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dc.contributor.authorLoibl, Sen_US
dc.contributor.authorTurner, NCen_US
dc.contributor.authorRo, Jen_US
dc.contributor.authorCristofanilli, Men_US
dc.contributor.authorIwata, Hen_US
dc.contributor.authorIm, S-Aen_US
dc.contributor.authorMasuda, Nen_US
dc.contributor.authorLoi, Sen_US
dc.contributor.authorAndré, Fen_US
dc.contributor.authorHarbeck, Nen_US
dc.contributor.authorVerma, Sen_US
dc.contributor.authorFolkerd, Een_US
dc.contributor.authorPuyana Theall, Ken_US
dc.contributor.authorHoffman, Jen_US
dc.contributor.authorZhang, Ken_US
dc.contributor.authorBartlett, CHen_US
dc.contributor.authorDowsett, Men_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2017-11-24T11:04:23Z
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28652278en_US
dc.identifiertheoncologist.2017-0072en_US
dc.identifier.citationOncologist, 22 (9), pp. 1028 - 1038en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/946
dc.identifier.eissn1549-490Xen_US
dc.identifier.doi10.1634/theoncologist.2017-0072en_US
dc.description.abstractBACKGROUND: The efficacy and safety of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, combined with fulvestrant and goserelin was assessed in premenopausal women with advanced breast cancer (ABC) who had progressed on prior endocrine therapy (ET). PATIENTS AND METHODS: One hundred eight premenopausal endocrine-refractory women ≥18 years with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) ABC were among 521 women randomized 2:1 (347:174) to fulvestrant (500 mg) ± goserelin with either palbociclib (125 mg/day orally, 3 weeks on, 1 week off) or placebo. This analysis assessed whether the overall tolerable safety profile and significant progression-free survival (PFS) improvement extended to premenopausal women. Potential drug-drug interactions (DDIs) and ovarian suppression with goserelin were assessed via plasma pharmacokinetics and biochemical analyses, respectively. (ClinicalTrials.gov identifier: NCT01942135) RESULTS: Median PFS for premenopausal women in the palbociclib (n = 72) versus placebo arm (n = 36) was 9.5 versus 5.6 months, respectively (hazard ratio, 0.50, 95% confidence interval: 0.29-0.87), and consistent with the significant PFS improvement in the same arms for postmenopausal women. Any-grade and grade ≤3 neutropenia, leukopenia, and infections were among the most frequent adverse events reported in the palbociclib arm with concurrent goserelin administration. Hormone concentrations were similar between treatment arms and confirmed sustained ovarian suppression. Clinically relevant DDIs were not observed. CONCLUSION: Palbociclib combined with fulvestrant and goserelin was an effective and well-tolerated treatment for premenopausal women with prior endocrine-resistant HR+/HER2- ABC. Inclusion of both premenopausal and postmenopausal women in pivotal combination ET trials facilitates access to novel drugs for young women and should be considered as a new standard for clinical trial design. IMPLICATIONS FOR PRACTICE: PALOMA-3, the first registrational study to include premenopausal women in a trial investigating a CDK4/6 inhibitor combined with endocrine therapy, has the largest premenopausal cohort reported in an endocrine-resistant setting. In pretreated premenopausal women with hormone receptor-positive advanced breast cancer, palbociclib plus fulvestrant and goserelin (luteinizing hormone-releasing hormone [LHRH] agonist) treatment almost doubled median progression-free survival (PFS) and significantly increased the objective response rate versus endocrine monotherapy, achieving results comparable to those reported for chemotherapy without apparently interfering with LHRH agonist-induced ovarian suppression. The significant PFS gain and tolerable safety profile strongly support use of this regimen in premenopausal women with endocrine-resistant disease who could possibly delay chemotherapy.en_US
dc.format.extent1028 - 1038en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
dc.subjectBreast canceren_US
dc.subjectFulvestranten_US
dc.subjectGoserelinen_US
dc.subjectNeoplasm metastasisen_US
dc.subjectPalbocicliben_US
dc.subjectPremenopausalen_US
dc.subjectAdulten_US
dc.subjectAntineoplastic Combined Chemotherapy Protocolsen_US
dc.subjectBreast Neoplasmsen_US
dc.subjectCyclin-Dependent Kinase 4en_US
dc.subjectCyclin-Dependent Kinase 6en_US
dc.subjectDisease-Free Survivalen_US
dc.subjectDrug Interactionsen_US
dc.subjectDrug Resistance, Neoplasmen_US
dc.subjectEstradiolen_US
dc.subjectFemaleen_US
dc.subjectGonadotropin-Releasing Hormoneen_US
dc.subjectGoserelinen_US
dc.subjectHumansen_US
dc.subjectMiddle Ageden_US
dc.subjectPiperazinesen_US
dc.subjectPremenopauseen_US
dc.subjectProtein Kinase Inhibitorsen_US
dc.subjectPyridinesen_US
dc.subjectReceptor, ErbB-2en_US
dc.subjectReceptors, Estrogenen_US
dc.subjectReceptors, Progesteroneen_US
dc.subjectTreatment Outcomeen_US
dc.titlePalbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-03-23en_US
rioxxterms.funderThe Institute of Cancer Researchen_US
rioxxterms.identifier.projectUnspecifieden_US
rioxxterms.versionofrecord10.1634/theoncologist.2017-0072en_US
rioxxterms.licenseref.startdate2017-03-23en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfOncologisten_US
pubs.issue9en_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/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume22en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMolecular Oncologyen_US
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorFolkerd, Elizabethen_US
dc.contributor.icrauthorTurner, Nicholasen_US
dc.contributor.icrauthorDowsett, Mitchen_US
dc.contributor.icrauthorMarsden,en_US
rioxxterms.funder.project354849bd-c553-4e22-868c-8c503e124155en_US


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