Trastuzumab-associated cardiac events in the Persephone trial
<h4>Background</h4> <p>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.</p> <h4>Methods</h4> <p>Clinical cardiac events were defined as any...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
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Nature Publishing Group
2016
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| _version_ | 1797099210284204032 |
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| author | Earl, H Vallier, A Dunn, J Loi, S Ogburn, E McAdam, K Hughes-Davies, L Harnett, A Abraham, J Wardley, A Cameron, D Miles, D Gounaris, I Plummer, C Hiller, L |
| author_facet | Earl, H Vallier, A Dunn, J Loi, S Ogburn, E McAdam, K Hughes-Davies, L Harnett, A Abraham, J Wardley, A Cameron, D Miles, D Gounaris, I Plummer, C Hiller, L |
| author_sort | Earl, H |
| collection | OXFORD |
| description | <h4>Background</h4> <p>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.</p> <h4>Methods</h4> <p>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.</p> <h4>Results</h4> <p>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 (P¼0.01), and stopped treatment early in 8% (96/1214) of 12-month and 4% (45/1216) of 6-month patients (Po0.0001). Between 7 and 12 months, more 12-month than 6- month patients had LVEFso50% (8% vs 5%; P¼0.004). LVEFs showed quadratic change over time, and 6-month patients had a more rapid recovery (P¼0.02). 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 (P¼0.0002)). Lower baseline LVEF predicted more cardiac dysfunction in both arms (reference X65%: 55 to o65% OR 1.61 (95% CI 1.26–2.04); o55% OR 5.22 (3.42–7.95)) as did increasing age (reference o50: 50–59 OR 1.58 (1.17–2.12), 60–69 OR 1.91 (1.42–2.57)) 70þ 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)).</p> <h4>Conclusions</h4> <p>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.</p> |
| first_indexed | 2024-03-07T05:20:29Z |
| format | Journal article |
| id | oxford-uuid:deb6956f-7fe2-4805-bb0d-f6a07da83e39 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T05:20:29Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:deb6956f-7fe2-4805-bb0d-f6a07da83e392022-03-27T09:34:14ZTrastuzumab-associated cardiac events in the Persephone trialJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:deb6956f-7fe2-4805-bb0d-f6a07da83e39Symplectic Elements at OxfordNature Publishing Group2016Earl, HVallier, ADunn, JLoi, SOgburn, EMcAdam, KHughes-Davies, LHarnett, AAbraham, JWardley, ACameron, DMiles, DGounaris, IPlummer, CHiller, L <h4>Background</h4> <p>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.</p> <h4>Methods</h4> <p>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.</p> <h4>Results</h4> <p>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 (P¼0.01), and stopped treatment early in 8% (96/1214) of 12-month and 4% (45/1216) of 6-month patients (Po0.0001). Between 7 and 12 months, more 12-month than 6- month patients had LVEFso50% (8% vs 5%; P¼0.004). LVEFs showed quadratic change over time, and 6-month patients had a more rapid recovery (P¼0.02). 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 (P¼0.0002)). Lower baseline LVEF predicted more cardiac dysfunction in both arms (reference X65%: 55 to o65% OR 1.61 (95% CI 1.26–2.04); o55% OR 5.22 (3.42–7.95)) as did increasing age (reference o50: 50–59 OR 1.58 (1.17–2.12), 60–69 OR 1.91 (1.42–2.57)) 70þ 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)).</p> <h4>Conclusions</h4> <p>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.</p> |
| spellingShingle | Earl, H Vallier, A Dunn, J Loi, S Ogburn, E McAdam, K Hughes-Davies, L Harnett, A Abraham, J Wardley, A Cameron, D Miles, D Gounaris, I Plummer, C Hiller, L 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 |
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