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dc.contributor.authorLong, GVen_US
dc.contributor.authorHauschild, Aen_US
dc.contributor.authorSantinami, Men_US
dc.contributor.authorAtkinson, Ven_US
dc.contributor.authorMandalà, Men_US
dc.contributor.authorChiarion-Sileni, Ven_US
dc.contributor.authorLarkin, Jen_US
dc.contributor.authorNyakas, Men_US
dc.contributor.authorDutriaux, Cen_US
dc.contributor.authorHaydon, Aen_US
dc.contributor.authorRobert, Cen_US
dc.contributor.authorMortier, Len_US
dc.contributor.authorSchachter, Jen_US
dc.contributor.authorSchadendorf, Den_US
dc.contributor.authorLesimple, Ten_US
dc.contributor.authorPlummer, Ren_US
dc.contributor.authorJi, Ren_US
dc.contributor.authorZhang, Pen_US
dc.contributor.authorMookerjee, Ben_US
dc.contributor.authorLegos, Jen_US
dc.contributor.authorKefford, Ren_US
dc.contributor.authorDummer, Ren_US
dc.contributor.authorKirkwood, JMen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2018-03-02T12:58:02Z
dc.date.issued2017-11-09en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28891408en_US
dc.identifier.citationN Engl J Med, 2017, 377 (19), pp. 1813 - 1823en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1493
dc.identifier.eissn1533-4406en_US
dc.identifier.doi10.1056/NEJMoa1708539en_US
dc.description.abstractBACKGROUND: Combination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We sought to determine whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations. METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 870 patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to receive oral dabrafenib at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy, 438 patients) or two matched placebo tablets (432 patients) for 12 months. The primary end point was relapse-free survival. Secondary end points included overall survival, distant metastasis-free survival, freedom from relapse, and safety. RESULTS: At a median follow-up of 2.8 years, the estimated 3-year rate of relapse-free survival was 58% in the combination-therapy group and 39% in the placebo group (hazard ratio for relapse or death, 0.47; 95% confidence interval [CI], 0.39 to 0.58; P<0.001). The 3-year overall survival rate was 86% in the combination-therapy group and 77% in the placebo group (hazard ratio for death, 0.57; 95% CI, 0.42 to 0.79; P=0.0006), but this level of improvement did not cross the prespecified interim analysis boundary of P=0.000019. Rates of distant metastasis-free survival and freedom from relapse were also higher in the combination-therapy group than in the placebo group. The safety profile of dabrafenib plus trametinib was consistent with that observed with the combination in patients with metastatic melanoma. CONCLUSIONS: Adjuvant use of combination therapy with dabrafenib plus trametinib resulted in a significantly lower risk of recurrence in patients with stage III melanoma with BRAF V600E or V600K mutations than the adjuvant use of placebo and was not associated with new toxic effects. (Funded by GlaxoSmithKline and Novartis; COMBI-AD ClinicalTrials.gov, NCT01682083 ; EudraCT number, 2012-001266-15 .).en_US
dc.format.extent1813 - 1823en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectAdjuvants, Immunologicen_US
dc.subjectAdolescenten_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectAged, 80 and overen_US
dc.subjectAntineoplastic Combined Chemotherapy Protocolsen_US
dc.subjectDouble-Blind Methoden_US
dc.subjectFemaleen_US
dc.subjectHumansen_US
dc.subjectImidazolesen_US
dc.subjectMaleen_US
dc.subjectMelanomaen_US
dc.subjectMiddle Ageden_US
dc.subjectMutationen_US
dc.subjectNeoplasm Recurrence, Localen_US
dc.subjectNeoplasm Stagingen_US
dc.subjectOximesen_US
dc.subjectProto-Oncogene Proteins B-rafen_US
dc.subjectPyridonesen_US
dc.subjectPyrimidinonesen_US
dc.subjectSkin Neoplasmsen_US
dc.subjectSurvival Analysisen_US
dc.subjectYoung Adulten_US
dc.titleAdjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1056/NEJMoa1708539en_US
rioxxterms.licenseref.startdate2017-11-09en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfN Engl J Meden_US
pubs.issue19en_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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume377en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMelanoma and Kidney Canceren_US
dc.contributor.icrauthorLarkin, Jamesen_US
dc.contributor.icrauthorMarsden,en_US


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