PMID- 32278840
OWN - NLM
STAT- MEDLINE
DCOM- 20210818
LR  - 20210818
IS  - 1938-0682 (Electronic)
IS  - 1558-7673 (Linking)
VI  - 18
IP  - 5
DP  - 2020 Oct
TI  - A Systematic Review and Network Meta-analysis of Novel Androgen Receptor 
      Inhibitors in Non-metastatic Castration-resistant Prostate Cancer.
PG  - 343-350
LID - S1558-7673(20)30039-2 [pii]
LID - 10.1016/j.clgc.2020.02.005 [doi]
AB  - BACKGROUND: Among men with high-risk non-metastatic castrate-resistant prostate 
      cancer (nmCRPC), we used network meta-analysis to compare non-steroidal 
      anti-androgens (NSAAs) and stratified class-level meta-analysis to identify 
      subgroups with particular benefit from NSAAs with androgen deprivation therapy 
      versus androgen deprivation therapy alone. MATERIALS AND METHODS: We performed a 
      systematic review of phase III parallel-group randomized controlled trials in 
      adult men with nmCRPC. Primary outcome was metastasis-free survival (MFS). 
      Secondary outcomes included overall survival (OS), prostate-specific antigen 
      (PSA) progression-free survival (PFS), and rates of grade 3 to 4 adverse events 
      (AEs). We assessed class-level effects using random effects models; effect 
      modification owing to subgroup effects using random-effects models to pool 
      study-level differences; and comparative outcomes between agents using 
      fixed-effect network models in a Bayesian framework. RESULTS: Three randomized 
      controlled trials were identified. Pooled MFS, PSA-PFS, and OS were significantly 
      greater with NSAA versus placebo (hazard ratio [HR], 0.32; 95% confidence 
      interval [CI], 0.25-0.41; HR, 0.08; 95% CI, 0.05-0.13; and HR, 0.74; 95% CI, 
      0.61-0.90, respectively). Subgroup analysis demonstrated a greater benefit with 
      NSAAs in men with Eastern Cooperative Oncology Group performance status 0 (HR, 
      0.30; 95% CI, 0.24-0.38) versus 1 (HR, 0.45; 95% CI, 0.36-0.56; P = .005), but no 
      difference owing to PSA doubling time (P = .43) or use of osteoclast targeting 
      therapy (P = .77). Bayesian analysis showed apalutamide and enzalutamide had a 
      56% and 44% likelihood of maximizing MFS, respectively, with subgroup analysis 
      demonstrating these agents were preferred regardless of PSA doubling time and 
      performance status. There was a 44%, 41%, and 15% likelihood that apalutamide, 
      darolutamide and enzalutamide offered the greatest OS benefit, respectively. 
      Grade 3 to 4 AEs were more common with NSAAs (odds ratio [OR], 1.47; 95% CI, 
      1.27-1.71) and there was a 61% chance that darolutamide was preferred. 
      CONCLUSIONS: NSAAs improve survival in high-risk nmCRPC. Apalutamide and 
      enzalutamide may result in improved oncologic outcomes. Darolutamide may result 
      in fewer AEs. Phase IV data are needed to validate these findings.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Hird, Amanda E
AU  - Hird AE
AD  - Division of Urology, Department of Surgery, University of Toronto, Toronto, 
      Ontario, Canada.
FAU - Magee, Diana E
AU  - Magee DE
AD  - Division of Urology, Department of Surgery, University of Toronto, Toronto, 
      Ontario, Canada.
FAU - Bhindi, Bimal
AU  - Bhindi B
AD  - Division of Urology, Department of Surgery, University of Calgary, Calgary, 
      Alberta, Canada.
FAU - Ye, Xiang Y
AU  - Ye XY
AD  - MiCare Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada.
FAU - Chandrasekar, Thenappan
AU  - Chandrasekar T
AD  - Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, 
      Philadelphia, PA.
FAU - Goldberg, Hanan
AU  - Goldberg H
AD  - Division of Urology, Department of Surgery, Princess Margaret Hospital, 
      University Health Network, Toronto, Ontario, Canada.
FAU - Klotz, Laurence
AU  - Klotz L
AD  - Division of Urology, Department of Surgery, Sunnybrook Health Sciences Centre, 
      Toronto, Ontario, Canada.
FAU - Fleshner, Neil
AU  - Fleshner N
AD  - Division of Urology, Department of Surgery, Princess Margaret Hospital, 
      University Health Network, Toronto, Ontario, Canada.
FAU - Satkunasivam, Raj
AU  - Satkunasivam R
AD  - Department of Urology and Center for Outcomes Research, Houston Methodist 
      Hospital, Houston, TX.
FAU - Klaassen, Zachary
AU  - Klaassen Z
AD  - Division of Urology, Medical College of Georgia at Augusta University, Augusta, 
      GA; Georgia Cancer Center, Augusta, GA.
FAU - Wallis, Christopher J D
AU  - Wallis CJD
AD  - Division of Urology, Department of Surgery, University of Toronto, Toronto, 
      Ontario, Canada; Department of Urologic Surgery, Vanderbilt University Medical 
      Center, Nashville, TN. Electronic address: wallis.cjd@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
PT  - Systematic Review
DEP - 20200306
PL  - United States
TA  - Clin Genitourin Cancer
JT  - Clinical genitourinary cancer
JID - 101260955
RN  - 0 (Androgen Antagonists)
RN  - 0 (Receptors, Androgen)
SB  - IM
MH  - Androgen Antagonists/therapeutic use
MH  - Bayes Theorem
MH  - Humans
MH  - Male
MH  - Network Meta-Analysis
MH  - *Prostatic Neoplasms, Castration-Resistant/drug therapy
MH  - *Receptors, Androgen
OTO - NOTNLM
OT  - Drug-related side effects and adverse reactions
OT  - Nonsteroidal anti-androgens
OT  - Prostatic neoplasms
OT  - Survival
EDAT- 2020/04/13 06:00
MHDA- 2021/08/19 06:00
CRDT- 2020/04/13 06:00
PHST- 2019/12/03 00:00 [received]
PHST- 2020/01/27 00:00 [revised]
PHST- 2020/02/02 00:00 [accepted]
PHST- 2020/04/13 06:00 [pubmed]
PHST- 2021/08/19 06:00 [medline]
PHST- 2020/04/13 06:00 [entrez]
AID - S1558-7673(20)30039-2 [pii]
AID - 10.1016/j.clgc.2020.02.005 [doi]
PST - ppublish
SO  - Clin Genitourin Cancer. 2020 Oct;18(5):343-350. doi: 10.1016/j.clgc.2020.02.005. 
      Epub 2020 Mar 6.