Show simple item record

 
dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorGavilá Gregori, Joaquín
dc.contributor.authorAntunes de Melo Oliveira, Ana Mafalda
dc.contributor.authorPascual, Tomás
dc.contributor.authorPérez García, José
dc.contributor.authorGonzàlez, Xavier
dc.contributor.authorCanes, Jordi
dc.date.accessioned2019-02-22T11:59:06Z
dc.date.available2019-02-22T11:59:06Z
dc.date.issued2019-01-09
dc.identifier.citationGavilá J, Oliveira M, Pascual T, Perez-Garcia J, Gonzàlez X, Canes J, et al. Safety, activity, and molecular heterogeneity following neoadjuvant non-pegylated liposomal doxorubicin, paclitaxel, trastuzumab, and pertuzumab in HER2-positive breast cancer (Opti-HER HEART): an open-label, single-group, multicenter, phase 2 trial. BMC Med. 2019;17(1):8.
dc.identifier.issn1741-7015
dc.identifier.urihttp://hdl.handle.net/11351/3808
dc.descriptionBreast cancer; HER2; Neoadjuvant
dc.description.abstractBackground The Opti-HER HEART trial aimed to optimize activity while minimizing cardiac risk by combining trastuzumab, pertuzumab, and paclitaxel with non-pegylated liposomal doxorubicin in the treatment of HER2-positive early breast cancer. Methods Patients with stage II–IIIB HER2-positive breast cancer received neoadjuvant trastuzumab, pertuzumab, paclitaxel, and a non-pegylated liposomal doxorubicin every three weeks for six cycles. The primary endpoint was cardiac safety during neoadjuvant therapy. Type A (symptomatic congestive heart failure) and B (asymptomatic reduction of left ventricular ejection fraction) cardiac events were evaluated. Secondary endpoints included the evaluation of the pathological complete response (pCR) rate and overall response rate, among others. As an ad-hoc exploratory analysis, the expression of 55 breast cancer-related genes, including the PAM50 genes, was measured in 58 baseline tumor samples and 60 surgical specimens. Results Eighty-three patients were recruited. The incidence of cardiac events during neoadjuvant treatment was 2.4%. No type A cardiac event was observed. The overall pCR rate was 56.6% (95% confidence interval (CI) 45.3–67.5%). The HER2-enriched subtype, which represented 52.0% of all baseline samples, was associated with a higher pCR rate compared to non-HER2-enriched tumors (83.3% vs. 46.3%; odds ratio 5.76, 95% CI 1.71–19.42). The association of subtype with pCR was independent of known clinicopathological variables, including hormone receptor status. Compared to baseline samples, surgical specimens showed a significant downregulation of proliferation-related genes (MKI67 and CCNB1) and ERBB2 levels, and a significant upregulation of luminal-related (ESR1 and PGR) and immune (CD8A) genes. Conclusions The combination of dual HER2 blockade with trastuzumab and pertuzumab with paclitaxel and non-pegylated liposomal doxorubicin is associated with a low rate of cardiac events. The HER2-enriched subtype is associated with a high rate of pCR.
dc.language.isoeng
dc.publisherBMC
dc.relation.ispartofseriesBMC Medicine;17(1)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceScientia
dc.subjectMama - Càncer
dc.subjectCàncer - Quimioteràpia - Complicacions
dc.subjectAssaigs clínics
dc.subject.meshBreast Neoplasms
dc.subject.mesh/drug therapy
dc.subject.meshNeoadjuvant Therapy
dc.subject.mesh/adverse effects
dc.subject.meshClinical Trial
dc.titleSafety, activity, and molecular heterogeneity following neoadjuvant non-pegylated liposomal doxorubicin, paclitaxel, trastuzumab, and pertuzumab in HER2-positive breast cancer (Opti-HER HEART): an open-label, single-group, multicenter, phase 2 trial
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1186/s12916-018-1233-1
dc.subject.decsneoplasias de la mama
dc.subject.decs/tratamiento farmacológico
dc.subject.decstratamiento neoadyuvante
dc.subject.decs/efectos adversos
dc.subject.decsensayo clínico
dc.relation.publishversionhttps://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-018-1233-1
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Gavilá J] Fundación Instituto Valenciano de Oncología, Valencia, Spain. [Oliveira M] Hospital Universitari Vall d'Hebron, Barcelona, Spain. Vall d'Hebron Institut d'Oncologia, Barcelona, Spain. [Pascual T] August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain. Hospital Clínic, Barcelona, Spain. SOLTI Breast Cancer Research Group, Barcelona, Spain. [Perez-Garcia J] Hospital Universitari Vall d'Hebron, Barcelona, Spain. Vall d'Hebron Institut d'Oncologia, Barcelona, Spain. Instituto Oncológico Baselga, Hospital Quirón, Barcelona, Spain. [Gonzàlez X] SOLTI Breast Cancer Research Group, Barcelona, Spain. Institut Oncològic Rosell, Hospital General Catalunya, Barcelona, Spain. [Canes J] SOLTI Breast Cancer Research Group, Barcelona, Spain.
dc.identifier.pmid30621698
dc.identifier.wosWOS:000455212100001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record