Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer.
Aged
Aged, 80 and over
Antineoplastic Agents
/ adverse effects
Ataxia Telangiectasia Mutated Proteins
/ genetics
Bridged-Ring Compounds
/ therapeutic use
Cyclin-Dependent Kinases
/ genetics
Genes, BRCA1
Humans
Male
Middle Aged
Mutation
Neoplasm Metastasis
/ drug therapy
Phthalazines
/ adverse effects
Piperazines
/ adverse effects
Prostatic Neoplasms, Castration-Resistant
/ drug therapy
Survival Analysis
Taxoids
/ therapeutic use
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:
10 12 2020
10 12 2020
Historique:
pubmed:
22
9
2020
medline:
29
12
2020
entrez:
21
9
2020
Statut:
ppublish
Résumé
We previously reported that olaparib led to significantly longer imaging-based progression-free survival than the physician's choice of enzalutamide or abiraterone among men with metastatic castration-resistant prostate cancer who had qualifying alterations in homologous recombination repair genes and whose disease had progressed during previous treatment with a next-generation hormonal agent. The results of the final analysis of overall survival have not yet been reported. In an open-label, phase 3 trial, we randomly assigned patients in a 2:1 ratio to receive olaparib (256 patients) or the physician's choice of enzalutamide or abiraterone plus prednisone as the control therapy (131 patients). Cohort A included 245 patients with at least one alteration in The median duration of overall survival in cohort A was 19.1 months with olaparib and 14.7 months with control therapy (hazard ratio for death, 0.69; 95% confidence interval [CI], 0.50 to 0.97; P = 0.02). In cohort B, the median duration of overall survival was 14.1 months with olaparib and 11.5 months with control therapy. In the overall population (cohorts A and B), the corresponding durations were 17.3 months and 14.0 months. Overall, 86 of 131 patients (66%) in the control group crossed over to receive olaparib (56 of 83 patients [67%] in cohort A). A sensitivity analysis that adjusted for crossover to olaparib showed hazard ratios for death of 0.42 (95% CI, 0.19 to 0.91) in cohort A, 0.83 (95% CI, 0.11 to 5.98) in cohort B, and 0.55 (95% CI, 0.29 to 1.06) in the overall population. Among men with metastatic castration-resistant prostate cancer who had tumors with at least one alteration in
Sections du résumé
BACKGROUND
We previously reported that olaparib led to significantly longer imaging-based progression-free survival than the physician's choice of enzalutamide or abiraterone among men with metastatic castration-resistant prostate cancer who had qualifying alterations in homologous recombination repair genes and whose disease had progressed during previous treatment with a next-generation hormonal agent. The results of the final analysis of overall survival have not yet been reported.
METHODS
In an open-label, phase 3 trial, we randomly assigned patients in a 2:1 ratio to receive olaparib (256 patients) or the physician's choice of enzalutamide or abiraterone plus prednisone as the control therapy (131 patients). Cohort A included 245 patients with at least one alteration in
RESULTS
The median duration of overall survival in cohort A was 19.1 months with olaparib and 14.7 months with control therapy (hazard ratio for death, 0.69; 95% confidence interval [CI], 0.50 to 0.97; P = 0.02). In cohort B, the median duration of overall survival was 14.1 months with olaparib and 11.5 months with control therapy. In the overall population (cohorts A and B), the corresponding durations were 17.3 months and 14.0 months. Overall, 86 of 131 patients (66%) in the control group crossed over to receive olaparib (56 of 83 patients [67%] in cohort A). A sensitivity analysis that adjusted for crossover to olaparib showed hazard ratios for death of 0.42 (95% CI, 0.19 to 0.91) in cohort A, 0.83 (95% CI, 0.11 to 5.98) in cohort B, and 0.55 (95% CI, 0.29 to 1.06) in the overall population.
CONCLUSIONS
Among men with metastatic castration-resistant prostate cancer who had tumors with at least one alteration in
Identifiants
pubmed: 32955174
doi: 10.1056/NEJMoa2022485
doi:
Substances chimiques
Antineoplastic Agents
0
Bridged-Ring Compounds
0
Phthalazines
0
Piperazines
0
Taxoids
0
taxane
1605-68-1
ATM protein, human
EC 2.7.11.1
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
CDK12 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinases
EC 2.7.11.22
olaparib
WOH1JD9AR8
Banques de données
ClinicalTrials.gov
['NCT02987543']
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
2345-2357Subventions
Organisme : AstraZeneca
ID : NA
Pays : International
Organisme : Merck Sharp and Dohme
ID : NA
Pays : International
Investigateurs
Gabriela Gatica
(G)
Diego Kaen
(D)
Ernesto Korbenfeld
(E)
Luis Montes de Oca
(L)
Sandra Anabel Ostoich
(SA)
Juan Sade
(J)
Pretoria Bilinski
(P)
Craig Gedye
(C)
Howard Gurney
(H)
Elizabeth Hovey
(E)
Edmond Kwan
(E)
Siobhan Ng
(S)
Shahneen Sandhu
(S)
Lavinia Spain
(L)
Aneta Suder
(A)
Thean Hsiang Tan
(TH)
Richard Greil
(R)
Gero Kramer
(G)
Wolfgang Loidl
(W)
Johannes Meran
(J)
Herbert Stöger
(H)
Felipe Cruz
(F)
Diogo da Rosa
(D)
Charles de Padua
(C)
Gabriel Dos Anjos
(G)
Adilson Faccio
(A)
Andre Fay
(A)
Marcelo Freitas
(M)
Gustavo Girotto
(G)
Fabrício Augusto Oliveira
(FA)
Suelen Martins
(S)
Marcelo Salgado
(M)
Fabio Schutz
(F)
Rodrigo Villarroel
(R)
Luis Zucca
(L)
Richard Casey
(R)
Kim Chi
(K)
Susan Ellard
(S)
Urban Emmenegger
(U)
Antonio Finelli
(A)
Sebastien Hotte
(S)
Nayyer Iqbal
(N)
Michael Kolinsky
(M)
Louis Lacombe
(L)
Jean-Benoit Paradis
(JB)
Fred Saad
(F)
Simon Tanguay
(S)
Steinbjørn Hansen
(S)
Jerome Alexandre
(J)
Emmanuelle Bompas
(E)
Karim Fizazi
(K)
Aude Flechon
(A)
Gwenaelle Gravis
(G)
Florence Joly
(F)
Vincent Massard
(V)
Loïc Mourey
(L)
Nicolas Penel
(N)
Guilhem Roubaud
(G)
Antoine Thiery-Vuillemin
(A)
Diego Tosi
(D)
Jean-Marc Tourani
(JM)
Manfred Binder
(M)
Thomas Ebert
(T)
Susan Feyerabend
(S)
Jochen Gleissner
(J)
Marc-Oliver Grimm
(MO)
Carsten Grüllich
(C)
Eva Hellmis
(E)
Wolfgang Hölzer
(W)
Jörg Klier
(J)
Stefan Machtens
(S)
Gerald Mickisch
(G)
Günter Niegisch
(G)
Martin Schostak
(M)
Arnulf Stenzl
(A)
Henrik Suttmann
(H)
Raanan Berger
(R)
Stephen Frank
(S)
Daniel Kejzman
(D)
Avivit Peer
(A)
Eli Rosenbaum
(E)
Avishay Sella
(A)
Rossana Berardi
(R)
Orazio Caffo
(O)
Ugo de Giorgi
(U)
Gaetano Facchini
(G)
Alketa Hamzaj
(A)
Emanuele Naglieri
(E)
Franco Nolè
(F)
Giuseppe Procopio
(G)
Roberto Sabbatini
(R)
Francesca Valcamonico
(F)
Shin Egawa
(S)
Masatoshi Eto
(M)
Yasuhisa Fujii
(Y)
Kiyohide Fujimoto
(K)
Takayuki Goto
(T)
Katsuyoshi Hashine
(K)
Masashi Kato
(M)
Satoru Kawakami
(S)
Yukihiro Kondo
(Y)
Nobuaki Matsubara
(N)
Ryuji Matsumoto
(R)
Masato Matsuzaki
(M)
Atsushi Mizokami
(A)
Masayoshi Nagata
(M)
Kazuo Nishimura
(K)
Chikara Ohyama
(C)
Takatsugu Okegawa
(T)
Mototsugu Oya
(M)
Hideki Sakai
(H)
Norihito Soga
(N)
Mikio Sugimoto
(M)
Hiroyoshi Suzuki
(H)
Kazuhiro Suzuki
(K)
Kenichi Tabata
(K)
Satoshi Tamada
(S)
Naoki Terada
(N)
Hiroji Uemura
(H)
Motohide Uemura
(M)
Junji Yonese
(J)
Kazuhiro Yoshimura
(K)
Daniel Heinrich
(D)
Young Deuk Choi
(YD)
Byung Ha Chung
(BH)
Hong Koo Ha
(HK)
Jun Hyuk Hong
(JH)
Seong Soo Jeon
(SS)
Jae Young Joung
(JY)
Taek Won Kang
(TW)
Tae Gyun Kwon
(TG)
Ji Youl Lee
(JY)
Juan Antonio Virizuela Echaburu
(JA)
Carlos Álvarez Fernández
(C)
Joan Carles Galcerán
(JC)
Daniel Castellano Gauna
(D)
Nuria Sala González
(N)
David Olmos Hidalgo
(D)
Javier Puente Vázquez
(J)
Enrique Castellanos
(E)
Ingela Lissbrant
(I)
Chung-Hsin Chen
(CH)
Po-Hui Chiang
(PH)
Hsiao-Jen Chung
(HJ)
See-Tong Pang
(ST)
Wen-Pin Su
(WP)
Pai-Fu Wang
(PF)
Shian-Shiang Wang
(SS)
Wen-Jeng Wu
(WJ)
Su- Peng Yeh
(SP)
Andries Bergman
(A)
Niven Mehra
(N)
Susanne Osanto
(S)
Metin Tascilar
(M)
Robbert van Alphen
(R)
Hendrik van den Berg
(H)
Cagatay Arslan
(C)
Irfan Cicin
(I)
Mustafa Erman
(M)
Fatih Kose
(F)
Nil Mandel
(N)
Mustafa Ozguroglu
(M)
Ali Sendur
(A)
Yuksel Urun
(Y)
Johann de Bono
(J)
Paul Elliott
(P)
Stephanie Gibbs
(S)
Mark Linch
(M)
Jonathan Shamash
(J)
Neeraj Agarwal
(N)
Andrew Armstrong
(A)
Vasileios Assikis
(V)
James Bailen
(J)
Michael Carducci
(M)
William Clark
(W)
Sarah Colonna
(S)
Gregory Daniels
(G)
Paromita Datta
(P)
Nancy Davis
(N)
Nancy Dawson
(N)
Tanya Dorff
(T)
Curtis Dunshee
(C)
Michael Goodman
(M)
Theodore Gourdin
(T)
Ivan Grunberger
(I)
Maha Hussain
(M)
Benjamin Martin
(B)
Bryan Mehlhaff
(B)
Gregory Merrick
(G)
Gregg Newman
(G)
Luke Nordquist
(L)
Yeun-Hee Park
(YH)
Kalpesh Patel
(K)
Christopher Pieczonka
(C)
Daniel Saltzstein
(D)
Oliver Sartor
(O)
Stephen Savage
(S)
Peter Schlegel
(P)
Ian Schnadig
(I)
David Shaffer
(D)
Neal Shore
(N)
Kelly Stratton
(K)
Ronald Tutrone
(R)
Daniel Vaena
(D)
Nicholas Vogelzang
(N)
Jingsong Zhang
(J)
Commentaires et corrections
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Informations de copyright
Copyright © 2020 Massachusetts Medical Society.