PMID- 36682938
OWN - NLM
STAT- MEDLINE
DCOM- 20230619
LR  - 20240111
IS  - 2588-9311 (Electronic)
IS  - 2588-9311 (Linking)
VI  - 6
IP  - 3
DP  - 2023 Jun
TI  - Adverse Events and Androgen Receptor Signaling Inhibitors in the Treatment of 
      Prostate Cancer: A Systematic Review and Multivariate Network Meta-analysis.
PG  - 237-250
LID - S2588-9311(23)00001-9 [pii]
LID - 10.1016/j.euo.2023.01.001 [doi]
AB  - CONTEXT: Androgen receptor signaling inhibitor (ARSi) agents are emerging as 
      standard treatments for prostate cancer across the disease spectrum, but much 
      remains unknown regarding how their side-effect profiles compare. OBJECTIVE: To 
      systematically evaluate the literature regarding adverse events (AEs) between the 
      ARSi drugs abiraterone, apalutamide, darolutamide, and enzalutamide in the 
      treatment of metastatic castration-resistant prostate cancer (mCRPC), 
      nonmetastatic CRPC (nmCRPC), and metastatic castration-sensitive prostate cancer 
      (mCSPC). EVIDENCE ACQUISITION: PubMed, Web of Science, and Embase were queried 
      for double-blind, randomized controlled trials (RCTs) of ARSi therapy up to 
      September 2022 according to the Preferred Reporting Items for Systematic Review 
      and Meta-Analysis (PRISMA) statement. Two teams reviewed titles and abstracts, 
      and 14 RCTs were included for analysis. EVIDENCE SYNTHESIS: Forest plots were 
      used to summarize risk ratios for the most common AEs. According to surface under 
      the cumulative ranking curve (SUCRA) values, enzalutamide was ranked as the most 
      toxic treatment regarding hypertension outcomes (SUCRA 0%, most likely to be the 
      bottom-ranked treatment) in both mCRPC and nmCRPC (SUCRA 0%). Enzalutamide was 
      also ranked as the most toxic regarding headache across all prostate cancer 
      entities (SUCRA 0%, for mCRPC, 1% for nmCRPC, and 3% for mCSPC). CONCLUSIONS: Our 
      findings suggest that the ARSi side-effect profiles do not significantly differ, 
      except that enzalutamide was ranked the most toxic regarding hypertension in 
      mCRPC and nmCRPC, and the most toxic regarding headache across all prostate 
      cancer settings. These results highlight the importance of close blood-pressure 
      monitoring for enzalutamide, and future research should explore possible 
      connections between cardiovascular and neurological risk with ARSi therapy. In 
      addition, these comparisons rely on the validity of cross-trial comparisons. 
      PATIENT SUMMARY: We reviewed the side-effect profiles of second-generation 
      antiandrogen drugs for the treatment of prostate cancer. Side effects were 
      similar, apart from higher risk of high blood pressure and headache risk with 
      enzalutamide.
CI  - Copyright (c) 2023 European Association of Urology. Published by Elsevier B.V. All 
      rights reserved.
FAU - Cao, Brent
AU  - Cao B
AD  - Department of Urology, University of Illinois College of Medicine, Chicago, IL, 
      USA. Electronic address: bcao9@uic.edu.
FAU - Kim, Melissa
AU  - Kim M
AD  - Department of Urology, University of Illinois College of Medicine, Chicago, IL, 
      USA.
FAU - Reizine, Natalie M
AU  - Reizine NM
AD  - Department of Medicine, Division of Hematology and Oncology, University of 
      Illinois College of Medicine, Chicago, IL, USA.
FAU - Moreira, Daniel M
AU  - Moreira DM
AD  - Department of Urology, University of Illinois College of Medicine, Chicago, IL, 
      USA.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
PT  - Systematic Review
DEP - 20230120
PL  - Netherlands
TA  - Eur Urol Oncol
JT  - European urology oncology
JID - 101724904
RN  - 93T0T9GKNU (enzalutamide)
RN  - 0 (Receptors, Androgen)
RN  - 0 (Androgen Receptor Antagonists)
SB  - IM
MH  - Male
MH  - Humans
MH  - *Prostatic Neoplasms, Castration-Resistant/pathology
MH  - Receptors, Androgen
MH  - Network Meta-Analysis
MH  - Androgen Receptor Antagonists/adverse effects
MH  - Headache/drug therapy
MH  - Randomized Controlled Trials as Topic
OTO - NOTNLM
OT  - Adverse events
OT  - Androgen receptor signaling inhibitor
OT  - Multivariate network meta-analysis
OT  - Prostate cancer
EDAT- 2023/01/23 06:00
MHDA- 2023/06/19 13:09
CRDT- 2023/01/22 22:02
PHST- 2022/08/06 00:00 [received]
PHST- 2022/12/04 00:00 [revised]
PHST- 2023/01/02 00:00 [accepted]
PHST- 2023/06/19 13:09 [medline]
PHST- 2023/01/23 06:00 [pubmed]
PHST- 2023/01/22 22:02 [entrez]
AID - S2588-9311(23)00001-9 [pii]
AID - 10.1016/j.euo.2023.01.001 [doi]
PST - ppublish
SO  - Eur Urol Oncol. 2023 Jun;6(3):237-250. doi: 10.1016/j.euo.2023.01.001. Epub 2023 
      Jan 20.