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dc.contributor.authorBundred, N
dc.contributor.authorPorta, N
dc.contributor.authorBrunt, AM
dc.contributor.authorCramer, A
dc.contributor.authorHanby, A
dc.contributor.authorShaaban, AM
dc.contributor.authorRakha, EA
dc.contributor.authorArmstrong, A
dc.contributor.authorCutress, RI
dc.contributor.authorDodwell, D
dc.contributor.authorEmson, MA
dc.contributor.authorEvans, A
dc.contributor.authorHartup, SM
dc.contributor.authorHorgan, K
dc.contributor.authorMiller, SE
dc.contributor.authorMcIntosh, SA
dc.contributor.authorMorden, JP
dc.contributor.authorNaik, J
dc.contributor.authorNarayanan, S
dc.contributor.authorOoi, J
dc.contributor.authorSkene, AI
dc.contributor.authorCameron, DA
dc.contributor.authorBliss, JM
dc.date.accessioned2022-03-28T09:15:36Z
dc.date.available2022-03-28T09:15:36Z
dc.date.issued2022-02-14
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2022en_US
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5050
dc.identifier.eissn1557-3265en_US
dc.identifier.eissn1557-3265
dc.identifier.eissn1557-3265
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-21-3177en_US
dc.identifier.doi10.1158/1078-0432.ccr-21-3177
dc.identifier.doi10.1158/1078-0432.ccr-21-3177
dc.identifier.doi10.1158/1078-0432.ccr-21-3177
dc.description.abstract<h4>Background</h4>EPHOS-B aimed to determine whether perioperative anti-HER2 therapy inhibited proliferation and/or increased apoptosis in HER2-positive breast cancer.<h4>Patients and methods</h4>This randomized phase II, two-part, multicenter trial included newly diagnosed women with HER2-positive invasive breast cancer due to undergo surgery. Patients were randomized to: part 1 (1:2:2), no treatment (control), trastuzumab or lapatinib; part 2 (1:1:2) control, trastuzumab, or lapatinib and trastuzumab combination. Treatment was given for 11 days presurgery. Coprimary endpoints were change in Ki67 and apoptosis between baseline and surgery tumor samples (biologic response: ≥30% change). Central pathology review scored residual cancer burden (RCB). Relapse-free survival (RFS) explored long-term effects.<h4>Results</h4>Between November 2010 and September 2015, 257 patients were randomized (part 1: control 22, trastuzumab 57, lapatinib 51; part 2: control 29, trastuzumab 32, combination 66). Ki67 response was evaluable for 223 patients: in part 1 Ki67 response occurred in 29/44 (66%) lapatinib versus 18/49 (37%) trastuzumab (<i>P</i> = 0.007) and 1/22 (5%) control (<i>P</i> < 0.0001); in part 2 in 36/49 (74%) combination versus 14/31 (45%) trastuzumab (<i>P</i> = 0.02) and 2/28 (7%) control (<i>P</i> < 0.0001). No significant increase in apoptosis after 11 days was seen in treatment groups. Six patients achieved complete pathologic response (pCR, RCB0) and 13 RCB1, all but two in the combination group. After 6 years median follow-up, 28 (11%) had recurrence and 19 (7%) died. No recurrences or deaths were observed among patients who achieved a pCR. Ki67% falls ≥50% associated with fewer recurrences (<i>P</i> = 0.002).<h4>Conclusions</h4>Early response after short duration anti-HER2 dual therapy identifies cancers dependent on the HER2 pathway providing a strategy for exploring risk-adapted individualized treatment de-escalation.en_US
dc.formatPrint-Electronicen_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleCombined Perioperative Lapatinib and Trastuzumab in Early HER2-Positive Breast Cancer Identifies Early Responders: Randomized UK EPHOS-B Trial Long-Term Results.en_US
dc.typeJournal Article
dcterms.dateAccepted2022-01-20
rioxxterms.versionAMen_US
rioxxterms.versionofrecord10.1158/1078-0432.ccr-21-3177en_US
rioxxterms.licenseref.startdate2022-02-14
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Researchen_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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit
pubs.publication-statusPublisheden_US
pubs.embargo.termsNot knownen_US
icr.researchteamClinical Trials & Statistics Unit
dc.contributor.icrauthorPorta, Nuriaen_US
dc.contributor.icrauthorBliss, Judithen_US


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