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dc.contributor.authorCameron, Den_US
dc.contributor.authorPiccart-Gebhart, MJen_US
dc.contributor.authorGelber, RDen_US
dc.contributor.authorProcter, Men_US
dc.contributor.authorGoldhirsch, Aen_US
dc.contributor.authorde Azambuja, Een_US
dc.contributor.authorCastro, Gen_US
dc.contributor.authorUntch, Men_US
dc.contributor.authorSmith, Ien_US
dc.contributor.authorGianni, Len_US
dc.contributor.authorBaselga, Jen_US
dc.contributor.authorAl-Sakaff, Nen_US
dc.contributor.authorLauer, Sen_US
dc.contributor.authorMcFadden, Een_US
dc.contributor.authorLeyland-Jones, Ben_US
dc.contributor.authorBell, Ren_US
dc.contributor.authorDowsett, Men_US
dc.contributor.authorJackisch, Cen_US
dc.contributor.authorHerceptin Adjuvant (HERA) Trial Study Teamen_US
dc.date.accessioned2017-07-19T17:16:46Z
dc.date.issued2017-03en_US
dc.identifier.citationLancet (London, England), 2017, 389 (10075), pp. 1195 - 1205en_US
dc.identifier.issn0140-6736en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/731
dc.identifier.eissn1474-547Xen_US
dc.identifier.doi10.1016/s0140-6736(16)32616-2en_US
dc.description.abstractBACKGROUND:Clinical trials have shown that trastuzumab, a recombinant monoclonal antibody against HER2 receptor, significantly improves overall survival and disease-free survival in women with HER2-positive early breast cancer, but long-term follow-up data are needed. We report the results of comparing observation with two durations of trastuzumab treatment at a median follow-up of 11 years, for patients enrolled in the HERA (HERceptin Adjuvant) trial. METHODS:HERA (BIG 1-01) is an international, multicentre, open-label, phase 3 randomised trial of 5102 women with HER2-positive early breast cancer, who were enrolled from hospitals in 39 countries between Dec 7, 2001, and June 20, 2005. After completion of all primary therapy (including, surgery, chemotherapy, and radiotherapy as indicated), patients were randomly assigned (1:1:1) to receive trastuzumab for 1 year (once at 8 mg/kg of bodyweight intravenously, then 6 mg/kg once every 3 weeks) or for 2 years (with the same dose schedule), or to the observation group. Primary endpoint is disease-free survival, and analyses are in the intention-to-treat population. Hazard ratios (HRs) were estimated from Cox models, and survival curves were estimated by the Kaplan-Meier method. Comparison of 2 years versus 1 year of trastuzumab is based on 366-day landmark analyses. This study is registered with ClinicalTrials.gov (NCT00045032). FINDINGS:Of the 5102 women randomly assigned in the HERA trial, three patients had no evidence of having provided written informed consent to participate. We followed up the intention-to-treat population of 5099 patients (1697 in observation, 1702 in 1-year trastuzumab, and 1700 in 2-years trastuzumab groups). After a median follow-up of 11 years (IQR 10·09-11·53), random assignment to 1 year of trastuzumab significantly reduced the risk of a disease-free survival event (HR 0·76, 95% CI 0·68-0·86) and death (0·74, 0·64-0·86) compared with observation. 2 years of adjuvant trastuzumab did not improve disease free-survival outcomes compared with 1 year of this drug (HR 1·02, 95% CI 0·89-1·17). Estimates of 10-year disease-free survival were 63% for observation, 69% for 1 year of trastuzumab, and 69% for 2 years of trastuzumab. 884 (52%) patients assigned to the observation group selectively crossed over to receive trastuzumab. Cardiac toxicity remained low in all groups and occurred mostly during the treatment phase. The incidence of secondary cardiac endpoints was 122 (7·3%) in the 2-years trastuzumab group, 74 (4·4%) in the 1-year trastuzumab group, and 15 (0·9%) in the observation group. INTERPRETATION:1 year of adjuvant trastuzumab after chemotherapy for patients with HER2-positive early breast cancer significantly improves long-term disease-free survival, compared with observation. 2 years of trastuzumab had no additional benefit. FUNDING:F Hoffmann-La Roche (Roche).en_US
dc.formatPrint-Electronicen_US
dc.format.extent1195 - 1205en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.subjectHerceptin Adjuvant (HERA) Trial Study Teamen_US
dc.subjectHumansen_US
dc.subjectBreast Neoplasmsen_US
dc.subjectHeart Diseasesen_US
dc.subjectReceptor, erbB-2en_US
dc.subjectTreatment Outcomeen_US
dc.subjectChemotherapy, Adjuvanten_US
dc.subjectDrug Administration Scheduleen_US
dc.subjectFollow-Up Studiesen_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectMiddle Ageden_US
dc.subjectFemaleen_US
dc.subjectKaplan-Meier Estimateen_US
dc.subjectBiomarkers, Tumoren_US
dc.subjectTrastuzumaben_US
dc.subjectAntineoplastic Agents, Immunologicalen_US
dc.title11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-10-04en_US
rioxxterms.versionofrecord10.1016/s0140-6736(16)32616-2en_US
rioxxterms.licenseref.startdate2017-03en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfLancet (London, England)en_US
pubs.issue10075en_US
pubs.notesNot knownen_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/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume389en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorDowsett, Mitchen_US
dc.contributor.icrauthorSmith, Ianen_US
dc.contributor.icrauthorMarsden,en_US


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