Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer.
Adenocarcinoma
/ drug therapy
Aged
Androgen Antagonists
/ therapeutic use
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Benzamides
Double-Blind Method
Humans
Kallikreins
/ blood
Kaplan-Meier Estimate
Male
Middle Aged
Nitriles
Phenylthiohydantoin
/ adverse effects
Placebos
Prostate-Specific Antigen
/ blood
Prostatic Neoplasms, Castration-Resistant
/ drug therapy
Survival Analysis
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
04 06 2020
04 06 2020
Historique:
pubmed:
30
5
2020
medline:
12
6
2020
entrez:
30
5
2020
Statut:
ppublish
Résumé
Preliminary trial results showed that enzalutamide significantly improved metastasis-free survival among men who had nonmetastatic, castration-resistant prostate cancer and rapidly increasing prostate-specific antigen (PSA) levels while taking androgen-deprivation therapy. Results from the final analysis of overall survival have not yet been reported. In this double-blind, phase 3 trial, men with nonmetastatic, castration-resistant prostate cancer (defined on the basis of conventional imaging and a PSA doubling time of ≤10 months) who were continuing to receive androgen-deprivation therapy were randomly assigned (in a 2:1 ratio) to receive enzalutamide at a dose of 160 mg or placebo once daily. Overall survival was assessed with a group sequential testing procedure and an O'Brien-Fleming-type alpha-spending function. As of October 15, 2019, a total of 288 of 933 patients (31%) in the enzalutamide group and 178 of 468 (38%) in the placebo group had died. Median overall survival was 67.0 months (95% confidence interval [CI], 64.0 to not reached) in the enzalutamide group and 56.3 months (95% CI, 54.4 to 63.0) in the placebo group (hazard ratio for death, 0.73; 95% CI, 0.61 to 0.89; P = 0.001). The exposure-adjusted rate of adverse events of grade 3 or higher was 17 per 100 patient-years in the enzalutamide group and 20 per 100 patient-years in the placebo group. Adverse events in the enzalutamide group were consistent with those previously reported for enzalutamide; the most frequently reported events were fatigue and musculoskeletal events. Enzalutamide plus androgen-deprivation therapy resulted in longer median overall survival than placebo plus androgen-deprivation therapy among men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising PSA level. The risk of death associated with enzalutamide was 27% lower than with placebo. Adverse events were consistent with the established safety profile of enzalutamide. (Funded by Pfizer and Astellas Pharma; PROSPER ClinicalTrials.gov number, NCT02003924.).
Sections du résumé
BACKGROUND
Preliminary trial results showed that enzalutamide significantly improved metastasis-free survival among men who had nonmetastatic, castration-resistant prostate cancer and rapidly increasing prostate-specific antigen (PSA) levels while taking androgen-deprivation therapy. Results from the final analysis of overall survival have not yet been reported.
METHODS
In this double-blind, phase 3 trial, men with nonmetastatic, castration-resistant prostate cancer (defined on the basis of conventional imaging and a PSA doubling time of ≤10 months) who were continuing to receive androgen-deprivation therapy were randomly assigned (in a 2:1 ratio) to receive enzalutamide at a dose of 160 mg or placebo once daily. Overall survival was assessed with a group sequential testing procedure and an O'Brien-Fleming-type alpha-spending function.
RESULTS
As of October 15, 2019, a total of 288 of 933 patients (31%) in the enzalutamide group and 178 of 468 (38%) in the placebo group had died. Median overall survival was 67.0 months (95% confidence interval [CI], 64.0 to not reached) in the enzalutamide group and 56.3 months (95% CI, 54.4 to 63.0) in the placebo group (hazard ratio for death, 0.73; 95% CI, 0.61 to 0.89; P = 0.001). The exposure-adjusted rate of adverse events of grade 3 or higher was 17 per 100 patient-years in the enzalutamide group and 20 per 100 patient-years in the placebo group. Adverse events in the enzalutamide group were consistent with those previously reported for enzalutamide; the most frequently reported events were fatigue and musculoskeletal events.
CONCLUSIONS
Enzalutamide plus androgen-deprivation therapy resulted in longer median overall survival than placebo plus androgen-deprivation therapy among men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising PSA level. The risk of death associated with enzalutamide was 27% lower than with placebo. Adverse events were consistent with the established safety profile of enzalutamide. (Funded by Pfizer and Astellas Pharma; PROSPER ClinicalTrials.gov number, NCT02003924.).
Identifiants
pubmed: 32469184
doi: 10.1056/NEJMoa2003892
doi:
Substances chimiques
Androgen Antagonists
0
Benzamides
0
Nitriles
0
Placebos
0
Phenylthiohydantoin
2010-15-3
enzalutamide
93T0T9GKNU
KLK3 protein, human
EC 3.4.21.-
Kallikreins
EC 3.4.21.-
Prostate-Specific Antigen
EC 3.4.21.77
Banques de données
ClinicalTrials.gov
['NCT02003924']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2197-2206Investigateurs
S Carraro
(S)
O Damia
(O)
L Fein
(L)
L F Montes de Oca
(LF)
M S Varela
(MS)
E Abdi
(E)
S Begbie
(S)
T Bonaventura
(T)
A Boyce
(A)
P Craft
(P)
I Davis
(I)
A Guminski
(A)
H Gurney
(H)
A Hill
(A)
G Marx
(G)
E McCaffrey
(E)
F Parnis
(F)
D Pook
(D)
J Shapiro
(J)
M Slancar
(M)
M Stockler
(M)
G Toner
(G)
C Underhill
(C)
P Vasey
(P)
A Weickhardt
(A)
S Wong
(S)
H Woo
(H)
M Krainer
(M)
W Loidl
(W)
F Ameye
(F)
S Joniau
(S)
T Roumeguere
(T)
D Waltregny
(D)
P Werbrouck
(P)
C Cairoli
(C)
A L Coradazzi
(AL)
D Cubero
(D)
R Damião
(R)
E R De Mattos
(ER)
F A M de Oliveira
(FAM)
U Ferreira
(U)
F Franke
(F)
D Herchenhorn
(D)
A Lessa
(A)
P Liedke
(P)
E Rhoden
(E)
N S Lazaretti
(NS)
O Smaletz
(O)
L Aaron
(L)
A Aprikian
(A)
D Drachenberg
(D)
R B Egerdie
(RB)
N Fleshner
(N)
M Gleave
(M)
L Klotz
(L)
M Kolinsky
(M)
L Lacombe
(L)
R Rendon
(R)
D Ruether
(D)
F Saad
(F)
B Shayegan
(B)
E Winquist
(E)
J Zadra
(J)
C Caglevic
(C)
P F Gonzalez Mella
(PF)
M R Mahave Caceres
(MR)
E Yanez
(E)
C Du
(C)
H Guo
(H)
S Hou
(S)
Q Hu
(Q)
L Hua
(L)
H Jiang
(H)
J Jin
(J)
H Li
(H)
T Liu
(T)
H Luo
(H)
L Ma
(L)
J Qi
(J)
Y Sun
(Y)
J Wang
(J)
Z Weng
(Z)
S Xia
(S)
Y Xu
(Y)
D Ye
(D)
J Yuan
(J)
Q Zou
(Q)
L Andersen
(L)
M Borre
(M)
S Carlsson
(S)
P Iversen
(P)
B Norby
(B)
M H Poulsen
(MH)
P Rathenborg
(P)
T Joensuu
(T)
T Joutsi
(T)
A Kaipia
(A)
H Ronkainen
(H)
K Taari
(K)
T Tammela
(T)
D Azria
(D)
M Baciuchka
(M)
P Barthelemy
(P)
P Beuzeboc
(P)
E Bompas
(E)
L Cartier
(L)
M Colombel
(M)
R Delva
(R)
K Fizazi
(K)
A Flechon
(A)
M Gross-Goupil
(M)
S Ladoire
(S)
L Mourey
(L)
S Oudard
(S)
F Ricci
(F)
F Schlürmann-Constans
(F)
S Tartas
(S)
Y Tazi
(Y)
J-M Tourani
(JM)
A Villers
(A)
E Voog
(E)
S Feyerabend
(S)
K Miller
(K)
P Nuhn
(P)
M Ritter
(M)
P Stroelin
(P)
T Steuber
(T)
C von Klot
(C)
M Wirth
(M)
A Bamias
(A)
E Efstathiou
(E)
A Farmakis
(A)
N Ferakis
(N)
E Ioannidis
(E)
H Kalofonos
(H)
V Tzortzis
(V)
K C Lee
(KC)
C F Ng
(CF)
J H-L Tsu
(JH)
U Basso
(U)
O Caffo
(O)
F Calabrò
(F)
F Carrozza
(F)
U De Giorgi
(U)
R Passalacqua
(R)
G Procopio
(G)
R Sabbatini
(R)
G V Scagliotti
(GV)
C N Sternberg
(CN)
A Alip
(A)
F Ismail
(F)
G C Teh
(GC)
M De Wildt
(M)
I deJong
(I)
C van de Beek
(C)
J van den Bosch
(J)
J G H van Roermund
(JGH)
P Fong
(P)
B Hindson
(B)
M Holmes
(M)
N Nedev
(N)
Z Jablonska
(Z)
J Jassem
(J)
K Madziarska
(K)
M Obarzanowski
(M)
J Olubiec
(J)
Y-D Choi
(YD)
B H Chung
(BH)
H Jung
(H)
C-S Kim
(CS)
C Kwak
(C)
D-D Kwon
(DD)
H-M Lee
(HM)
B Alekseev
(B)
S A-Shukri
(S)
A Izmailov
(A)
V Matveev
(V)
N Bojanic
(N)
B Cvetkovic
(B)
Z Filipovic
(Z)
D Kojic
(D)
E Chiong
(E)
R Kanesvaran
(R)
V Balaz
(V)
P Dubinsky
(P)
F Goncalves
(F)
J Kliment
(J)
J Marko
(J)
J Mikulas
(J)
I Mincik
(I)
A Alcaraz
(A)
J A Arranz Arija
(JA)
M Domenech
(M)
E Gallardo Díaz
(E)
A Gomez Caamaño
(A)
N Lainez Milagro
(N)
A Rodríguez Antolín
(A)
J I Rodriguez Gomez
(JI)
N Sala Gonzalez
(N)
A Zapatero
(A)
O Andrén
(O)
A Bjartell
(A)
J-E Damber
(JE)
B Ljungberg
(B)
U Norming
(U)
C Nyman
(C)
M Olsson
(M)
H-Y Chang
(HY)
C-S Chen
(CS)
P-H Chiang
(PH)
H-J Chung
(HJ)
S-P Huang
(SP)
Y-C Lin
(YC)
Y-C Ou
(YC)
Y-S Pu
(YS)
K-H Shen
(KH)
J-C Wang
(JC)
C-T Wu
(CT)
H-C Wu
(HC)
T Wu
(T)
C-K Yang
(CK)
J Opanuraks
(J)
C Pripatnanont
(C)
S Sriplakich
(S)
N Wongwattanasatien
(N)
T Degirimenci
(T)
H Ozen
(H)
M Ozguroglu
(M)
Z Tansug
(Z)
I Antonyan
(I)
Y Hotko
(Y)
P Ivashchenko
(P)
O Lyulko
(O)
V Stus
(V)
G Attard
(G)
A Bahl
(A)
J S De Bono
(JS)
P A Elliot
(PA)
S Jain
(S)
N James
(N)
D Mazhar
(D)
H Payne
(H)
I D Pedley
(ID)
A Protheroe
(A)
B Adesunloye
(B)
W Berry
(W)
C Canfield
(C)
B Cowan
(B)
C Dunshee
(C)
L Gervasi
(L)
R Given
(R)
I Grunberger
(I)
M Hussain
(M)
F Joudi
(F)
V L Kakani
(VL)
K Kernen
(K)
B Mehlhaff
(B)
S Nguyen
(S)
L Nordquist
(L)
A Pantuck
(A)
D Penson
(D)
D Petrylak
(D)
S Polsky
(S)
D Saltzstein
(D)
N Shore
(N)
P Sieber
(P)
J Singh
(J)
D C Smith
(DC)
R Suh
(R)
J Uberoi
(J)
E Uchio
(E)
R Waterhouse
(R)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 Massachusetts Medical Society.