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Clinical Trial
. 2016 Dec 6;115(12):1462-1470.
doi: 10.1038/bjc.2016.357. Epub 2016 Nov 22.

Trastuzumab-associated cardiac events in the Persephone trial

Helena M Earl  1   2   3 , Anne-Laure Vallier  4 , Janet Dunn  5 , Shrushma Loi  5 , Emma Ogburn  5 , Karen McAdam  3   6 , Luke Hughes-Davies  1   3 , Adrian Harnett  7   8 , Jean Abraham  1   2   3 , Andrew Wardley  9 , David A Cameron  10 , David Miles  11 , Ioannis Gounaris  12   13 , Chris Plummer  14 , Louise Hiller  5
Affiliations
Clinical Trial

Trastuzumab-associated cardiac events in the Persephone trial

Helena M Earl et al. Br J Cancer. .

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 ⩾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.

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Conflict of interest statement

HME reports grants from NIHR HTA during the conduct of the study. JD reports grants from NIHR HTA during the conduct of the study. SL reports grants from NIHR HTA during the conduct of the study. LH reports grants from NIHR HTA during the conduct of the study. AW reports personal fees from Roche, outside the submitted work. DC reports his institution was paid for consultancy work by DC from Roche, outside the submitted work. A-LV, EO, AH, IG, CP, DM, LH-D, KM and JH declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flow chart of cardiac follow-up and events.
Figure 2
Figure 2
Random Effects modelling predicted lines and 95% CIs, split by randomised treatment arm.
See this image and copyright information in PMC

Comment in

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