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Trastuzumab-associated cardiac events in the Persephone trial
BACKGROUND: We report cardiac events in the Persephone trial which compares 6–12 months of adjuvant trastuzumab in women with confirmed HER2-positive, early-stage breast cancer. METHODS: Clinical cardiac events were defined as any of the following: symptoms and/or signs of congestive heart failure (...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155357/ https://www.ncbi.nlm.nih.gov/pubmed/27875516 http://dx.doi.org/10.1038/bjc.2016.357 |
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author | Earl, Helena M Vallier, Anne-Laure Dunn, Janet Loi, Shrushma Ogburn, Emma McAdam, Karen Hughes-Davies, Luke Harnett, Adrian Abraham, Jean Wardley, Andrew Cameron, David A Miles, David Gounaris, Ioannis Plummer, Chris Hiller, Louise |
author_facet | Earl, Helena M Vallier, Anne-Laure Dunn, Janet Loi, Shrushma Ogburn, Emma McAdam, Karen Hughes-Davies, Luke Harnett, Adrian Abraham, Jean Wardley, Andrew Cameron, David A Miles, David Gounaris, Ioannis Plummer, Chris Hiller, Louise |
author_sort | Earl, Helena M |
collection | PubMed |
description | BACKGROUND: We report cardiac events in the Persephone trial which compares 6–12 months of adjuvant trastuzumab in women with confirmed HER2-positive, early-stage breast cancer. METHODS: Clinical cardiac events were defined as any of the following: symptoms and/or signs of congestive heart failure (CHF) and new or altered CHF medication. In addition, left ventricular ejection fraction (LVEF) was measured at baseline and then 3 monthly for 12 months. RESULTS: A total of 2500 patients, aged 22–82, were included: 1251 randomised to 12 months and 1249 to 6 months of trastuzumab treatment. A total of 93% (2335/2500) received anthracyclines, 49% of these (1136/2335) with taxanes. Cardiotoxicity delayed treatment in 6% of 12-month and 4% of 6-month patients (P=0.01), and stopped treatment early in 8% (96/1214) of 12-month and 4% (45/1216) of 6-month patients (P<0.0001). Between 7 and 12 months, more 12-month than 6-month patients had LVEFs<50% (8% vs 5% P=0.004). LVEFs showed quadratic change over time, and 6-month patients had a more rapid recovery (P=0.02). In a landmark analysis twice as many 12-month patients, free of cardiac events at 6 months, had cardiac problems in months 7–12 (6% (66/1046) vs 3% (29/1035) of 6-month patients (P=0.0002)). Lower baseline LVEF predicted more cardiac dysfunction in both arms (reference ⩾65%: 55 to <65% OR 1.61 (95% CI 1.26–2.04); <55% OR 5.22 (3.42–7.95)) as did increasing age (reference <50: 50–59 OR 1.58 (1.17–2.12), 60–69 OR 1.91 (1.42–2.57)) 70+ OR 2.72 (1.82–4.08)) and prior use of cardiac medication (OR 8.46 (4.69–15.25)). >3 cycles of anthracycline was associated with higher risk of cardiac events only for 12-month patients (OR 1.41 (1.04–1.90)), and not for 6-month patients (OR 1.28 (0.91–1.79)). CONCLUSIONS: We demonstrate significantly fewer cardiac events from 6 months of adjuvant trastuzumab compared with that from 12 months. This cardiac signal adds importance to the question of the optimum duration of adjuvant trastuzumab treatment. If 6 months is proven to have non-inferior outcomes to 12 months treatment, these data would support 6 months as the standard of care. |
format | Online Article Text |
id | pubmed-5155357 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51553572017-12-06 Trastuzumab-associated cardiac events in the Persephone trial Earl, Helena M Vallier, Anne-Laure Dunn, Janet Loi, Shrushma Ogburn, Emma McAdam, Karen Hughes-Davies, Luke Harnett, Adrian Abraham, Jean Wardley, Andrew Cameron, David A Miles, David Gounaris, Ioannis Plummer, Chris Hiller, Louise Br J Cancer Clinical Study BACKGROUND: We report cardiac events in the Persephone trial which compares 6–12 months of adjuvant trastuzumab in women with confirmed HER2-positive, early-stage breast cancer. METHODS: Clinical cardiac events were defined as any of the following: symptoms and/or signs of congestive heart failure (CHF) and new or altered CHF medication. In addition, left ventricular ejection fraction (LVEF) was measured at baseline and then 3 monthly for 12 months. RESULTS: A total of 2500 patients, aged 22–82, were included: 1251 randomised to 12 months and 1249 to 6 months of trastuzumab treatment. A total of 93% (2335/2500) received anthracyclines, 49% of these (1136/2335) with taxanes. Cardiotoxicity delayed treatment in 6% of 12-month and 4% of 6-month patients (P=0.01), and stopped treatment early in 8% (96/1214) of 12-month and 4% (45/1216) of 6-month patients (P<0.0001). Between 7 and 12 months, more 12-month than 6-month patients had LVEFs<50% (8% vs 5% P=0.004). LVEFs showed quadratic change over time, and 6-month patients had a more rapid recovery (P=0.02). In a landmark analysis twice as many 12-month patients, free of cardiac events at 6 months, had cardiac problems in months 7–12 (6% (66/1046) vs 3% (29/1035) of 6-month patients (P=0.0002)). Lower baseline LVEF predicted more cardiac dysfunction in both arms (reference ⩾65%: 55 to <65% OR 1.61 (95% CI 1.26–2.04); <55% OR 5.22 (3.42–7.95)) as did increasing age (reference <50: 50–59 OR 1.58 (1.17–2.12), 60–69 OR 1.91 (1.42–2.57)) 70+ OR 2.72 (1.82–4.08)) and prior use of cardiac medication (OR 8.46 (4.69–15.25)). >3 cycles of anthracycline was associated with higher risk of cardiac events only for 12-month patients (OR 1.41 (1.04–1.90)), and not for 6-month patients (OR 1.28 (0.91–1.79)). CONCLUSIONS: We demonstrate significantly fewer cardiac events from 6 months of adjuvant trastuzumab compared with that from 12 months. This cardiac signal adds importance to the question of the optimum duration of adjuvant trastuzumab treatment. If 6 months is proven to have non-inferior outcomes to 12 months treatment, these data would support 6 months as the standard of care. Nature Publishing Group 2016-12-06 2016-11-22 /pmc/articles/PMC5155357/ /pubmed/27875516 http://dx.doi.org/10.1038/bjc.2016.357 Text en Copyright © 2016 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Clinical Study Earl, Helena M Vallier, Anne-Laure Dunn, Janet Loi, Shrushma Ogburn, Emma McAdam, Karen Hughes-Davies, Luke Harnett, Adrian Abraham, Jean Wardley, Andrew Cameron, David A Miles, David Gounaris, Ioannis Plummer, Chris Hiller, Louise Trastuzumab-associated cardiac events in the Persephone trial |
title | Trastuzumab-associated cardiac events in the Persephone trial |
title_full | Trastuzumab-associated cardiac events in the Persephone trial |
title_fullStr | Trastuzumab-associated cardiac events in the Persephone trial |
title_full_unstemmed | Trastuzumab-associated cardiac events in the Persephone trial |
title_short | Trastuzumab-associated cardiac events in the Persephone trial |
title_sort | trastuzumab-associated cardiac events in the persephone trial |
topic | Clinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155357/ https://www.ncbi.nlm.nih.gov/pubmed/27875516 http://dx.doi.org/10.1038/bjc.2016.357 |
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