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dc.contributor.authorVan Cutsem, Een_US
dc.contributor.authorBang, Y-Jen_US
dc.contributor.authorMansoor, Wen_US
dc.contributor.authorPetty, RDen_US
dc.contributor.authorChao, Yen_US
dc.contributor.authorCunningham, Den_US
dc.contributor.authorFerry, DRen_US
dc.contributor.authorSmith, NRen_US
dc.contributor.authorFrewer, Pen_US
dc.contributor.authorRatnayake, Jen_US
dc.contributor.authorStockman, PKen_US
dc.contributor.authorKilgour, Een_US
dc.contributor.authorLanders, Den_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2018-02-16T15:33:18Z
dc.date.issued2017-06-01en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/29177434en_US
dc.identifier3859753en_US
dc.identifier.citationAnn Oncol, 2017, 28 (6), pp. 1316 - 1324en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1217
dc.identifier.eissn1569-8041en_US
dc.identifier.doi10.1093/annonc/mdx107en_US
dc.description.abstractBackground: Approximately 5%-10% of gastric cancers have a fibroblast growth factor receptor-2 (FGFR2) gene amplification. AZD4547 is a selective FGFR-1, 2, 3 tyrosine kinase inhibitor with potent preclinical activity in FGFR2 amplified gastric adenocarcinoma SNU16 and SGC083 xenograft models. The randomized phase II SHINE study (NCT01457846) investigated whether AZD4547 improves clinical outcome versus paclitaxel as second-line treatment in patients with advanced gastric adenocarcinoma displaying FGFR2 polysomy or gene amplification detected by fluorescence in situ hybridization. Patients and methods: Patients were randomized 3:2 (FGFR2 gene amplification) or 1:1 (FGFR2 polysomy) to AZD4547 or paclitaxel. Patients received AZD4547 80 mg twice daily, orally, on a 2 weeks on/1 week off schedule of a 21-day cycle or intravenous paclitaxel 80 mg/m2 administered weekly on days 1, 8, and 15 of a 28-day cycle. The primary end point was progression-free survival (PFS). Safety outcomes were assessed and an exploratory biomarker analysis was undertaken. Results: Of 71 patients randomized (AZD4547 n = 41, paclitaxel n = 30), 67 received study treatment (AZD4547 n = 40, paclitaxel n = 27). Among all randomized patients, median PFS was 1.8 months with AZD4547 and 3.5 months with paclitaxel (one-sided P = 0.9581); median follow-up duration for PFS was 1.77 and 2.12 months, respectively. The incidence of adverse events was similar in both treatment arms. Exploratory biomarker analyses revealed marked intratumor heterogeneity of FGFR2 amplification and poor concordance between amplification/polysomy and FGFR2 mRNA expression. Conclusions: AZD4547 did not significantly improve PFS versus paclitaxel in gastric cancer FGFR2 amplification/polysomy patients. Considerable intratumor heterogeneity for FGFR2 gene amplification and poor concordance between FGFR2 amplification/polysomy and FGFR2 expression indicates the need for alternative predictive biomarker testing. AZD4547 was generally well tolerated.en_US
dc.format.extent1316 - 1324en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectAZD4547en_US
dc.subjectclinical efficacyen_US
dc.subjectfibroblast growth factor receptoren_US
dc.subjectfluorescence in situ hybridizationen_US
dc.subjectgastric canceren_US
dc.subjectAdenocarcinomaen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectBenzamidesen_US
dc.subjectCell Line, Tumoren_US
dc.subjectDisease-Free Survivalen_US
dc.subjectGene Amplificationen_US
dc.subjectHumansen_US
dc.subjectPaclitaxelen_US
dc.subjectPiperazinesen_US
dc.subjectPyrazolesen_US
dc.subjectReceptor, Fibroblast Growth Factor, Type 2en_US
dc.subjectStomach Neoplasmsen_US
dc.titleA randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1093/annonc/mdx107en_US
rioxxterms.licenseref.startdate2017-06-01en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfAnn Oncolen_US
pubs.issue6en_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.volume28en_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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