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dc.contributor.authorCristofanilli, M
dc.contributor.authorDeMichele, A
dc.contributor.authorGiorgetti, C
dc.contributor.authorTurner, NC
dc.contributor.authorSlamon, DJ
dc.contributor.authorIm, S-A
dc.contributor.authorMasuda, N
dc.contributor.authorVerma, S
dc.contributor.authorLoi, S
dc.contributor.authorColleoni, M
dc.contributor.authorTheall, KP
dc.contributor.authorHuang, X
dc.contributor.authorLiu, Y
dc.contributor.authorBartlett, CH
dc.date.accessioned2018-11-14T11:05:35Z
dc.date.issued2018-11
dc.identifier.citationEuropean journal of cancer (Oxford, England : 1990), 2018, 104 pp. 21 - 31
dc.identifier.issn0959-8049
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2933
dc.identifier.eissn1879-0852
dc.identifier.doi10.1016/j.ejca.2018.08.011
dc.description.abstractBackground The addition of palbociclib to fulvestrant improved clinical outcomes over placebo-fulvestrant in endocrine-pretreated metastatic breast cancer (MBC) patients in PALOMA-3. Here, we examined factors predictive of long-term benefit.Methods Premenopausal-peri/postmenopausal patients with endocrine-resistant, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative MBC were randomised 2:1 to fulvestrant (500 mg) and either palbociclib (125 mg/d; 3/1 schedule; n = 347) or placebo (n = 174). Baseline characteristics, mutation status and HR expression levels were compared in patients with and without prolonged benefit (treatment duration ≥18 months).Results By August 2016, 100 patients (29%) on palbociclib-fulvestrant and 26 (15%) on placebo-fulvestrant demonstrated prolonged benefit, with long-term responders in both arms sharing common clinical characteristics. They usually had less disease burden at baseline versus those treated <18 months, such as having one disease site (40% vs 29% on palbociclib-fulvestrant and 69% vs 29% on placebo-fulvestrant), bone-only disease (32% vs 22% and 46% vs 17%) and were less heavily pretreated (69% vs 56% and 73% vs 60% had ≤2 prior therapies). Baseline tumour ESR1 and PIK3CA mutation rates were lower among long-term responders in both arms; median oestrogen receptor H-scores were similar, whereas progesterone receptor H-scores were higher among long-term responders.Conclusions This exploratory analysis demonstrates that some patients with endocrine-resistant MBC derive significant and prolonged benefit when treated with palbociclib-fulvestrant, with fewer patients experiencing similar efficacy with placebo-fulvestrant. The current analysis did not identify specific molecular or clinical factors prognostic of long-term benefit with palbociclib-fulvestrant (ClinicalTrials.gov, NCT01942135).
dc.formatPrint-Electronic
dc.format.extent21 - 31
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectCarcinoma
dc.subjectBreast Neoplasms
dc.subjectNeoplasms, Hormone-Dependent
dc.subjectPiperazines
dc.subjectPyridines
dc.subjectProgesterone
dc.subjectReceptor, erbB-2
dc.subjectNeoplasm Proteins
dc.subjectReceptors, Estrogen
dc.subjectReceptors, Progesterone
dc.subjectAntineoplastic Agents, Hormonal
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectEstrogens
dc.subjectDisease-Free Survival
dc.subjectProportional Hazards Models
dc.subjectFollow-Up Studies
dc.subjectDouble-Blind Method
dc.subjectDrug Resistance, Neoplasm
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectKaplan-Meier Estimate
dc.subjectFulvestrant
dc.subjectProgression-Free Survival
dc.titlePredictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in PALOMA-3.
dc.typeJournal Article
dcterms.dateAccepted2018-08-16
rioxxterms.versionofrecord10.1016/j.ejca.2018.08.011
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEuropean journal of cancer (Oxford, England : 1990)
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/Molecular Oncology
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/Molecular Oncology
pubs.publication-statusPublished
pubs.volume104en_US
pubs.embargo.termsNot known
icr.researchteamMolecular Oncologyen_US
dc.contributor.icrauthorTurner, Nicholasen


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