PMID- 34722276
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220427
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 11
DP  - 2021
TI  - Novel Androgen Receptor Inhibitors in Non-Metastatic, Castration-Resistant 
      Prostate Cancer: A Systematic Review and Network Meta-Analysis.
PG  - 733202
LID - 10.3389/fonc.2021.733202 [doi]
LID - 733202
AB  - INTRODUCTION: Enzalutamide, apalutamide, and darolutamide have all been approved 
      by Food and Drug Administration to treat high-risk non-metastatic 
      castration-resistant prostate cancer (nmCRPC) since 2018 based on interim results 
      of several phase III clinical trials. Final analyses of long-term overall 
      survival (OS) and adverse events (AEs) results of these trials have been 
      successively published recently. To help clinical practice to precisely select 
      optimal treatment for high-risk nmCRPC patients, we performed a network 
      meta-analysis to indirectly compare the final long-term results among 
      these medications. METHODS: PubMed, EMBASE, and Cochrane Libraries were searched 
      for phase III clinical trial that reports OS and AEs results in nmCRPC patients 
      published before January 30, 2021. Primary outcome was OS; secondary outcomes 
      were Time to first chemotherapy, Subsequent antineoplastic therapy rate, and AEs. 
      Firstly, class-level effect was assessed as the second-generation androgen 
      receptor antagonists (SGARAs) were regarded as one whole class compared with 
      placebo through traditional meta-analysis by using Revman 5.4, then a Bayesian 
      network meta-analysis was conducted to give indirect comparison among SGARAs by 
      using R 3.5.3 software. Subgroup analysis of OS was only conducted in the certain 
      subgroups which were available in all included studies. RESULTS: Three eligible 
      studies including 4,104 participants were finally selected. OS was significantly 
      improved by the SGARAs as a class compared with placebo (HR, 0.74; 95% CI, 
      0.66-0.84). Darolutamide had the highest likelihood of providing best OS 
      (p-score=0.802). SGARAs also significantly delayed the first time to chemotherapy 
      (HR, 0.58; 95% CI, 0.50-0.66). Patients who received darolutamide experienced 
      similar toxicity compared with placebo regarding AEs of grade 3 or higher (OR, 
      1.3; 95% CI, 1.0-1.7) and serious AEs (OR, 1.3; 95% CI, 0.99-1.6). When compared 
      with darolutamide, enzalutamide caused significantly higher toxicity in terms of 
      any AEs (OR, 2.3; 95% CI,1.5-3.7) and AEs of grade 3 or higher (OR, 1.6; 95% CI, 
      1.1-2.2), apalutamide caused significantly more AEs of grade 3 or higher (OR, 
      1.9; 95% CI, 1.4-2.7) and serious AEs (OR, 1.9; 95% CI, 1.3-2.8). Subgroup 
      analysis showed that SGARAs as a group significantly improved OS in ECOG=1 
      population, although insignificant results were found in these patients from 
      included studies. CONCLUSIONS: SGARAs combined with ADT significantly improved OS 
      when compared with ADT alone in high-risk nmCRPC patients. Darolutamide may not 
      only provide best OS but also have the most favorable safety profile among the 
      included SGARAs in high-risk nmCRPC patients.
CI  - Copyright (c) 2021 Mulati, Fan, Yu, Zhang and He.
FAU - Mulati, Yelin
AU  - Mulati Y
AD  - Department of Urology, Peking University First Hospital, Beijing, China.
AD  - Institute of Urology, Peking University, Beijing, China.
AD  - National Urological Cancer Center, Beijing, China.
FAU - Fan, Yu
AU  - Fan Y
AD  - Department of Urology, Peking University First Hospital, Beijing, China.
AD  - Institute of Urology, Peking University, Beijing, China.
AD  - National Urological Cancer Center, Beijing, China.
FAU - Yu, Wei
AU  - Yu W
AD  - Department of Urology, Peking University First Hospital, Beijing, China.
AD  - Institute of Urology, Peking University, Beijing, China.
AD  - National Urological Cancer Center, Beijing, China.
FAU - Zhang, Qian
AU  - Zhang Q
AD  - Department of Urology, Peking University First Hospital, Beijing, China.
AD  - Institute of Urology, Peking University, Beijing, China.
AD  - National Urological Cancer Center, Beijing, China.
AD  - Peking University Binhai Hospital, Tianjin, China.
FAU - He, Zhisong
AU  - He Z
AD  - Department of Urology, Peking University First Hospital, Beijing, China.
AD  - Institute of Urology, Peking University, Beijing, China.
AD  - National Urological Cancer Center, Beijing, China.
LA  - eng
PT  - Systematic Review
DEP - 20211015
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC8555656
OTO - NOTNLM
OT  - adverse events
OT  - hormonal therapies
OT  - network meta-analysis
OT  - non-metastatic castration-resistant prostate cancer (nmCRPC)
OT  - overall survival (OS)
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/11/02 06:00
MHDA- 2021/11/02 06:01
PMCR- 2021/01/01
CRDT- 2021/11/01 09:24
PHST- 2021/06/30 00:00 [received]
PHST- 2021/09/23 00:00 [accepted]
PHST- 2021/11/01 09:24 [entrez]
PHST- 2021/11/02 06:00 [pubmed]
PHST- 2021/11/02 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2021.733202 [doi]
PST - epublish
SO  - Front Oncol. 2021 Oct 15;11:733202. doi: 10.3389/fonc.2021.733202. eCollection 
      2021.