Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer.
Adenocarcinoma
/ drug therapy
Aged
Androgen Receptor Antagonists
/ adverse effects
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Benzamides
Bone Neoplasms
/ drug therapy
Digestive System Neoplasms
/ drug therapy
Fatigue
/ chemically induced
Follow-Up Studies
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Nitriles
Phenylthiohydantoin
/ adverse effects
Progression-Free Survival
Prostatic Neoplasms
/ drug therapy
Seizures
/ chemically induced
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:
11 07 2019
11 07 2019
Historique:
pubmed:
4
6
2019
medline:
28
7
2019
entrez:
4
6
2019
Statut:
ppublish
Résumé
Enzalutamide, an androgen-receptor inhibitor, has been associated with improved overall survival in men with castration-resistant prostate cancer. It is not known whether adding enzalutamide to testosterone suppression, with or without early docetaxel, will improve survival in men with metastatic, hormone-sensitive prostate cancer. In this open-label, randomized, phase 3 trial, we assigned patients to receive testosterone suppression plus either open-label enzalutamide or a standard nonsteroidal antiandrogen therapy (standard-care group). The primary end point was overall survival. Secondary end points included progression-free survival as determined by the prostate-specific antigen (PSA) level, clinical progression-free survival, and adverse events. A total of 1125 men underwent randomization; the median follow-up was 34 months. There were 102 deaths in the enzalutamide group and 143 deaths in the standard-care group (hazard ratio, 0.67; 95% confidence interval [CI], 0.52 to 0.86; P = 0.002). Kaplan-Meier estimates of overall survival at 3 years were 80% (based on 94 events) in the enzalutamide group and 72% (based on 130 events) in the standard-care group. Better results with enzalutamide were also seen in PSA progression-free survival (174 and 333 events, respectively; hazard ratio, 0.39; P<0.001) and in clinical progression-free survival (167 and 320 events, respectively; hazard ratio, 0.40; P<0.001). Treatment discontinuation due to adverse events was more frequent in the enzalutamide group than in the standard-care group (33 events and 14 events, respectively). Fatigue was more common in the enzalutamide group; seizures occurred in 7 patients in the enzalutamide group (1%) and in no patients in the standard-care group. Enzalutamide was associated with significantly longer progression-free and overall survival than standard care in men with metastatic, hormone-sensitive prostate cancer receiving testosterone suppression. The enzalutamide group had a higher incidence of seizures and other toxic effects, especially among those treated with early docetaxel. (Funded by Astellas Scientific and Medical Affairs and others; ENZAMET (ANZUP 1304) ANZCTR number, ACTRN12614000110684; ClinicalTrials.gov number, NCT02446405; and EU Clinical Trials Register number, 2014-003190-42.).
Sections du résumé
BACKGROUND
Enzalutamide, an androgen-receptor inhibitor, has been associated with improved overall survival in men with castration-resistant prostate cancer. It is not known whether adding enzalutamide to testosterone suppression, with or without early docetaxel, will improve survival in men with metastatic, hormone-sensitive prostate cancer.
METHODS
In this open-label, randomized, phase 3 trial, we assigned patients to receive testosterone suppression plus either open-label enzalutamide or a standard nonsteroidal antiandrogen therapy (standard-care group). The primary end point was overall survival. Secondary end points included progression-free survival as determined by the prostate-specific antigen (PSA) level, clinical progression-free survival, and adverse events.
RESULTS
A total of 1125 men underwent randomization; the median follow-up was 34 months. There were 102 deaths in the enzalutamide group and 143 deaths in the standard-care group (hazard ratio, 0.67; 95% confidence interval [CI], 0.52 to 0.86; P = 0.002). Kaplan-Meier estimates of overall survival at 3 years were 80% (based on 94 events) in the enzalutamide group and 72% (based on 130 events) in the standard-care group. Better results with enzalutamide were also seen in PSA progression-free survival (174 and 333 events, respectively; hazard ratio, 0.39; P<0.001) and in clinical progression-free survival (167 and 320 events, respectively; hazard ratio, 0.40; P<0.001). Treatment discontinuation due to adverse events was more frequent in the enzalutamide group than in the standard-care group (33 events and 14 events, respectively). Fatigue was more common in the enzalutamide group; seizures occurred in 7 patients in the enzalutamide group (1%) and in no patients in the standard-care group.
CONCLUSIONS
Enzalutamide was associated with significantly longer progression-free and overall survival than standard care in men with metastatic, hormone-sensitive prostate cancer receiving testosterone suppression. The enzalutamide group had a higher incidence of seizures and other toxic effects, especially among those treated with early docetaxel. (Funded by Astellas Scientific and Medical Affairs and others; ENZAMET (ANZUP 1304) ANZCTR number, ACTRN12614000110684; ClinicalTrials.gov number, NCT02446405; and EU Clinical Trials Register number, 2014-003190-42.).
Identifiants
pubmed: 31157964
doi: 10.1056/NEJMoa1903835
doi:
Substances chimiques
Androgen Receptor Antagonists
0
Benzamides
0
Nitriles
0
Phenylthiohydantoin
2010-15-3
enzalutamide
93T0T9GKNU
Banques de données
ANZCTR
['ACTRN12614000110684']
ClinicalTrials.gov
['NCT02446405']
EudraCT
['2014-003190-42']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
121-131Subventions
Organisme : Canadian Cancer Society
ID : 704970
Pays : International
Organisme : Cancer Australia
ID : Support for Cancer Clinical Trials Program
Pays : International
Organisme : National Health and Medical Research Council
ID : Practitioner Fellowship APP1102604
Pays : International
Organisme : National Health and Medical Research Council
ID : Program Grants 1037786 and 1150467
Pays : International
Investigateurs
Ehtesham Abdi
(E)
Suzanne Allan
(S)
Patricia Bastick
(P)
Stephen Begbie
(S)
Robert Blum
(R)
Karen Briscoe
(K)
Daniel Brungs
(D)
Sean Bydder
(S)
Bala Renuka Chittajallu
(BR)
Michelle Cronk
(M)
Katharine Cuff
(K)
Ian Davis
(I)
Anthony Dowling
(A)
Mark Frydenberg
(M)
Matthew George
(M)
Lisa Horvath
(L)
Elizabeth Hovey
(E)
Anthony Joshua
(A)
Narayan Karanth
(N)
Ganessan Kichenadasse
(G)
Laurence Krieger
(L)
Gavin Marx
(G)
Maitham Mathlum
(M)
Louise Nott
(L)
Zulfiquer Otty
(Z)
Francis Parnis
(F)
David Pook
(D)
Shahneen Sandhu
(S)
Sanjeev Sewak
(S)
Amanda Stevanovic
(A)
Martin Stockler
(M)
Aneta Suder
(A)
Hsiang Tan
(H)
Javier Torres
(J)
Simon Troon
(S)
Craig Underhill
(C)
Andrew Weickhardt
(A)
Robert Zielinski
(R)
Tahir Abbas
(T)
Ghadeer Anan
(G)
Chris Booth
(C)
Holly Campbell
(H)
Kim Chi
(K)
Joseph Chin
(J)
Edmond Chouinard
(E)
Bryan Donnelly
(B)
Darrel Drachenberg
(D)
Amir Faghih
(A)
Antonio Finelli
(A)
Sebastien Hotte
(S)
Krista Noonan
(K)
Scott North
(S)
Mohammad Rassouli
(M)
Neil Reaume
(N)
Ricardo Rendon
(R)
Fred Saad
(F)
Evgeny Sadikov
(E)
Eric Vigneault
(E)
Pawel Zalewski
(P)
John McCaffrey
(J)
Ray McDermott
(R)
Patrick Morris
(P)
Miriam O'Connor
(M)
Paul Donnellan
(P)
Dearbhaile O'Donnell
(D)
Jim Edwards
(J)
Peter Fong
(P)
Alvin Tan
(A)
Simon Chowdhury
(S)
Simon Crabb
(S)
Omar Khan
(O)
Vincent Khoo
(V)
Graham Macdonald
(G)
Heather Payne
(H)
Angus Robinson
(A)
Jonathon Shamash
(J)
John Staffurth
(J)
Carys Thomas
(C)
Alastair Thomson
(A)
Christopher Sweeney
(C)
Guy Toner
(G)
Glenn Ferguson
(G)
Giuseppe Esposito
(G)
Martin Dowling
(M)
Lucy Byers
(L)
Christine Garforth
(C)
Nicole Tankard
(N)
Vera Terry
(V)
Burcu Vachan
(B)
Diana Winter
(D)
Sarah Finlayson
(S)
Salma Fahridin
(S)
Georgina Dukoska
(G)
Leanna Cheung
(L)
Ashneeta Kumar
(A)
David Espinoza
(D)
Liz Barnes
(L)
Vanessa Cochrane
(V)
Alexander Montenegro
(A)
Maxwell Sherry
(M)
Paul Stos
(P)
Olwyn Deignan
(O)
Eibhlín Mulroe
(E)
Kathleen Scott
(K)
Paul Nguyen
(P)
Ian Olver
(I)
Richard Bell
(R)
Peta Forder
(P)
Commentaires et corrections
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Informations de copyright
Copyright © 2019 Massachusetts Medical Society.