Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer

Background: Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis. Metho...

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Autores: Smith, Matthew R., Saad, Fred, Chowdhury, Simon, Oudard, Stephane, Hadaschik, Boris A., Graff, Julie N., Olmos, David, SPARTAN Investigators, Sánchez Sánchez, Ernesto, Small, Eric J.
Tipo de documento: artigo
Estado:Versión aceptada para publicación
Data de publicação:2018
País:España
Recursos:Universidad de Sevilla (US)
Repositório:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/181489
Acesso em linha:https://hdl.handle.net/11441/181489
https://doi.org/10.1056/NEJMoa1715546
Access Level:Acceso aberto
Palavra-chave:Apalutamide
Prostate cancer
Castration resistance
Metastasis
Metastasis-free survival
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spelling Apalutamide Treatment and Metastasis-free Survival in Prostate CancerSmith, Matthew R.Saad, FredChowdhury, SimonOudard, StephaneHadaschik, Boris A.Graff, Julie N.Olmos, DavidSPARTAN InvestigatorsSánchez Sánchez, ErnestoSmall, Eric J.ApalutamideProstate cancerCastration resistanceMetastasisMetastasis-free survivalBackground: Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis. Methods: We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death. Results: A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%). Conclusions: Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo. (Funded by Janssen Research and Development; SPARTAN ClinicalTrials.gov number, NCT01946204.)Massachusetts Medical SocietyCirugíaAstellasAstraZenecaBayerBristol-Myers SquibbClovis OncologyDendreonGenentechIpsenJohnson JohnsonJohnson JohnsonMerckNovartis2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/181489https://doi.org/10.1056/NEJMoa1715546reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésThe New England Journal of Medicine, 378 (15), 1408-1418.https://www.nejm.org/doi/10.1056/NEJMoa1715546info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1814892026-06-17T12:51:07Z
dc.title.none.fl_str_mv Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer
title Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer
spellingShingle Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer
Smith, Matthew R.
Apalutamide
Prostate cancer
Castration resistance
Metastasis
Metastasis-free survival
title_short Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer
title_full Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer
title_fullStr Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer
title_full_unstemmed Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer
title_sort Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer
dc.creator.none.fl_str_mv Smith, Matthew R.
Saad, Fred
Chowdhury, Simon
Oudard, Stephane
Hadaschik, Boris A.
Graff, Julie N.
Olmos, David
SPARTAN Investigators
Sánchez Sánchez, Ernesto
Small, Eric J.
author Smith, Matthew R.
author_facet Smith, Matthew R.
Saad, Fred
Chowdhury, Simon
Oudard, Stephane
Hadaschik, Boris A.
Graff, Julie N.
Olmos, David
SPARTAN Investigators
Sánchez Sánchez, Ernesto
Small, Eric J.
author_role author
author2 Saad, Fred
Chowdhury, Simon
Oudard, Stephane
Hadaschik, Boris A.
Graff, Julie N.
Olmos, David
SPARTAN Investigators
Sánchez Sánchez, Ernesto
Small, Eric J.
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Cirugía
Astellas
AstraZeneca
Bayer
Bristol-Myers Squibb
Clovis Oncology
Dendreon
Genentech
Ipsen
Johnson Johnson
Johnson Johnson
Merck
Novartis
dc.subject.none.fl_str_mv Apalutamide
Prostate cancer
Castration resistance
Metastasis
Metastasis-free survival
topic Apalutamide
Prostate cancer
Castration resistance
Metastasis
Metastasis-free survival
description Background: Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis. Methods: We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death. Results: A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%). Conclusions: Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo. (Funded by Janssen Research and Development; SPARTAN ClinicalTrials.gov number, NCT01946204.)
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/181489
https://doi.org/10.1056/NEJMoa1715546
url https://hdl.handle.net/11441/181489
https://doi.org/10.1056/NEJMoa1715546
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv The New England Journal of Medicine, 378 (15), 1408-1418.
https://www.nejm.org/doi/10.1056/NEJMoa1715546
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Massachusetts Medical Society
publisher.none.fl_str_mv Massachusetts Medical Society
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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