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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorWardley, Andrew
dc.contributor.authorCortés Castan, Javier
dc.contributor.authorProvencher, Louise
dc.contributor.authorMiller, Kathy
dc.contributor.authorChien, A. Jo
dc.contributor.authorRugo, Hope
dc.date.accessioned2021-06-30T12:25:24Z
dc.date.available2021-06-30T12:25:24Z
dc.date.issued2021-05
dc.identifier.citationWardley A, Cortes J, Provencher L, Miller K, Chien AJ, Rugo HS, et al. The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer. Breast Cancer Res Treat. 2021 May;187:155-165.
dc.identifier.issn1573-7217
dc.identifier.urihttp://hdl.handle.net/11351/6111
dc.descriptionAndrogen receptor; HER2; Metastatic breast cancer
dc.description.abstractPurpose Androgen receptor (AR) expression occurs in up to 86% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers. In vitro, AR inhibitors enhance antitumor activity of trastuzumab, an anti-HER2 antibody, in trastuzumab-resistant HER2+ cell lines. This open-label, single-arm, phase II study evaluated the efficacy and safety of enzalutamide, an AR-signaling inhibitor, in patients with advanced HER2+ AR+ breast cancer previously treated with trastuzumab. Methods Eligible patients had measurable or non-measurable evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group status ≤ 1, no history of brain metastases, and previously received ≥ 1 anti-HER2 regimen for advanced disease. Patients received 160 mg oral enzalutamide daily and 6 mg/kg intravenous trastuzumab every 21 days until disease progression or unacceptable toxicity. Primary end point was clinical benefit rate at 24 weeks (CBR24); secondary end points included progression-free survival (PFS) and safety. Results Overall, 103 women were enrolled [median age 60 years (range 34–83)]; 62% had received ≥ 3 lines of prior anti-HER2 therapy. CBR24, comprising patients with confirmed partial responses (5%) and durable stable disease at 24 weeks (19%), was 24% in the efficacy evaluable set (n = 89). CBR24 did not seem related to AR-expression levels or hormone receptor status. Median PFS was 3.4 months (95% confidence interval 2.0–3.8). Overall, 97 (94%) patients experienced treatment-emergent adverse events (TEAEs), with fatigue most common (34%). Dyspnea (4%) and malignant neoplasm progression (3%) were the only TEAEs grade ≥ 3 reported in ≥ 3 patients. 22 patients (21%) reported serious TEAEs. Four patients (4%) experienced fatal, non-drug-related TEAEs. Conclusions Enzalutamide plus trastuzumab was well tolerated, and a subset of patients in this heavily pretreated population had durable disease control. Determination of biomarkers is needed to identify patients most likely to benefit from this combination.
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofseriesBreast Cancer Research and Treatment volume;187
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectMedicaments antineoplàstics - Eficàcia
dc.subjectMama - Càncer - Quimioteràpia
dc.subject.meshBreast Neoplasms
dc.subject.meshDrug Therapy, Combination
dc.subject.meshEfficacy
dc.titleThe efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1007/s10549-021-06109-7
dc.subject.decsneoplasias de la mama
dc.subject.decsfarmacoterapia combinada
dc.subject.decseficacia
dc.relation.publishversionhttps://link.springer.com/article/10.1007/s10549-021-06109-7
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Wardley A] NIHR Manchester Clinical Research Facility at The Christie NHS Foundation Trust and Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine, and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK. [Cortes J] Division of Breast Cancers and Gynecological Tumors, IOB Institute of Oncology, Quironsalud Group, Madrid and Barcelona, Spain. Breast Cancer & Melanoma Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Provencher L] Department of Surgery, Centre des Maladies du Sein, CHU de Québec-Université Laval, Québec, Canada. [Miller K] Indiana University Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, USA. [Chien AJ, Rugo HS] UCSF Comprehensive Cancer Center, University of California, San Francisco, USA
dc.identifier.pmid33591468
dc.identifier.wos000618588100002
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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