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dc.contributor.authorJoshua, AM
dc.contributor.authorArmstrong, A
dc.contributor.authorCrumbaker, M
dc.contributor.authorScher, HI
dc.contributor.authorde Bono, J
dc.contributor.authorTombal, B
dc.contributor.authorHussain, M
dc.contributor.authorSternberg, CN
dc.contributor.authorGillessen, S
dc.contributor.authorCarles, J
dc.contributor.authorFizazi, K
dc.contributor.authorLin, P
dc.contributor.authorDuggan, W
dc.contributor.authorSugg, J
dc.contributor.authorRussell, D
dc.contributor.authorBeer, TM
dc.coverage.spatialEngland
dc.date.accessioned2022-08-23T10:11:21Z
dc.date.available2022-08-23T10:11:21Z
dc.date.issued2022-07-01
dc.identifierS0959-8049(22)00206-4
dc.identifier.citationEuropean Journal of Cancer, 2022, 170 pp. 285 - 295en_US
dc.identifier.issn0959-8049
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5308
dc.identifier.eissn1879-0852
dc.identifier.eissn1879-0852
dc.identifier.doi10.1016/j.ejca.2022.04.005
dc.description.abstractBACKGROUND: Statins and metformin are commonly prescribed for patients, including those with prostate cancer. Preclinical and epidemiologic studies of each agent have suggested anti-cancer properties. METHODS: Patient data from three randomised, double-blind, placebo-controlled, phase III studies evaluating enzalutamide (AFFIRM, PREVAIL and PROSPER) in patients with castration-resistant prostate cancer were included in this analysis. This post hoc, retrospective study examined the association of statin and metformin on radiographic progression-free survival (rPFS), metastasis-free survival (MFS), toxicity and overall survival (OS). After adjusting for available clinical prognostic variables, multivariate analyses were performed on pooled data from AFFIRM and PREVAIL, all three trials pooled, and each trial individually, to assess differential efficacy in these end-points associated with the baseline use of these medications. RESULTS: In the multivariate analysis of the individual trials, OS and rPFS/MFS were not significantly influenced by statin or metformin use in AFFIRM or PROSPER. However, in PREVAIL, OS was significantly influenced by statin (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.59-0.89) and rPFS was significantly influenced by metformin (HR, 0.48; 95% CI 0.34-0.70). In pooled analyses, improved OS was significantly associated with statin use but not metformin use for AFFIRM+PREVAIL trials (HR 0.83; 95% CI 0.72-0.96) and AFFIRM+PREVAIL+PROSPER (HR 0.75; 95% CI 0.66-0.85). CONCLUSIONS: The association between statin or metformin use and rPFS, MFS and OS was inconsistent across three trials. Analyses of all three trials pooled and AFFIRM+PREVAIL pooled revealed that statin but not metformin use was significantly associated with a reduced risk of death in enzalutamide-treated patients. Additional prospective, controlled studies are warranted. CLINICAL TRIAL REGISTRATION: AFFIRM (NCT00974311), PREVAIL (NCT01212991) and PROSPER (NCT02003924).
dc.formatPrint-Electronic
dc.format.extent285 - 295
dc.languageeng
dc.language.isoengen_US
dc.publisherELSEVIER SCI LTDen_US
dc.relation.ispartofEuropean Journal of Cancer
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0en_US
dc.subjectCastration-resistant prostate cancer
dc.subjectEnzalutamide
dc.subjectMetformin
dc.subjectOverall survival
dc.subjectRadiographic progression-free survival
dc.subjectStatin
dc.subjectAntineoplastic Agents
dc.subjectBenzamides
dc.subjectDisease-Free Survival
dc.subjectHumans
dc.subjectHydroxymethylglutaryl-CoA Reductase Inhibitors
dc.subjectMale
dc.subjectMetformin
dc.subjectNitriles
dc.subjectPhenylthiohydantoin
dc.subjectProspective Studies
dc.subjectProstatic Neoplasms, Castration-Resistant
dc.subjectRandomized Controlled Trials as Topic
dc.subjectRetrospective Studies
dc.subjectTreatment Outcome
dc.titleStatin and metformin use and outcomes in patients with castration-resistant prostate cancer treated with enzalutamide: A meta-analysis of AFFIRM, PREVAIL and PROSPER.en_US
dc.typeJournal Article
dcterms.dateAccepted2022-04-01
dc.date.updated2022-08-23T10:10:37Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1016/j.ejca.2022.04.005en_US
rioxxterms.licenseref.startdate2022-07-01
rioxxterms.typeJournal Article/Reviewen_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/35643841
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.volume170
icr.researchteamPrCa Targeted Therapyen_US
dc.contributor.icrauthorDe Bono, Johann
icr.provenanceDeposited by Mr Arek Surman on 2022-08-23. Deposit type is initial. No. of files: 1. Files: 1-s2.0-S0959804922002064-main.pdf


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