Evidence map›Paper›PMID 27875516›Full record

Trial reportBritish journal of cancer2016

Trastuzumab-associated cardiac events in the Persephone trial.

Helena M Earl, Anne-Laure Vallier, Janet Dunn, Shrushma Loi, Emma Ogburn, Karen McAdam, Luke Hughes-Davies, Adrian Harnett, Jean Abraham, Andrew Wardley and 5 more

Abstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in British journal of cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Caught in the crossfire: cardiac complications of cancer therapy.The Journal of clinical investigation · 2026
    Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Progress in adjuvant systemic therapy for breast cancer.Nature reviews. Clinical oncology · 2019
    Review
  10. Article
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Helena M EarlDepartment of Oncology, University of Cambridge, (Box 193-R4) Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
Anne-Laure VallierCambridge Clinical Trials Unit - Cancer Theme, Cambridge University NHS Foundation Trust, Box 279 (S4), Hills Road, Cambridge CB2 0QQ, UK.
Janet DunnWarwick Clinical Trials Unit, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
Shrushma LoiWarwick Clinical Trials Unit, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
Emma OgburnWarwick Clinical Trials Unit, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
Karen McAdamCambridge Breast Unit and Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK.
Luke Hughes-DaviesDepartment of Oncology, University of Cambridge, (Box 193-R4) Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
Adrian HarnettNorfolk & Norwich University Hospital, Colney Lane, Norwich NR4 7UY, UK.
Jean AbrahamDepartment of Oncology, University of Cambridge, (Box 193-R4) Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
Andrew WardleyThe Christie NHS Foundation Trust, 550 Wilmslow Rd, Manchester M20 4BX, UK.
David A CameronUniversity of Edinburgh Cancer Research Centre, IGMM, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UK.
David MilesMount Vernon Cancer Centre, Rickmansworth Rd, Northwood, London HA6 2RN, UK.
Ioannis GounarisCancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK.
Chris PlummerDepartment of Cardiology, Freeman Hospital, Freeman Rd, Newcastle upon Tyne, Tyne and Wear NE7 7DN, UK.
Louise HillerWarwick Clinical Trials Unit, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.

Funding

Department of Health 06/303/98
6 · The paper itself

Abstract

backgroundWe 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.

methodsClinical 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.

resultsA 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)).

conclusionsWe 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.

Indexed as

AdultAgedAged, 80 and overAntineoplastic AgentsHeart FailureHumansMiddle AgedTrastuzumabYoung AdultAntineoplastic AgentsTrastuzumab

Identifiers

PMID27875516
PMCPMC5155357

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.