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dc.contributor.authorFuchs, CS
dc.contributor.authorTabernero, J
dc.contributor.authorTomášek, J
dc.contributor.authorChau, I
dc.contributor.authorMelichar, B
dc.contributor.authorSafran, H
dc.contributor.authorTehfe, MA
dc.contributor.authorFilip, D
dc.contributor.authorTopuzov, E
dc.contributor.authorSchlittler, L
dc.contributor.authorUdrea, AA
dc.contributor.authorCampbell, W
dc.contributor.authorBrincat, S
dc.contributor.authorEmig, M
dc.contributor.authorMelemed, SA
dc.contributor.authorHozak, RR
dc.contributor.authorFerry, D
dc.contributor.authorCaldwell, CW
dc.contributor.authorAjani, JA
dc.date.accessioned2017-04-03T09:34:57Z
dc.date.issued2016-10
dc.identifier.citationBritish journal of cancer, 2016, 115 (8), pp. 974 - 982
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/539
dc.identifier.eissn1532-1827
dc.identifier.doi10.1038/bjc.2016.293
dc.description.abstractBackground Angiogenesis inhibition is an important strategy for cancer treatment. Ramucirumab, a human IgG1 monoclonal antibody that targets VEGF receptor 2 (VEGFR2), inhibits VEGF-A, -C, -D binding and endothelial cell proliferation. To attempt to identify prognostic and predictive biomarkers, retrospective analyses were used to assess tumour (HER2, VEGFR2) and serum (VEGF-C and -D, and soluble (s) VEGFR1 and 3) biomarkers in phase 3 REGARD patients with metastatic gastric/gastroesophageal junction carcinoma.Methods A total of 152 out of 355 (43%) patients randomised to ramucirumab or placebo had ⩾1 evaluable biomarker result using VEGFR2 immunohistochemistry or HER2, immunohistochemistry or FISH, of blinded baseline tumour tissue samples. Serum samples (32 patients, 9%) were assayed for VEGF-C and -D, and sVEGFR1 and 3.Results None of the biomarkers tested were associated with ramucirumab efficacy at a level of statistical significance. High VEGFR2 endothelial expression was associated with a non-significant prognostic trend toward shorter progression-free survival (high vs low HR=1.65, 95% CI=0.84,3.23). Treatment with ramucirumab was associated with a trend toward improved survival in both high (HR=0.69, 95% CI=0.38, 1.22) and low (HR=0.73, 95% CI=0.42, 1.26) VEGFR2 subgroups. The benefit associated with ramucirumab did not appear to differ by tumoural HER2 expression.Conclusions REGARD exploratory analyses did not identify a strong potentially predictive biomarker of ramucirumab efficacy; however, statistical power was limited.
dc.formatPrint-Electronic
dc.format.extent974 - 982
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectEsophagogastric Junction
dc.subjectHumans
dc.subjectAdenocarcinoma
dc.subjectStomach Neoplasms
dc.subjectReceptor, erbB-2
dc.subjectReceptors, Vascular Endothelial Growth Factor
dc.subjectVascular Endothelial Growth Factor Receptor-2
dc.subjectAngiogenesis Inhibitors
dc.subjectVascular Endothelial Growth Factors
dc.subjectNeoplasm Proteins
dc.subjectAntineoplastic Agents
dc.subjectAntibodies, Monoclonal
dc.subjectDisease-Free Survival
dc.subjectRetrospective Studies
dc.subjectSingle-Blind Method
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectMulticenter Studies as Topic
dc.subjectRandomized Controlled Trials as Topic
dc.subjectClinical Trials, Phase III as Topic
dc.subjectKaplan-Meier Estimate
dc.subjectAntibodies, Monoclonal, Humanized
dc.subjectBiomarkers, Tumor
dc.titleBiomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab.
dc.typeJournal Article
dcterms.dateAccepted2016-08-16
rioxxterms.versionofrecord10.1038/bjc.2016.293
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-sa/4.0
rioxxterms.licenseref.startdate2016-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBritish journal of cancer
pubs.issue8
pubs.notes12 months
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume115
pubs.embargo.terms12 months
dc.contributor.icrauthorChau, Ianen


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