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dc.contributor.authorOkines, A
dc.contributor.authorIrfan, T
dc.contributor.authorKhabra, K
dc.contributor.authorSmith, I
dc.contributor.authorO'Brien, M
dc.contributor.authorParton, M
dc.contributor.authorNoble, J
dc.contributor.authorStanway, S
dc.contributor.authorSomaiah, N
dc.contributor.authorRing, A
dc.contributor.authorJohnston, S
dc.contributor.authorTurner, N
dc.date.accessioned2017-09-18T09:08:44Z
dc.date.issued2018-05-01
dc.identifier.citationThe breast journal, 2018, 24 (3), pp. 253 - 259
dc.identifier.issn1075-122X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/827
dc.identifier.eissn1524-4741
dc.identifier.doi10.1111/tbj.12906
dc.description.abstractAdo-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that does not cross an intact blood-brain barrier. In the EMILIA trial of T-DM1 vs capecitabine/lapatinib for HER2 positive advanced breast cancer, all patients had baseline brain imaging, and 9/450 (2%) of patients with negative baseline imaging developed new brain disease during T-DM1. We assessed the frequency of brain progression in clinical practice, without routine baseline imaging. We undertook a retrospective study of all patients treated with T-DM1 at the Royal Marsden Hospital from 2011 to 2016. Data collected included baseline characteristics, previous treatment for advanced breast cancer, sites of metastatic disease, duration of T-DM1, sites of progression, and treatment of CNS progression. Fifty-five patients were identified who had received a median of two prior lines of treatment (range 0-5). All were HER2 positive; 45 patients had IHC 3+ tumors and 10 were ISH positive. Patients received a median of 12 cycles of T-DM1 (range 1-34), and six remain on treatment at the time of analysis. Before commencing T-DM1, 16/55 (29%) had known brain metastases (treated with whole brain [9] stereotactic radiotherapy [6] or both [1]). Brain was the first site of progression in 56% (9/16) patients, with a median time to brain progression of 9.9 months (95% CI 3.9-12.2). In patients without known baseline brain metastases, 17.9% (7/39) developed new symptomatic brain disease during T-DM1, after a median of 7.5 months (95%CI 3.8-9.6). Brain progression was isolated, with control of extra-cranial disease in 4/7 patients. Only one patient was suitable for stereotactic radiotherapy. Median time to extra-cranial progression in all patients was 11.5 months (95% CI 9.1-17.7), and median OS in all patients was 17.8 months (95% CI 14.2-22). In patients not screened for brain metastases at baseline, the brain was the first site of progression in a significant proportion. Baseline brain imaging may have a role in standard practice for patients commencing T-DM1 therapy.
dc.formatPrint-Electronic
dc.format.extent253 - 259
dc.languageeng
dc.language.isoeng
dc.publisherWILEY
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectBrain Neoplasms
dc.subjectCerebral Hemorrhage
dc.subjectMaytansine
dc.subjectReceptor, erbB-2
dc.subjectTreatment Outcome
dc.subjectRetrospective Studies
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectTrastuzumab
dc.subjectAntineoplastic Agents, Immunological
dc.subjectAdo-Trastuzumab Emtansine
dc.titleDevelopment and responses of brain metastases during treatment with trastuzumab emtansine (T-DM1) for HER2 positive advanced breast cancer: A single institution experience.
dc.typeJournal Article
dcterms.dateAccepted2017-01-23
rioxxterms.funderThe Institute of Cancer Research
rioxxterms.identifier.projectUnspecified
rioxxterms.versionofrecord10.1111/tbj.12906
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-05
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfThe breast journal
pubs.issue3
pubs.notesNot known
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/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrine Therapy Resistance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology
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/ICR Divisions/Clinical Studies/Treatment of thoracic tumours
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Treatment of thoracic tumours/Treatment of thoracic tumours (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Breast Radiobiology
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/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrine Therapy Resistance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology
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/ICR Divisions/Clinical Studies/Treatment of thoracic tumours
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Treatment of thoracic tumours/Treatment of thoracic tumours (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Breast Radiobiology
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume24
pubs.embargo.termsNot known
icr.researchteamEndocrine Therapy Resistance
icr.researchteamMolecular Oncology
icr.researchteamMedicine (RMH Smith Cunningham)
icr.researchteamTreatment of thoracic tumours
icr.researchteamTranslational Breast Radiobiology
dc.contributor.icrauthorSomaiah, Navita
dc.contributor.icrauthorTurner, Nicholas


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