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Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study

PURPOSE: HER2-targeted therapies have substantially improved the outcome of patients with breast cancer, however, they can be associated with cardiac toxicity. Guidelines recommend holding HER2-targeted therapies until resolution of cardiac dysfunction. SAFE-HEaRt is the first trial that prospective...

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Autores principales: Lynce, F., Barac, A., Geng, X., Dang, C., Yu, A. F., Smith, K. L., Gallagher, C., Pohlmann, P. R., Nunes, R., Herbolsheimer, P., Warren, R., Srichai, M. B., Hofmeyer, M., Cunningham, A., Timothee, P., Asch, F. M., Shajahan-Haq, A., Tan, M. T., Isaacs, C., Swain, S. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534513/
https://www.ncbi.nlm.nih.gov/pubmed/30852761
http://dx.doi.org/10.1007/s10549-019-05191-2
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author Lynce, F.
Barac, A.
Geng, X.
Dang, C.
Yu, A. F.
Smith, K. L.
Gallagher, C.
Pohlmann, P. R.
Nunes, R.
Herbolsheimer, P.
Warren, R.
Srichai, M. B.
Hofmeyer, M.
Cunningham, A.
Timothee, P.
Asch, F. M.
Shajahan-Haq, A.
Tan, M. T.
Isaacs, C.
Swain, S. M.
author_facet Lynce, F.
Barac, A.
Geng, X.
Dang, C.
Yu, A. F.
Smith, K. L.
Gallagher, C.
Pohlmann, P. R.
Nunes, R.
Herbolsheimer, P.
Warren, R.
Srichai, M. B.
Hofmeyer, M.
Cunningham, A.
Timothee, P.
Asch, F. M.
Shajahan-Haq, A.
Tan, M. T.
Isaacs, C.
Swain, S. M.
author_sort Lynce, F.
collection PubMed
description PURPOSE: HER2-targeted therapies have substantially improved the outcome of patients with breast cancer, however, they can be associated with cardiac toxicity. Guidelines recommend holding HER2-targeted therapies until resolution of cardiac dysfunction. SAFE-HEaRt is the first trial that prospectively tests whether these therapies can be safely administered without interruptions in patients with cardiac dysfunction. METHODS: Patients with stage I–IV HER2-positive breast cancer candidates for trastuzumab, pertuzumab or ado-trastuzumab emtansine (TDM-1), with left ventricular ejection fraction (LVEF) 40–49% and no symptoms of heart failure (HF) were enrolled. All patients underwent cardiology visits, serial echocardiograms and received beta blockers and ACE inhibitors unless contraindicated. The primary endpoint was completion of the planned HER2-targeted therapies without developing either a cardiac event (CE) defined as HF, myocardial infarction, arrhythmia or cardiac death or significant asymptomatic worsening of LVEF. The study was considered successful if planned oncology therapy completion rate was at least 30%. RESULTS: Of 31 enrolled patients, 30 were evaluable. Fifteen patients were treated with trastuzumab, 14 with trastuzumab and pertuzumab, and 2 with TDM-1. Mean LVEF was 45% at baseline and 46% at the end of treatment. Twenty-seven patients (90%) completed the planned HER2-targeted therapies. Two patients experienced a CE and 1 had an asymptomatic worsening of LVEF to ≤ 35%. CONCLUSION: This study provides safety data of HER2-targeted therapies in patients with breast cancer and reduced LVEF while receiving cardioprotective medications and close cardiac monitoring. Our results demonstrate the importance of collaboration between cardiology and oncology providers to allow for delivery of optimal oncologic care to this unique population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10549-019-05191-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-65345132019-06-07 Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study Lynce, F. Barac, A. Geng, X. Dang, C. Yu, A. F. Smith, K. L. Gallagher, C. Pohlmann, P. R. Nunes, R. Herbolsheimer, P. Warren, R. Srichai, M. B. Hofmeyer, M. Cunningham, A. Timothee, P. Asch, F. M. Shajahan-Haq, A. Tan, M. T. Isaacs, C. Swain, S. M. Breast Cancer Res Treat Clinical Trial PURPOSE: HER2-targeted therapies have substantially improved the outcome of patients with breast cancer, however, they can be associated with cardiac toxicity. Guidelines recommend holding HER2-targeted therapies until resolution of cardiac dysfunction. SAFE-HEaRt is the first trial that prospectively tests whether these therapies can be safely administered without interruptions in patients with cardiac dysfunction. METHODS: Patients with stage I–IV HER2-positive breast cancer candidates for trastuzumab, pertuzumab or ado-trastuzumab emtansine (TDM-1), with left ventricular ejection fraction (LVEF) 40–49% and no symptoms of heart failure (HF) were enrolled. All patients underwent cardiology visits, serial echocardiograms and received beta blockers and ACE inhibitors unless contraindicated. The primary endpoint was completion of the planned HER2-targeted therapies without developing either a cardiac event (CE) defined as HF, myocardial infarction, arrhythmia or cardiac death or significant asymptomatic worsening of LVEF. The study was considered successful if planned oncology therapy completion rate was at least 30%. RESULTS: Of 31 enrolled patients, 30 were evaluable. Fifteen patients were treated with trastuzumab, 14 with trastuzumab and pertuzumab, and 2 with TDM-1. Mean LVEF was 45% at baseline and 46% at the end of treatment. Twenty-seven patients (90%) completed the planned HER2-targeted therapies. Two patients experienced a CE and 1 had an asymptomatic worsening of LVEF to ≤ 35%. CONCLUSION: This study provides safety data of HER2-targeted therapies in patients with breast cancer and reduced LVEF while receiving cardioprotective medications and close cardiac monitoring. Our results demonstrate the importance of collaboration between cardiology and oncology providers to allow for delivery of optimal oncologic care to this unique population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10549-019-05191-2) contains supplementary material, which is available to authorized users. Springer US 2019-03-09 2019 /pmc/articles/PMC6534513/ /pubmed/30852761 http://dx.doi.org/10.1007/s10549-019-05191-2 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Clinical Trial
Lynce, F.
Barac, A.
Geng, X.
Dang, C.
Yu, A. F.
Smith, K. L.
Gallagher, C.
Pohlmann, P. R.
Nunes, R.
Herbolsheimer, P.
Warren, R.
Srichai, M. B.
Hofmeyer, M.
Cunningham, A.
Timothee, P.
Asch, F. M.
Shajahan-Haq, A.
Tan, M. T.
Isaacs, C.
Swain, S. M.
Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study
title Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study
title_full Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study
title_fullStr Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study
title_full_unstemmed Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study
title_short Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study
title_sort prospective evaluation of the cardiac safety of her2-targeted therapies in patients with her2-positive breast cancer and compromised heart function: the safe-heart study
topic Clinical Trial
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534513/
https://www.ncbi.nlm.nih.gov/pubmed/30852761
http://dx.doi.org/10.1007/s10549-019-05191-2
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