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dc.contributor.authorTurner, NC
dc.contributor.authorSwift, C
dc.contributor.authorKilburn, L
dc.contributor.authorFribbens, C
dc.contributor.authorBeaney, M
dc.contributor.authorGarcia-Murillas, I
dc.contributor.authorBudzar, AU
dc.contributor.authorRobertson, JFR
dc.contributor.authorGradishar, W
dc.contributor.authorPiccart, M
dc.contributor.authorSchiavon, G
dc.contributor.authorBliss, JM
dc.contributor.authorDowsett, M
dc.contributor.authorJohnston, SRD
dc.contributor.authorChia, SK
dc.date.accessioned2020-07-06T11:14:37Z
dc.date.issued2020-10
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2020, 26 (19), pp. 5172 - 5177
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3804
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-20-0224
dc.description.abstractPurpose <i>ESR1</i> mutations are acquired frequently in hormone receptor-positive metastatic breast cancer after prior aromatase inhibitors. We assessed the clinical utility of baseline <i>ESR1</i> circulating tumor DNA (ctDNA) analysis in the two phase III randomized trials of fulvestrant versus exemestane.Experimental design The phase III EFECT and SoFEA trials randomized patients with hormone receptor-positive metastatic breast cancer who had progressed on prior nonsteroidal aromatase inhibitor therapy, between fulvestrant 250 mg and exemestane. Baseline serum samples from 227 patients in EFECT, and baseline plasma from 161 patients in SoFEA, were analyzed for <i>ESR1</i> mutations by digital PCR. The primary objectives were to assess the impact of <i>ESR1</i> mutation status on progression-free (PFS) and overall survival (OS) in a combined analysis of both studies.Results <i>ESR1</i> mutations were detected in 30% (151/383) baseline samples. In patients with <i>ESR1</i> mutation detected, PFS was 2.4 months [95% confidence interval (CI), 2.0-2.6] on exemestane and 3.9 months (95% CI, 3.0-6.0) on fulvestrant [hazard ratio (HR), 0.59; 95% CI, 0.39-0.89; <i>P</i> = 0.01). In patients without <i>ESR1</i> mutations detected, PFS was 4.8 months (95% CI, 3.7-6.2) on exemestane and 4.1 months (95% CI, 3.6-5.5) on fulvestrant (HR, 1.05; 95% CI, 0.81-1.37; <i>P</i> = 0.69). There was an interaction between <i>ESR1</i> mutation and treatment (<i>P</i> = 0.02). Patients with <i>ESR1</i> mutation detected had 1-year OS of 62% (95% CI, 45%-75%) on exemestane and 80% (95% CI, 68%-87%) on fulvestrant (<i>P</i> = 0.04; restricted mean survival analysis). Patients without <i>ESR1</i> mutations detected had 1-year OS of 79% (95% CI, 71%-85%) on exemestane and 81% (95% CI, 74%-87%) on fulvestrant (<i>P</i> = 0.69).Conclusions Detection of <i>ESR1</i> mutations in baseline ctDNA is associated with inferior PFS and OS in patients treated with exemestane versus fulvestrant.
dc.formatPrint-Electronic
dc.format.extent5172 - 5177
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.title<i>ESR1</i> Mutations and Overall Survival on Fulvestrant versus Exemestane in Advanced Hormone Receptor-Positive Breast Cancer: A Combined Analysis of the Phase III SoFEA and EFECT Trials.
dc.typeJournal Article
dcterms.dateAccepted2020-06-11
rioxxterms.versionofrecord10.1158/1078-0432.ccr-20-0224
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Research
pubs.issue19
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/Endocrinology
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/Clinical Trials & Statistics Unit
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
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit
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.publication-statusPublished
pubs.volume26en_US
pubs.embargo.termsNot known
icr.researchteamMolecular Oncologyen_US
icr.researchteamClinical Trials & Statistics Uniten_US
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorKilburn, Lucyen
dc.contributor.icrauthorGarcia-Murillas, Isaacen
dc.contributor.icrauthorTurner, Nicholasen
dc.contributor.icrauthorBliss, Judithen
dc.contributor.icrauthorDowsett, Mitchen


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