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dc.contributor.authorSmith, Men_US
dc.contributor.authorDe Bono, Jen_US
dc.contributor.authorSternberg, Cen_US
dc.contributor.authorLe Moulec, Sen_US
dc.contributor.authorOudard, Sen_US
dc.contributor.authorDe Giorgi, Uen_US
dc.contributor.authorKrainer, Men_US
dc.contributor.authorBergman, Aen_US
dc.contributor.authorHoelzer, Wen_US
dc.contributor.authorDe Wit, Ren_US
dc.contributor.authorBögemann, Men_US
dc.contributor.authorSaad, Fen_US
dc.contributor.authorCruciani, Gen_US
dc.contributor.authorThiery-Vuillemin, Aen_US
dc.contributor.authorFeyerabend, Sen_US
dc.contributor.authorMiller, Ken_US
dc.contributor.authorHouédé, Nen_US
dc.contributor.authorHussain, Sen_US
dc.contributor.authorLam, Een_US
dc.contributor.authorPolikoff, Jen_US
dc.contributor.authorStenzl, Aen_US
dc.contributor.authorMainwaring, Pen_US
dc.contributor.authorRamies, Den_US
dc.contributor.authorHessel, Cen_US
dc.contributor.authorWeitzman, Aen_US
dc.contributor.authorFizazi, Ken_US
dc.date.accessioned2017-03-01T13:53:33Z
dc.date.issued2016-09en_US
dc.identifier.citationJournal of clinical oncology : official journal of the American Society of Clinical Oncology, 2016, 34 (25), pp. 3005 - 3013en_US
dc.identifier.issn0732-183Xen_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/457
dc.identifier.eissn1527-7755en_US
dc.identifier.doi10.1200/jco.2015.65.5597en_US
dc.description.abstract<h4>Purpose</h4>Cabozantinib is an inhibitor of kinases, including MET and vascular endothelial growth factor receptors, and has shown activity in men with previously treated metastatic castration-resistant prostate cancer (mCRPC). This blinded phase III trial compared cabozantinib with prednisone in patients with mCRPC.<h4>Patients and methods</h4>Men with progressive mCRPC after docetaxel and abiraterone and/or enzalutamide were randomly assigned at a two-to-one ratio to cabozantinib 60 mg once per day or prednisone 5 mg twice per day. The primary end point was overall survival (OS). Bone scan response (BSR) at week 12 as assessed by independent review committee was the secondary end point; radiographic progression-free survival (rPFS) and effects on circulating tumor cells (CTCs), bone biomarkers, serum prostate-specific antigen (PSA), and symptomatic skeletal events (SSEs) were exploratory assessments.<h4>Results</h4>A total of 1,028 patients were randomly assigned to cabozantinib (n = 682) or prednisone (n = 346). Median OS was 11.0 months with cabozantinib and 9.8 months with prednisone (hazard ratio, 0.90; 95% CI, 0.76 to 1.06; stratified log-rank P = .213). BSR at week 12 favored cabozantinib (42% v 3%; stratified Cochran-Mantel-Haenszel P < .001). rPFS was improved in the cabozantinib group (median, 5.6 v 2.8 months; hazard ratio, 0.48; 95% CI, 0.40 to 0.57; stratified log-rank P < .001). Cabozantinib was associated with improvements in CTC conversion, bone biomarkers, and post-random assignment incidence of SSEs but not PSA outcomes. Grade 3 to 4 adverse events and discontinuations because of adverse events were higher with cabozantinib than with prednisone (71% v 56% and 33% v 12%, respectively).<h4>Conclusion</h4>Cabozantinib did not significantly improve OS compared with prednisone in heavily treated patients with mCRPC and progressive disease after docetaxel and abiraterone and/or enzalutamide. Cabozantinib had some activity in improving BSR, rPFS, SSEs, CTC conversions, and bone biomarkers but not PSA outcomes.en_US
dc.formatPrint-Electronicen_US
dc.format.extent3005 - 3013en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.subjectHumansen_US
dc.subjectNeoplasm Metastasisen_US
dc.subjectAnilidesen_US
dc.subjectPyridinesen_US
dc.subjectPrednisoneen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectProtein Kinase Inhibitorsen_US
dc.subjectDisease-Free Survivalen_US
dc.subjectSurvival Rateen_US
dc.subjectDouble-Blind Methoden_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectAged, 80 and overen_US
dc.subjectMiddle Ageden_US
dc.subjectMaleen_US
dc.subjectNeoplastic Cells, Circulatingen_US
dc.subjectProstatic Neoplasms, Castration-Resistanten_US
dc.subjectBiomarkers, Tumoren_US
dc.titlePhase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1200/jco.2015.65.5597en_US
rioxxterms.licenseref.startdate2016-09en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfJournal of clinical oncology : official journal of the American Society of Clinical Oncologyen_US
pubs.issue25en_US
pubs.notesNo embargoen_US
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-statusPublisheden_US
pubs.volume34en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
dc.contributor.icrauthorDe Bono, Johannen_US


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