PMID- 26578735
OWN - NLM
STAT- MEDLINE
DCOM- 20161111
LR  - 20220309
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 27
IP  - 2
DP  - 2016 Feb
TI  - Efficacy and safety of enzalutamide in patients 75 years or older with 
      chemotherapy-naive metastatic castration-resistant prostate cancer: results from 
      PREVAIL.
PG  - 286-94
LID - 10.1093/annonc/mdv542 [doi]
AB  - BACKGROUND: Prostate cancer disproportionately affects older men. Because age 
      affects treatment decisions, it is important to understand the efficacy and 
      tolerability of therapies for advanced prostate cancer in elderly men. This 
      analysis describes efficacy and safety outcomes in men aged >/=75 years who 
      received enzalutamide, an androgen receptor inhibitor, in the phase III PREVAIL 
      trial. PATIENTS AND METHODS: PREVAIL was a randomised, double-blind, 
      multinational study of oral enzalutamide 160 mg/day (N = 872) versus placebo (N = 
      845) in chemotherapy-naive men with metastatic castration-resistant prostate 
      cancer. Overall survival (OS) and radiographic progression-free survival (rPFS) 
      were coprimary end points. Subgroup analysis of men aged >/=75 years (elderly) and 
      men aged <75 years was pre-specified for the coprimary end points and adverse 
      events (AEs). RESULTS: Among 609 elderly patients (35%) who participated in 
      PREVAIL, median treatment duration was 16.6 and 5.0 months in the enzalutamide 
      and placebo arms, respectively. In the elderly subgroup, OS was greater with 
      enzalutamide than with placebo [32.4 months (95% confidence interval (CI) 
      27.7-not yet reached] versus 25.1 months (95% CI 22.6-28.0); hazard ratio (HR) = 
      0.61 (95% CI 0.47-0.79); P = 0.0001], as was rPFS [not yet reached (95% CI 
      12.3-not yet reached) versus 3.7 months (95% CI 3.6-5.3); HR = 0.17 (95% CI 
      0.12-0.24); P < 0.0001]. Irrespective of treatment assignment, incidence of AEs 
      was similar between the two age groups, except for an overall higher incidence of 
      falls among elderly patients than younger patients [84/609 (13.8%) versus 62/1106 
      (5.6%)] and among elderly patients receiving enzalutamide than those receiving 
      placebo [61/317 (19.2%) versus 23/292 (7.9%)]. CONCLUSIONS: Elderly men benefited 
      from treatment with enzalutamide in terms of OS and rPFS. Enzalutamide was well 
      tolerated in the elderly subgroup and those aged <75 years. Age and enzalutamide 
      treatment were associated with a higher incidence of falls. CLINICAL TRIAL 
      IDENTIFIER: NCT01212991, ClinicalTrials.gov.
CI  - (c) The Author 2015. Published by Oxford University Press on behalf of the European 
      Society for Medical Oncology. All rights reserved. For permissions, please email: 
      journals.permissions@oup.com.
FAU - Graff, J N
AU  - Graff JN
AD  - Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon 
      Health & Science University, Portland Division of Oncology, Portland VA Medical 
      Center, Portland, USA graffj@ohsu.edu.
FAU - Baciarello, G
AU  - Baciarello G
AD  - Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy.
FAU - Armstrong, A J
AU  - Armstrong AJ
AD  - Divisions of Medical Oncology and Urology, Duke University Medical Center and the 
      Duke Cancer Institute, Durham.
FAU - Higano, C S
AU  - Higano CS
AD  - Division of Medical Oncology, University of Washington and Fred Hutchinson Cancer 
      Research Center, Seattle, USA.
FAU - Iversen, P
AU  - Iversen P
AD  - Copenhagen Prostate Cancer Center, Rigshospitalet, University of Copenhagen, 
      Kobenhavn, Denmark.
FAU - Flaig, T W
AU  - Flaig TW
AD  - Department of Medical Oncology, University of Colorado Cancer Center, Aurora.
FAU - Forer, D
AU  - Forer D
AD  - Medivation, Inc., San Francisco, USA.
FAU - Parli, T
AU  - Parli T
AD  - Medivation, Inc., San Francisco, USA.
FAU - Phung, D
AU  - Phung D
AD  - Astellas Pharma Global Development, Inc., Leiden, The Netherlands.
FAU - Tombal, B
AU  - Tombal B
AD  - Department of Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
FAU - Beer, T M
AU  - Beer TM
AD  - Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon 
      Health & Science University, Portland.
FAU - Sternberg, C N
AU  - Sternberg CN
AD  - Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy.
LA  - eng
SI  - ClinicalTrials.gov/NCT01212991
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20151116
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Androgen Receptor Antagonists)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzamides)
RN  - 0 (Nitriles)
RN  - 0 (Placebos)
RN  - 2010-15-3 (Phenylthiohydantoin)
RN  - 93T0T9GKNU (enzalutamide)
SB  - IM
MH  - Accidental Falls/statistics & numerical data
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Androgen Receptor Antagonists/adverse effects/*therapeutic use
MH  - Antineoplastic Agents/adverse effects/*therapeutic use
MH  - Benzamides
MH  - Disease-Free Survival
MH  - Double-Blind Method
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nitriles
MH  - Phenylthiohydantoin/adverse effects/*analogs & derivatives/therapeutic use
MH  - Placebos
MH  - Prostatic Neoplasms, Castration-Resistant/*drug therapy/mortality/pathology
OTO - NOTNLM
OT  - PREVAIL trial
OT  - elderly patients
OT  - enzalutamide
OT  - metastatic castration-resistant prostate cancer
EDAT- 2015/11/19 06:00
MHDA- 2016/11/12 06:00
CRDT- 2015/11/19 06:00
PHST- 2015/08/11 00:00 [received]
PHST- 2015/10/21 00:00 [accepted]
PHST- 2015/11/19 06:00 [entrez]
PHST- 2015/11/19 06:00 [pubmed]
PHST- 2016/11/12 06:00 [medline]
AID - S0923-7534(19)35544-9 [pii]
AID - 10.1093/annonc/mdv542 [doi]
PST - ppublish
SO  - Ann Oncol. 2016 Feb;27(2):286-94. doi: 10.1093/annonc/mdv542. Epub 2015 Nov 16.