CO, USA.
FAU - Ryan, Charles J
AU  - Ryan CJ
AD  - University of Minnesota, Minneapolis, MN, USA.
FAU - Ortiz, Jorge
AU  - Ortiz J
AD  - Bayer Healthcare, Whippany, NJ, USA.
FAU - Srinivasan, Shankar
AU  - Srinivasan S
AD  - Bayer Healthcare, Whippany, NJ, USA.
FAU - Mohamed, Ateesha F
AU  - Mohamed AF
AD  - Bayer Healthcare, Whippany, NJ, USA.
FAU - Verholen, Frank
AU  - Verholen F
AD  - Bayer Consumer Care AG, Basel, Switzerland.
LA  - eng
SI  - ClinicalTrials.gov/NCT02200614
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20220929
PL  - England
TA  - BJU Int
JT  - BJU international
JID - 100886721
RN  - 0 (darolutamide)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
RN  - 0 (Androgen Receptor Antagonists)
SB  - IM
MH  - Male
MH  - Humans
MH  - *Prostatic Neoplasms, Castration-Resistant/drug therapy/pathology
MH  - Quality of Life
MH  - Prostate-Specific Antigen
MH  - Dysuria/chemically induced/drug therapy
MH  - *Urinary Retention
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - Androgen Receptor Antagonists
OTO - NOTNLM
OT  - androgen-receptor antagonist
OT  - bowel symptoms
OT  - castration-resistant prostatic neoplasms
OT  - quality of life
OT  - urinary symptoms
EDAT- 2022/09/11 06:00
MHDA- 2023/03/24 06:00
CRDT- 2022/09/10 09:52
PHST- 2022/09/11 06:00 [pubmed]
PHST- 2023/03/24 06:00 [medline]
PHST- 2022/09/10 09:52 [entrez]
AID - 10.1111/bju.15887 [doi]
PST - ppublish
SO  - BJU Int. 2023 Apr;131(4):452-460. doi: 10.1111/bju.15887. Epub 2022 Sep 29.