PMID- 34920959
OWN - NLM
STAT- MEDLINE
DCOM- 20220412
LR  - 20220601
IS  - 1938-0682 (Electronic)
IS  - 1558-7673 (Linking)
VI  - 20
IP  - 2
DP  - 2022 Apr
TI  - Impact of New Systemic Therapies in Overall Survival in Non-Metastatic Castration 
      Resistant Prostate Cancer: Systematic Review and Meta-Analysis.
PG  - 197.e1-197.e10
LID - S1558-7673(21)00219-6 [pii]
LID - 10.1016/j.clgc.2021.11.008 [doi]
AB  - There was a high medical need for patients with non-metastatic 
      castration-resistant prostate cancer (nmCRPC) when several next-generation 
      anti-androgens (apalutamide, enzalutamide, and darolutamide) demonstrated 
      clinically relevant delays in metastasis onset. However, to date, few 
      publications have assessed the pooled effect of these treatments on overall 
      survival (OS). We performed a systematic review and meta-analysis of all 
      randomized, placebo-controlled studies investigating a systemic treatment in 
      nmCRPC. Publications were identified by searching several databases on April 7, 
      2021. The primary objective of this analysis was to determine the OS benefit. 
      Secondary outcomes included the relative risk (RR) of adverse events (AEs) and 
      grade 3-4 AEs. A sensitivity analysis with simulated data was also conducted to 
      examine the influence of the study designs on the results. Three randomized 
      controlled studies (SPARTAN, PROSPER, ARAMIS) met our inclusion criteria. Pooled 
      meta-analyses showed a significant benefit in OS with the active agents versus 
      placebo (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.65-0.83), as well 
      as increased risk of any grade (RR 1.09, 95% CI 1.01-1.17) and grade 3-4 AEs (RR 
      1.50, 95% CI 1.23-1.83). The sensitivity analysis with SPARTAN-like simulated 
      populations demonstrated that when using ARAMIS statistical design, OS would be 
      statistically significant in 98.1% of the cases, at a shorter follow-up and with 
      lower number of events. First-line treatment of nmCRPC patients with 
      anti-androgens increased OS with an acceptable safety profile. In light of the 
      different study designs and follow-up, results should be interpreted separately.
CI  - Copyright (c) 2021. Published by Elsevier Inc.
FAU - Rodriguez-Vida, Alejo
AU  - Rodriguez-Vida A
AD  - Medical Oncology Department, Hospital del Mar, IMIM Research Institute, 
      Barcelona, Spain. Electronic address: arodriguezvida@hospitaldelmar.cat.
FAU - Rodriguez-Alonso, Andres
AU  - Rodriguez-Alonso A
AD  - Urology Department, Complexo Universitario de Ferrol, Coruna, Spain.
FAU - Useros-Rodriguez, Eduardo
AU  - Useros-Rodriguez E
AD  - Urology Department, Infanta Elena University Hospital, Madrid, Spain.
FAU - Lopez-Campos, Fernando
AU  - Lopez-Campos F
AD  - Radiation Oncology Department. Ramon y Cajal University Hospital, Madrid, Spain.
FAU - Amor-Carro, Oscar
AU  - Amor-Carro O
AD  - Medical Affairs Department, Janssen, Madrid, Spain.
FAU - Arribas-Ruiz, Alberto
AU  - Arribas-Ruiz A
AD  - Market Access, Janssen, Madrid, Spain.
FAU - Martinez-Torres, Javier
AU  - Martinez-Torres J
AD  - Applied Mathematics Department, University of Vigo, Vigo, Pontevedra, Spain.
FAU - Roca-Pardinas, Javier
AU  - Roca-Pardinas J
AD  - Statistics and Operational Research Department, University of Vigo, Vigo, 
      Pontevedra, Spain.
FAU - Quesada-Garcia, Alba
AU  - Quesada-Garcia A
AD  - Urology Department, Jerez University Hospital, Cadiz, Spain.
FAU - Munoz-Del-Toro, Jacobo R
AU  - Munoz-Del-Toro JR
AD  - Medical Affairs Department, Janssen, Madrid, Spain.
FAU - Juarez-Soto, Alvaro
AU  - Juarez-Soto A
AD  - Urology Department, Jerez University Hospital, Cadiz, Spain.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PT  - Systematic Review
DEP - 20211121
PL  - United States
TA  - Clin Genitourin Cancer
JT  - Clinical genitourinary cancer
JID - 101260955
RN  - 0 (Androgen Antagonists)
RN  - 0 (Androgen Receptor Antagonists)
SB  - IM
MH  - Androgen Antagonists/therapeutic use
MH  - Androgen Receptor Antagonists/therapeutic use
MH  - Humans
MH  - Immunotherapy
MH  - Male
MH  - Proportional Hazards Models
MH  - *Prostatic Neoplasms, Castration-Resistant/pathology
OTO - NOTNLM
OT  - Apalutamide
OT  - Darolutamide
OT  - Enzalutamide
OT  - Next-generation anti-androgens
OT  - Survival analysis
EDAT- 2021/12/19 06:00
MHDA- 2022/04/13 06:00
CRDT- 2021/12/18 05:31
PHST- 2021/09/02 00:00 [received]
PHST- 2021/11/12 00:00 [revised]
PHST- 2021/11/13 00:00 [accepted]
PHST- 2021/12/19 06:00 [pubmed]
PHST- 2022/04/13 06:00 [medline]
PHST- 2021/12/18 05:31 [entrez]
AID - S1558-7673(21)00219-6 [pii]
AID - 10.1016/j.clgc.2021.11.008 [doi]
PST - ppublish
SO  - Clin Genitourin Cancer. 2022 Apr;20(2):197.e1-197.e10. doi: 
      10.1016/j.clgc.2021.11.008. Epub 2021 Nov 21.