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Trastuzumab-associated cardiac events in the Persephone trial
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Earl, Helena M, Vallier, Anne-Laure, Dunn, Janet A., Loi, Shrushma, Ogburn, Emma, McAdam, Karen, Hughes-Davies, Luke, Harnett, Adrian, Abraham, Jean, Wardley, Andrew, Cameron, David A, Miles, David, Gounaris, Ioannis, Plummer, Chris and Hiller, Louise (2016) Trastuzumab-associated cardiac events in the Persephone trial. British Journal of Cancer, 115 (12). pp. 1462-1470. doi:10.1038/bjc.2016.357 ISSN 0007-0920.
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Official URL: http://dx.doi.org/10.1038/bjc.2016.357
Abstract
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 greater than or equal to65%: 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.
Item Type: | Journal Article | ||||||||
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Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Clinical Trials Unit Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Breast -- Cancer -- Treatment, Trastuzumab, Clinical trials | ||||||||
Journal or Publication Title: | British Journal of Cancer | ||||||||
Publisher: | Nature Publishing Group | ||||||||
ISSN: | 0007-0920 | ||||||||
Official Date: | 6 December 2016 | ||||||||
Dates: |
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Volume: | 115 | ||||||||
Number: | 12 | ||||||||
Page Range: | pp. 1462-1470 | ||||||||
DOI: | 10.1038/bjc.2016.357 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||
Date of first compliant deposit: | 30 January 2017 | ||||||||
Date of first compliant Open Access: | 6 June 2017 | ||||||||
Funder: | National Institute for Health Research Health Technology Assessment (Great Britain) (NIHR HTA), Roche | ||||||||
Grant number: | Grant number 06/303/98 |
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