PMID- 36843606
OWN - NLM
STAT- MEDLINE
DCOM- 20230228
LR  - 20230324
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 14
DP  - 2023
TI  - The efficacy and adverse events of conventional and second-generation androgen 
      receptor inhibitors for castration-resistant prostate cancer: A network 
      meta-analysis.
PG  - 1131033
LID - 10.3389/fendo.2023.1131033 [doi]
LID - 1131033
AB  - BACKGROUND: Second-generation androgen receptor inhibitors (ARIs) have been 
      developed and approved for treating castration-resistant prostate cancer (CRPC). 
      There is a lack of direct comparison of the therapeutic effects and adverse 
      events between the conventional ARI (bicalutamide) and three second-generation 
      ARIs (enzalutamide, apalutamide and darolutamide). METHODS: Our network 
      meta-analysis evaluated therapeutic effects and adverse events of the 
      conventional ARI (bicalutamide) and the second-generation ARIs in treating CRPC. 
      We systematically searched the Pubmed, Cochrane library and Embase databases for 
      studies published until October 2022 and only randomized clinical trials (RCTs) 
      were included. The progression-free survival, prostate-specific antigen (PSA) 
      progression-free survival, overall survival (PFS/PSA-PFS/OS), PSA response rate 
      and relative adverse events (AEs) of CRPC patients were collected and 
      synthesized. We then performed subgroup analysis. The non-metastatic and 
      metastatic CRPC (nm/mCRPC) observations were analyzed separately. Data analyses 
      were performed using R software (4.2.1) based on Bayesian framework. RESULTS: 
      6,993 subjects from seven eligible RCTs were analyzed. Enzalutamide, apalutamide 
      and darolutamide were more effective than bicalutamide in treating CRPC, and the 
      performance of darolutamide was slightly worse than the other two 
      second-generation ARIs. Similar adverse events rate were observed among the 
      second-generation ARIs and bicalutamide. Apalutamide showed a slightly higher 
      rate of Grade 3+ AEs, percentages of AE-related drug withdrawals and AE-related 
      mortality. Patients receiving enzalutamide had significantly higher rate of 
      hypertension and fatigue. In subgroup analysis, enzalutamide showed better 
      therapeutic effects compared with bicalutamide in both nmCRPC and mCRPC groups. 
      In nmCRPC group, enzalutamide and apalutamide had more benefits on PFS and 
      PSA-PFS compared with darolutamide. We displayed the probability ranking map of 
      PFS, PSA-PFS, OS, time to cytotoxic chemotherapy, PSA response rate and relative 
      AE outcomes. CONCLUSION: The current network meta-analysis indicated that the 
      second-generation ARIs were superior to the conventional ARI, bicalutamide. The 
      three second-generation ARIs showed incomplete equivalence on CRPC treatment. The 
      darolutamide was slightly less effective compared with enzalutamide and 
      apalutamide. The adverse events of apalutamide were worse than the others, but no 
      statistical significance was observed among these vital AEs. All ARIs were 
      generally well-tolerated. These results may provide reference to clinical 
      decision and further direct comparison trials. SYSTEMATIC REVIEW REGISTRATION: 
      https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022370842.
CI  - Copyright (c) 2023 Zhang, Zhang, Wang and Bi.
FAU - Zhang, Xianlu
AU  - Zhang X
AD  - Department of Urology Surgery, The First Affiliation Hospital of China Medical 
      University, Shenyang, China.
FAU - Zhang, Gejun
AU  - Zhang G
AD  - Department of Urology Surgery, The First Affiliation Hospital of China Medical 
      University, Shenyang, China.
FAU - Wang, Jianfeng
AU  - Wang J
AD  - Department of Urology Surgery, The First Affiliation Hospital of China Medical 
      University, Shenyang, China.
FAU - Bi, Jianbin
AU  - Bi J
AD  - Department of Urology Surgery, The First Affiliation Hospital of China Medical 
      University, Shenyang, China.
LA  - eng
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20230210
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - A0Z3NAU9DP (bicalutamide)
RN  - 93T0T9GKNU (enzalutamide)
RN  - 0 (Receptors, Androgen)
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  - Receptors, Androgen
MH  - Prostate-Specific Antigen/therapeutic use
MH  - Network Meta-Analysis
MH  - Treatment Outcome
MH  - Androgen Receptor Antagonists/adverse effects
PMC - PMC9950258
OTO - NOTNLM
OT  - apalutamide
OT  - bicalutamide
OT  - castration-resistant prostate cancer
OT  - darolutamide
OT  - enzalutamide
OT  - network meta-analysis
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- 2023/02/28 06:00
MHDA- 2023/03/03 06:00
PMCR- 2023/01/01
CRDT- 2023/02/27 03:47
PHST- 2022/12/24 00:00 [received]
PHST- 2023/01/30 00:00 [accepted]
PHST- 2023/02/27 03:47 [entrez]
PHST- 2023/02/28 06:00 [pubmed]
PHST- 2023/03/03 06:00 [medline]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2023.1131033 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2023 Feb 10;14:1131033. doi: 
      10.3389/fendo.2023.1131033. eCollection 2023.