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dc.contributor.authorCoombes, RC
dc.contributor.authorBadman, PD
dc.contributor.authorLozano-Kuehne, JP
dc.contributor.authorLiu, X
dc.contributor.authorMacpherson, IR
dc.contributor.authorZubairi, I
dc.contributor.authorBaird, RD
dc.contributor.authorRosenfeld, N
dc.contributor.authorGarcia-Corbacho, J
dc.contributor.authorCresti, N
dc.contributor.authorPlummer, R
dc.contributor.authorArmstrong, A
dc.contributor.authorAllerton, R
dc.contributor.authorLanders, D
dc.contributor.authorNicholas, H
dc.contributor.authorMcLellan, L
dc.contributor.authorLim, A
dc.contributor.authorMouliere, F
dc.contributor.authorPardo, OE
dc.contributor.authorFerguson, V
dc.contributor.authorSeckl, MJ
dc.date.accessioned2022-06-24T23:30:41Z
dc.date.available2022-06-24T23:30:41Z
dc.date.issued2022-06-10
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338357
dc.description.abstractWe conducted a phase IIa, multi-centre, open label, single arm study (RADICAL; NCT01791985) of AZD4547 (a potent and selective inhibitor of Fibroblast Growth Factor Receptor (FGFR)-1, 2 and 3 receptor tyrosine kinases) administered with anastrozole or letrozole in estrogen receptor positive metastatic breast cancer patients who had become resistant to aromatase inhibitors. After a safety run-in study to assess safety and tolerability, we recruited 52 patients. The primary endpoint was change in tumour size at 12 weeks, and secondary endpoints were to assess response at 6 weeks, 20 weeks and every 8 weeks thereafter and tolerability of the combined treatment. Two partial responses (PR) and 19 stable disease (SD) patients were observed at the 12-week time point. At 28 weeks, according to centrally reviewed Response Evaluation Criteria in Solid Tumours (RECIST) criteria, five PR and 8 SD patients were observed in 50 assessable cases. Overall, objective response rate (5 PR) was of 10%, meeting the pre-specified endpoint. Fourteen patients discontinued due to adverse events. Eleven patients had retinal pigment epithelial detachments which was asymptomatic and reversible in all but one patient. Exploratory ribonucleic acid sequencing (RNA-Seq) analysis was done on patients' samples: 6 differentially-expressed-genes could distinguish those who benefited from the addition of AZD4547.
dc.format.mediumElectronic
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectBenzamides
dc.subjectBreast Neoplasms
dc.subjectFemale
dc.subjectHumans
dc.subjectPiperazines
dc.subjectPyrazoles
dc.titleResults of the phase IIa RADICAL trial of the FGFR inhibitor AZD4547 in endocrine resistant breast cancer.
dc.typeArticle
dc.publisher.departmentDepartment of Oncology
dc.publisher.departmentCancer Research Uk Cambridge Institute
dc.date.updated2022-06-23T22:03:04Z
prism.issueIdentifier1
prism.number3246
prism.publicationDate2022
prism.publicationNameNat Commun
prism.startingPage3246
prism.volume13
dc.identifier.doi10.17863/CAM.85766
dcterms.dateAccepted2022-05-12
rioxxterms.versionofrecord10.1038/s41467-022-30666-0
rioxxterms.versionVoR
dc.contributor.orcidCoombes, RC [0000-0002-4811-1100]
dc.contributor.orcidBadman, PD [0000-0002-0337-3190]
dc.contributor.orcidLozano-Kuehne, JP [0000-0002-7372-0725]
dc.contributor.orcidMacpherson, IR [0000-0003-4295-8885]
dc.contributor.orcidBaird, RD [0000-0001-7071-6483]
dc.contributor.orcidRosenfeld, N [0000-0002-2825-4788]
dc.contributor.orcidGarcia-Corbacho, J [0000-0002-6109-8449]
dc.contributor.orcidCresti, N [0000-0002-0495-4472]
dc.contributor.orcidLanders, D [0000-0001-8376-9779]
dc.contributor.orcidMouliere, F [0000-0001-7043-0514]
dc.contributor.orcidPardo, OE [0000-0003-2223-1435]
dc.contributor.orcidSeckl, MJ [0000-0003-4078-2599]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Review
cam.issuedOnline2022-06-10
cam.depositDate2022-06-23
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International