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dc.contributor.authorArmstrong, AJ
dc.contributor.authorSaad, F
dc.contributor.authorPhung, D
dc.contributor.authorDmuchowski, C
dc.contributor.authorShore, ND
dc.contributor.authorFizazi, K
dc.contributor.authorHirmand, M
dc.contributor.authorForer, D
dc.contributor.authorScher, HI
dc.contributor.authorBono, JD
dc.date.accessioned2017-08-14T14:15:05Z
dc.date.issued2017-06
dc.identifier.citationCancer, 2017, 123 (12), pp. 2303 - 2311
dc.identifier.issn0008-543X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/775
dc.identifier.eissn1097-0142
dc.identifier.doi10.1002/cncr.30587
dc.description.abstractBackground In the AFFIRM trial, enzalutamide significantly increased overall survival (OS) for men with metastatic castration-resistant prostate cancer (mCRPC) after chemotherapy versus placebo and significantly decreased prostate-specific antigen (PSA) levels. The goal of this post hoc analysis was to associate levels of PSA decline from baseline after enzalutamide with clinical outcomes in the postchemotherapy mCRPC setting.Methods Men in the AFFIRM trial (n = 1199) were grouped by maximal PSA decline in the first 90 days of treatment. Kaplan-Meier estimates evaluated the association of defined PSA changes from baseline with OS, progression-free survival (PFS), radiographic PFS (rPFS), and pain response. Each PSA decline category was assessed for OS surrogacy using Prentice criteria, proportion of treatment effect explained (PTE), and proportion of variation explained.Results Men treated with enzalutamide had improved OS (hazard ratio, 0.63; P < .001) and higher rates of PSA decline (odds ratio, >19.0; P < .001) versus placebo. PSA declines of any, ≥30%, ≥50%, and ≥90% with enzalutamide were strongly associated with greater OS, PSA PFS, rPFS (P < .001), and pain response (P < .026) versus PSA increase/no decline. Any, ≥30%, and ≥50% declines in PSA resulted in the PTE range of 1.07-1.29, where treatment was no longer significant after adjustment for decline measures (P > .20).Conclusions PSA declines of any, ≥30%, and ≥50% following enzalutamide were associated with greater clinical and pain response and improvements in PFS and OS. Surrogacy of PSA decline for OS was not fully established, possibly due to lack of PSA declines with placebo, and discordant results between PSA and imaging responses over time, and because some declines were not durable due to rapid resistance development. However, a lack of PSA decline by 90 days following enzalutamide treatment was a poor prognosis indicator in this setting. Conclusions from sensitivity analyses of maximal PSA decline from baseline over the entire treatment period are consistent with PSA declines restricted to the first 90 days. Cancer 2017;123:2303-2311. © 2017 American Cancer Society.
dc.formatPrint-Electronic
dc.format.extent2303 - 2311
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectCarcinoma
dc.subjectTaxoids
dc.subjectPhenylthiohydantoin
dc.subjectKallikreins
dc.subjectProstate-Specific Antigen
dc.subjectAntineoplastic Agents
dc.subjectDisease-Free Survival
dc.subjectTreatment Outcome
dc.subjectSurvival Rate
dc.subjectProportional Hazards Models
dc.subjectDouble-Blind Method
dc.subjectMale
dc.subjectKaplan-Meier Estimate
dc.subjectProstatic Neoplasms, Castration-Resistant
dc.subjectDocetaxel
dc.titleClinical outcomes and survival surrogacy studies of prostate-specific antigen declines following enzalutamide in men with metastatic castration-resistant prostate cancer previously treated with docetaxel.
dc.typeJournal Article
dcterms.dateAccepted2016-12-23
rioxxterms.versionofrecord10.1002/cncr.30587
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
rioxxterms.licenseref.startdate2017-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer
pubs.issue12
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.publication-statusPublished
pubs.volume123en_US
pubs.embargo.termsNo embargo
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
dc.contributor.icrauthorDe Bono, Johannen


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