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dc.contributor.authorShah, MAen_US
dc.contributor.authorBang, Y-Jen_US
dc.contributor.authorLordick, Fen_US
dc.contributor.authorAlsina, Men_US
dc.contributor.authorChen, Men_US
dc.contributor.authorHack, SPen_US
dc.contributor.authorBruey, JMen_US
dc.contributor.authorSmith, Den_US
dc.contributor.authorMcCaffery, Ien_US
dc.contributor.authorShames, DSen_US
dc.contributor.authorPhan, Sen_US
dc.contributor.authorCunningham, Den_US
dc.date.accessioned2017-07-05T11:08:45Z
dc.date.issued2017-05en_US
dc.identifier.citationJAMA oncology, 2017, 3 (5), pp. 620 - 627en_US
dc.identifier.issn2374-2437en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/683
dc.identifier.eissn2374-2445en_US
dc.identifier.doi10.1001/jamaoncol.2016.5580en_US
dc.description.abstract<h4>Importance</h4>Dysregulation of the mesenchymal-epithelial transition (MET) signaling pathway is associated with poor prognosis in gastroesophageal adenocarcinoma (GEC). We report results of METGastric, a phase 3 trial of the MET inhibitor onartuzumab plus standard first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative, MET-positive, advanced GEC.<h4>Objective</h4>To determine whether the addition of onartuzumab to first-line fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) improves efficacy compared with mFOLFOX6 plus placebo in HER2-negative, MET-positive GEC.<h4>Design, setting, and participants</h4>Randomized, double-blind, multicenter trial conducted from November 2012 to March 2014. Patients were 18 years or older with an adenocarcinoma of the stomach or gastroesophageal junction with metastatic disease not amenable for curative therapy. Tumor samples were centrally tested for MET expression using Ventana anti-Total c-MET (SP44) rabbit monoclonal antibody, HER2 status, and Lauren histologic subtype. MET-positive tumors were defined as at least 50% of tumor cells showing weak, moderate, and/or strong staining intensity (MET 1+/2+/3+, respectively) by immunohistochemistry.<h4>Interventions</h4>Patients with HER2-negative, MET-positive GEC were enrolled and randomized 1:1 to receive mFOLFOX6 with or without onartuzumab (10 mg/kg).<h4>Main outcomes and measures</h4>Co-primary end points: overall survival in the intent-to-treat (ITT) population and in patients with MET 2+/3+ GEC. Secondary end points: progression-free survival (PFS), overall response rate (ORR), and safety.<h4>Results</h4>Enrollment was stopped early due to sponsor decision, which was agreed with an independent data monitoring committee. At the data cutoff (April 25, 2014) there were 562 patients in the ITT population (n = 283 placebo plus mFOLFOX6 [median age, 58 y; 65% male]; n = 279 onartuzumab plus mFOLFOX6 [median age, 60 y; 67% male]); 109 (38.5%) and 105 (37.6%) of the ITT population were MET 2+/3+, respectively. Addition of onartuzumab to mFOLFOX6 did not significantly improve OS, PFS, or ORR vs placebo plus mFOLFOX6 in the ITT (OS hazard ratio [HR], 0.82; 95% CI, 0.59-1.15; P = .24; PFS HR, 0.90; 95% CI, 0.71-1.16; P = .43; ORR, 46.1% vs 40.6%) or MET 2+/3+ populations (OS HR, 0.64; 95% CI, 0.40-1.03; P = .06; PFS HR, 0.79; 95% CI, 0.54-1.15; P = .22; ORR, 53.8% vs 44.6%). Safety was as expected for onartuzumab.<h4>Conclusions and relevance</h4>Addition of onartuzumab to first-line mFOLFOX6 did not significantly improve clinical benefits in the ITT or MET 2+/3+ populations.<h4>Trial registration</h4>clinicaltrials.gov Identifier: NCT01662869.en_US
dc.formatPrinten_US
dc.format.extent620 - 627en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.subjectEsophagogastric Junctionen_US
dc.subjectHumansen_US
dc.subjectAdenocarcinomaen_US
dc.subjectStomach Neoplasmsen_US
dc.subjectOrganoplatinum Compoundsen_US
dc.subjectFluorouracilen_US
dc.subjectLeucovorinen_US
dc.subjectReceptor, erbB-2en_US
dc.subjectAntineoplastic Combined Chemotherapy Protocolsen_US
dc.subjectAntibodies, Monoclonalen_US
dc.subjectDouble-Blind Methoden_US
dc.subjectAgeden_US
dc.subjectMiddle Ageden_US
dc.subjectFemaleen_US
dc.subjectMaleen_US
dc.subjectProto-Oncogene Proteins c-meten_US
dc.subjectIntention to Treat Analysisen_US
dc.subjectKaplan-Meier Estimateen_US
dc.subjectEpithelial-Mesenchymal Transitionen_US
dc.subjectBiomarkers, Tumoren_US
dc.titleEffect of Fluorouracil, Leucovorin, and Oxaliplatin With or Without Onartuzumab in HER2-Negative, MET-Positive Gastroesophageal Adenocarcinoma: The METGastric Randomized Clinical Trial.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1001/jamaoncol.2016.5580en_US
rioxxterms.licenseref.startdate2017-05en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfJAMA oncologyen_US
pubs.issue5en_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/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/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume3en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
dc.contributor.icrauthorCunningham, Daviden_US
dc.contributor.icrauthorMarsden,en_US


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