PMID- 32765070
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240329
IS  - 1179-1322 (Print)
IS  - 1179-1322 (Electronic)
IS  - 1179-1322 (Linking)
VI  - 12
DP  - 2020
TI  - Darolutamide: An Evidenced-Based Review of Its Efficacy and Safety in the 
      Treatment of Prostate Cancer.
PG  - 5667-5676
LID - 10.2147/CMAR.S227583 [doi]
AB  - Men treated with androgen deprivation therapy for rising PSA after failed local 
      therapy will often develop castrate resistance, and the appearance of metastases 
      predicts a poor prognosis. Thus, researchers have long sought to prolong the 
      onset of metastasis in patients with nonmetastatic castration-resistant prostate 
      cancer (CRPC). Until 2018, patients in this group had no FDA-approved treatment 
      options. They were typically managed with androgen-deprivation therapy (ADT) to 
      maintain castrate systemic testosterone levels and given approved therapies for 
      metastatic CRPC once metastases appeared. However, third-generation androgen 
      receptor inhibitors (ARIs) have dramatically changed the treatment paradigm, 
      having shown the ability to extend metastasis-free survival (MFS) significantly 
      over ADT alone in Phase 3 trials. The newest of these, darolutamide, prolonged 
      MFS 22 months over placebo while also improving a host of secondary and 
      exploratory endpoints such as overall survival (OS), prostate-specific antigen 
      (PSA) progression and time to pain progression, chemotherapy initiation, and 
      symptomatic skeletal events. Among third-generation ARIs, darolutamide is unique 
      in that it incorporates two pharmacologically active diastereomers and has 
      demonstrated resistance to all known androgen receptor (AR) mutations. 
      Additionally, patients taking darolutamide appear to experience comparatively few 
      central nervous system-related adverse events (AEs) such as fatigue and falls, 
      and no increases in seizures have been reported in the drug's clinical or 
      preclinical development. Various authors attribute the low incidence of 
      CNS-related AEs to darolutamide's minimal penetration of the blood-brain barrier 
      (BBB). Other side effects ranging from hot flashes to hypothyroidism also 
      occurred at rates similar to those of the placebo arm in Phase 3. As ADT in 
      itself raises cardiovascular risk, the cardiovascular safety of third-generation 
      antiandrogens as a category warrants continued scrutiny. In total, however, 
      published data suggest that darolutamide provides a reasonable option for 
      patients with nonmetastatic CRPC. Ongoing research will determine darolutamide's 
      potential role in additional disease states such as localized and 
      castration-sensitive PCa.
CI  - (c) 2020 Crawford et al.
FAU - Crawford, E David
AU  - Crawford ED
AD  - Department of Urology, University of California at San Diego, La Jolla, CA, USA.
FAU - Stanton, Whitney
AU  - Stanton W
AUID- ORCID: 0000-0002-4134-7495
AD  - Department of Pathology, University of Colorado School of Medicine, Aurora, CO, 
      USA.
FAU - Mandair, Divneet
AU  - Mandair D
AD  - Department of Pathology, University of Colorado School of Medicine, Aurora, CO, 
      USA.
AD  - Division of Internal Medicine, University of Colorado School of Medicine, Aurora, 
      CO, USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200713
PL  - New Zealand
TA  - Cancer Manag Res
JT  - Cancer management and research
JID - 101512700
PMC - PMC7367726
OTO - NOTNLM
OT  - androgen deprivation therapy
OT  - androgen receptor inhibitors
OT  - darolutamide
OT  - nonmetastatic castration-resistant prostate cancer
COIS- Dr Crawford is a consultant, advisor, meeting participant, and lecturer for 
      Bayer; a consultant or advisor for Dendreon, Ferring, Genomic Health, Janssen, 
      MDxHealth, and Tolmar; a meeting participant or lecturer for Astellas and Pfizer; 
      and a clinical investigator for the University of Colorado Cancer Center and the 
      National Institutes of Health. Dr Mandair and Ms Stanton report no relevant 
      financial interests.
EDAT- 2020/08/09 06:00
MHDA- 2020/08/09 06:01
PMCR- 2020/07/13
CRDT- 2020/08/09 06:00
PHST- 2020/04/10 00:00 [received]
PHST- 2020/06/12 00:00 [accepted]
PHST- 2020/08/09 06:00 [entrez]
PHST- 2020/08/09 06:00 [pubmed]
PHST- 2020/08/09 06:01 [medline]
PHST- 2020/07/13 00:00 [pmc-release]
AID - 227583 [pii]
AID - 10.2147/CMAR.S227583 [doi]
PST - epublish
SO  - Cancer Manag Res. 2020 Jul 13;12:5667-5676. doi: 10.2147/CMAR.S227583. 
      eCollection 2020.