PMID- 32924096
OWN - NLM
STAT- MEDLINE
DCOM- 20201204
LR  - 20230216
IS  - 1437-7772 (Electronic)
IS  - 1341-9625 (Print)
IS  - 1341-9625 (Linking)
VI  - 25
IP  - 11
DP  - 2020 Nov
TI  - Apalutamide, enzalutamide, and darolutamide for non-metastatic 
      castration-resistant prostate cancer: a systematic review and network 
      meta-analysis.
PG  - 1892-1900
LID - 10.1007/s10147-020-01777-9 [doi]
AB  - Management of non-metastatic castration-resistant prostate cancer (nmCRPC) has 
      undergone a paradigm shift with next-generation androgen receptor inhibitors. 
      However, direct comparative data are not available to inform treatment decisions 
      and/or guideline recommendations. Therefore, we performed network meta-analysis 
      to indirectly compare the efficacy and safety of currently available treatments. 
      Multiple databases were searched for articles published before June 2020. Studies 
      that compared overall and/or metastasis-free and/or prostate-specific antigen 
      (PSA) progression-free survival (OS/MFS/PSA-PFS) and/or adverse events (AEs) in 
      nmCRPC patients were considered eligible. Three studies (n = 4117) met our 
      eligibility criteria. Formal network meta-analyses were conducted. For MFS, 
      apalutamide, darolutamide, and enzalutamide were significantly more effective 
      than placebo, and apalutamide emerged as the best option (P score: 0.8809). 
      Apalutamide [hazard ratio (HR): 0.85, 95% credible interval (CrI): 0.77-0.94] and 
      enzalutamide (HR: 0.86, 95% CrI: 0.78-0.95) were both significantly more 
      effective than darolutamide. For PSA-PFS, all three agents were statistically 
      superior to placebo, and apalutamide emerged as the likely preferred option (P 
      score: 1.000). Apalutamide (HR: 0.71, 95% CrI: 0.69-0.74) and enzalutamide (HR: 
      0.76, 95% CrI: 0.74-0.79) were both significantly more effective than 
      darolutamide. For AEs (including all AEs, grade 3 or grade 4 AEs, grade 5 AEs, 
      and discontinuation rates), darolutamide was the likely best option. Apalutamide 
      and enzalutamide appear to be more efficacious agents for therapy of nmCRPC, 
      while darolutamide appears to have the most favorable tolerability profile. These 
      findings may facilitate individualized treatment strategies and inform future 
      direct comparative trials.
FAU - Mori, Keiichiro
AU  - Mori K
AUID- ORCID: 0000-0002-6147-6569
AD  - Department of Urology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
AD  - Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
FAU - Mostafaei, Hadi
AU  - Mostafaei H
AD  - Department of Urology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
AD  - Research Center for Evidence Based Medicine, Tabriz University of Medical 
      Sciences, Tabriz, Iran.
FAU - Pradere, Benjamin
AU  - Pradere B
AD  - Department of Urology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
AD  - Deaprtment of Urology, PRES Centre Val de Loire, CHRU Tours, France, Universite 
      Francois Rabelais de Tours, Tours, France.
FAU - Motlagh, Reza Sari
AU  - Motlagh RS
AD  - Department of Urology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
FAU - Quhal, Fahad
AU  - Quhal F
AD  - Department of Urology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
AD  - Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia.
FAU - Laukhtina, Ekaterina
AU  - Laukhtina E
AD  - Department of Urology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
AD  - Institute for Urology and Reproductive Health, Sechenov University, Moscow, 
      Russia.
FAU - Schuettfort, Victor M
AU  - Schuettfort VM
AD  - Department of Urology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
AD  - Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Abufaraj, Mohammad
AU  - Abufaraj M
AD  - Department of Urology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria.
AD  - Division of Urology, Department of Special Surgery, The University of Jordan, 
      Amman, Jordan.
FAU - Karakiewicz, Pierre I
AU  - Karakiewicz PI
AD  - Cancer Prognostics and Health Outcomes Unit, University of Montreal Health 
      Centre, Montreal, Canada.
FAU - Kimura, Takahiro
AU  - Kimura T
AD  - Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
FAU - Egawa, Shin
AU  - Egawa S
AD  - Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
FAU - Shariat, Shahrokh F
AU  - Shariat SF
AD  - Department of Urology, Medical University of Vienna, Wahringer Gurtel 18-20, 
      1090, Vienna, Austria. shahrokh.shariat@meduniwien.ac.at.
AD  - Institute for Urology and Reproductive Health, Sechenov University, Moscow, 
      Russia. shahrokh.shariat@meduniwien.ac.at.
AD  - Division of Urology, Department of Special Surgery, The University of Jordan, 
      Amman, Jordan. shahrokh.shariat@meduniwien.ac.at.
AD  - Department of Urology, Weill Cornell Medical College, New York, NY, USA. 
      shahrokh.shariat@meduniwien.ac.at.
AD  - Department of Urology, University of Texas Southwestern, Dallas, TX, USA. 
      shahrokh.shariat@meduniwien.ac.at.
AD  - Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria. 
      shahrokh.shariat@meduniwien.ac.at.
AD  - Department of Urology, Second Faculty of Medicine, Charles University, Prague, 
      Czech Republic. shahrokh.shariat@meduniwien.ac.at.
AD  - European Association of Urology Research Foundation, Arnhem, Netherlands. 
      shahrokh.shariat@meduniwien.ac.at.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20200914
PL  - Japan
TA  - Int J Clin Oncol
JT  - International journal of clinical oncology
JID - 9616295
RN  - 0 (Androgen Receptor Antagonists)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzamides)
RN  - 0 (Nitriles)
RN  - 0 (Pyrazoles)
RN  - 0 (Thiohydantoins)
RN  - 0 (apalutamide)
RN  - 0 (darolutamide)
RN  - 2010-15-3 (Phenylthiohydantoin)
RN  - 93T0T9GKNU (enzalutamide)
RN  - EC 3.4.21.- (KLK3 protein, human)
RN  - EC 3.4.21.- (Kallikreins)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
SB  - IM
MH  - Androgen Receptor Antagonists/*therapeutic use
MH  - Antineoplastic Agents/therapeutic use
MH  - Benzamides
MH  - Humans
MH  - Kallikreins/metabolism
MH  - Male
MH  - Network Meta-Analysis
MH  - Nitriles
MH  - Phenylthiohydantoin/analogs & derivatives/therapeutic use
MH  - Progression-Free Survival
MH  - Proportional Hazards Models
MH  - Prostate-Specific Antigen/metabolism
MH  - Prostatic Neoplasms, Castration-Resistant/*drug therapy/mortality/pathology
MH  - Pyrazoles/therapeutic use
MH  - Thiohydantoins/therapeutic use
MH  - Treatment Outcome
PMC - PMC7572325
OTO - NOTNLM
OT  - Apalutamide
OT  - Darolutamide
OT  - Enzalutamide
OT  - Network meta-analysis
OT  - Non-metastatic castration-resistant prostate cancer
COIS- None of the authors have conflicts of interest to disclose.
EDAT- 2020/09/15 06:00
MHDA- 2020/12/15 06:00
PMCR- 2020/09/14
CRDT- 2020/09/14 05:58
PHST- 2020/06/01 00:00 [received]
PHST- 2020/08/16 00:00 [accepted]
PHST- 2020/09/15 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/09/14 05:58 [entrez]
PHST- 2020/09/14 00:00 [pmc-release]
AID - 10.1007/s10147-020-01777-9 [pii]
AID - 1777 [pii]
AID - 10.1007/s10147-020-01777-9 [doi]
PST - ppublish
SO  - Int J Clin Oncol. 2020 Nov;25(11):1892-1900. doi: 10.1007/s10147-020-01777-9. 
      Epub 2020 Sep 14.