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dc.contributor.authorLoriot, Yen_US
dc.contributor.authorNecchi, Aen_US
dc.contributor.authorPark, SHen_US
dc.contributor.authorGarcia-Donas, Jen_US
dc.contributor.authorHuddart, Ren_US
dc.contributor.authorBurgess, Een_US
dc.contributor.authorFleming, Men_US
dc.contributor.authorRezazadeh, Aen_US
dc.contributor.authorMellado, Ben_US
dc.contributor.authorVarlamov, Sen_US
dc.contributor.authorJoshi, Men_US
dc.contributor.authorDuran, Ien_US
dc.contributor.authorTagawa, STen_US
dc.contributor.authorZakharia, Yen_US
dc.contributor.authorZhong, Ben_US
dc.contributor.authorStuyckens, Ken_US
dc.contributor.authorSantiago-Walker, Aen_US
dc.contributor.authorDe Porre, Pen_US
dc.contributor.authorO'Hagan, Aen_US
dc.contributor.authorAvadhani, Aen_US
dc.contributor.authorSiefker-Radtke, AOen_US
dc.contributor.authorBLC2001 Study Groupen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2019-08-20T10:02:27Z
dc.date.issued2019-07-25en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/31340094en_US
dc.identifier.citationN Engl J Med, 2019, 381 (4), pp. 338 - 348en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3325
dc.identifier.eissn1533-4406en_US
dc.identifier.doi10.1056/NEJMoa1817323en_US
dc.description.abstractBACKGROUND: Alterations in the gene encoding fibroblast growth factor receptor (FGFR) are common in urothelial carcinoma and may be associated with lower sensitivity to immune interventions. Erdafitinib, a tyrosine kinase inhibitor of FGFR1-4, has shown antitumor activity in preclinical models and in a phase 1 study involving patients with FGFR alterations. METHODS: In this open-label, phase 2 study, we enrolled patients who had locally advanced and unresectable or metastatic urothelial carcinoma with prespecified FGFR alterations. All the patients had a history of disease progression during or after at least one course of chemotherapy or within 12 months after neoadjuvant or adjuvant chemotherapy. Prior immunotherapy was allowed. We initially randomly assigned the patients to receive erdafitinib in either an intermittent or a continuous regimen in the dose-selection phase of the study. On the basis of an interim analysis, the starting dose was set at 8 mg per day in a continuous regimen (selected-regimen group), with provision for a pharmacodynamically guided dose escalation to 9 mg. The primary end point was the objective response rate. Key secondary end points included progression-free survival, duration of response, and overall survival. RESULTS: A total of 99 patients in the selected-regimen group received a median of five cycles of erdafitinib. Of these patients, 43% had received at least two previous courses of treatment, 79% had visceral metastases, and 53% had a creatinine clearance of less than 60 ml per minute. The rate of confirmed response to erdafitinib therapy was 40% (3% with a complete response and 37% with a partial response). Among the 22 patients who had undergone previous immunotherapy, the confirmed response rate was 59%. The median duration of progression-free survival was 5.5 months, and the median duration of overall survival was 13.8 months. Treatment-related adverse events of grade 3 or higher, which were managed mainly by dose adjustments, were reported in 46% of the patients; 13% of the patients discontinued treatment because of adverse events. There were no treatment-related deaths. CONCLUSIONS: The use of erdafitinib was associated with an objective tumor response in 40% of previously treated patients who had locally advanced and unresectable or metastatic urothelial carcinoma with FGFR alterations. Treatment-related grade 3 or higher adverse events were reported in nearly half the patients. (Funded by Janssen Research and Development; BLC2001 ClinicalTrials.gov number, NCT02365597.).en_US
dc.format.extent338 - 348en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectAged, 80 and overen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectHumansen_US
dc.subjectKaplan-Meier Estimateen_US
dc.subjectMiddle Ageden_US
dc.subjectMutationen_US
dc.subjectNeoplasm Metastasisen_US
dc.subjectProgression-Free Survivalen_US
dc.subjectProtein Kinase Inhibitorsen_US
dc.subjectProtein-Tyrosine Kinasesen_US
dc.subjectPyrazolesen_US
dc.subjectQuinoxalinesen_US
dc.subjectReceptors, Fibroblast Growth Factoren_US
dc.subjectTreatment Outcomeen_US
dc.subjectUrologic Neoplasmsen_US
dc.subjectUrotheliumen_US
dc.titleErdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1056/NEJMoa1817323en_US
rioxxterms.licenseref.startdate2019-07-25en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfN Engl J Meden_US
pubs.issue4en_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/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Clinical Academic Radiotherapy (Huddart)
pubs.publication-statusPublisheden_US
pubs.volume381en_US
pubs.embargo.termsNot knownen_US
icr.researchteamClinical Academic Radiotherapy (Huddart)en_US
dc.contributor.icrauthorHuddart, Roberten_US


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