Evidence map›Paper›PMID 31178152›Full record

Trial reportLancet (London, England)2019

6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial.

Helena M Earl, Louise Hiller, Anne-Laure Vallier, Shrushma Loi, Karen McAdam, Luke Hughes-Davies, Adrian N Harnett, Mei-Lin Ah-See, Richard Simcock, Daniel Rea and 23 more

Registry-linked trialAbstract readClinical Trial, Phase IIIComparative StudyEquivalence Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Lancet (London, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00712140 (Persephone), which is not on this map. Cited by 146 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed, 9 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.

NCT00712140 phase3unknown statusnot on this map

Persephone: Duration of Trastuzumab With Chemotherapy in Women With Early Stage Breast Cancer: Six Months Versus Twelve

TypeinterventionalSponsorWarwick Medical SchoolRan2007Enrolled4,000ConditionsBreast CancerArmstrastuzumab, parenteral chemotherapy
3 · Its place in the literature

Who cites it

146 citing papers in PubMed, 9 syntheses or guidelines pooled it.

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86 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors.

Helena M EarlDepartment of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Cambridge Breast Cancer Research Unit, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK; National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK. Electronic address: hme22@cam.ac.uk.
Louise HillerWarwick Clinical Trials Unit, University of Warwick, Coventry, UK.
Anne-Laure VallierCambridge Clinical Trials Unit-Cancer Theme, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK.
Shrushma LoiWarwick Clinical Trials Unit, University of Warwick, Coventry, UK.
Karen McAdamDepartment of Oncology, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK; Department of Oncology, North West Anglia NHS Foundation Trust, Peterborough City Hospital, Peterborough, UK.
Luke Hughes-DaviesDepartment of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Department of Oncology, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK.
Adrian N HarnettDepartment of Oncology, James Paget University Hospital, Norfolk, UK; Department of Oncology, Norfolk & Norwich University Hospital, Norwich, UK.
Mei-Lin Ah-SeeMedical Oncology, Mount Vernon Cancer Centre, Northwood, UK.
Richard SimcockSussex Cancer Centre, Brighton and Sussex University Hospitals NHS, Brighton, UK.
Daniel ReaCancer Research UK Clinical Trials Unit and Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Sanjay RajDepartment of Oncology, Southampton University Hospital NHS Foundation Trust, Southampton, UK.
Pamela WoodingsDepartment of Oncology, Royal Derby Hospital, Derby, UK.
Mark HarriesDepartment of Medical Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Donna HoweWarwick Clinical Trials Unit, University of Warwick, Coventry, UK.
Kerry RaynesWarwick Clinical Trials Unit, University of Warwick, Coventry, UK.
Helen B HigginsWarwick Clinical Trials Unit, University of Warwick, Coventry, UK.
Maggie WilcoxIndependent Cancer Patients Voice, London, UK.
Chris PlummerDepartment of Cardiology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Freeman Hospital, Newcastle upon Tyne, UK.
Janine MansiDepartment of Medical Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Ioannis GounarisOncology Global Drug Development, Novartis, Basel, Switzerland.
Betania Mahler-AraujoMetabolic Research Laboratories, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Department of Histopathology, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK.
Elena ProvenzanoDepartment of Histopathology, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK; National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK.
Anita ChhabraPharmacy, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK.
Jean E AbrahamDepartment of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Cambridge Breast Cancer Research Unit, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK; National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK.
Carlos CaldasDepartment of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Cambridge Breast Cancer Research Unit, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK; National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK; Cancer Research UK Cambridge Institute, University of Cambridge Li Ka Shing Centre, Cambridge, UK.
Peter S HallCancer Edinburgh Research Centre, The Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Christopher McCabeInstitute of Health Economics, Edmonton, Canada.
Claire HulmeAcademic Unit of Health Economics, University of Leeds, Leeds, UK; Health Economics Group, Institute of Health Research, University of Exeter Medical School, Exeter, UK.
David MilesMedical Oncology, Mount Vernon Cancer Centre, Northwood, UK.
Andrew M WardleyResearch & Development, The NIHR Manchester Clinical Research Facility at The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, Faculty of Biology, Medicine and Health, ManchesterAcademic Health Science Centre, University of Manchester, Manchester, UK.
David A CameronCancer Edinburgh Research Centre, The Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Janet A DunnWarwick Clinical Trials Unit, University of Warwick, Coventry, UK.
PERSEPHONE Steering Committee and Trial Investigators

Funding

Cancer Research UK 18832Cancer Research UK 9675Department of Health
6 · The paper itself

Abstract

backgroundAdjuvant trastuzumab significantly improves outcomes for patients with HER2-positive early breast cancer. The standard treatment duration is 12 months but shorter treatment could provide similar efficacy while reducing toxicities and cost. We aimed to investigate whether 6-month adjuvant trastuzumab treatment is non-inferior to the standard 12-month treatment regarding disease-free survival.

methodsThis study is an open-label, randomised phase 3 non-inferiority trial. Patients were recruited from 152 centres in the UK. We randomly assigned patients with HER2-positive early breast cancer, aged 18 years or older, and with a clear indication for chemotherapy, by a computerised minimisation process (1:1), to receive either 6-month or 12-month trastuzumab delivered every 3 weeks intravenously (loading dose of 8 mg/kg followed by maintenance doses of 6 mg/kg) or subcutaneously (600 mg), given in combination with chemotherapy (concurrently or sequentially). The primary endpoint was disease-free survival, analysed by intention to treat, with a non-inferiority margin of 3% for 4-year disease-free survival. Safety was analysed in all patients who received trastuzumab. This trial is registered with EudraCT (number 2006-007018-39), ISRCTN (number 52968807), and ClinicalTrials.gov (number NCT00712140).

findingsBetween Oct 4, 2007, and July 31, 2015, 2045 patients were assigned to 12-month trastuzumab treatment and 2044 to 6-month treatment (one patient was excluded because they were double randomised). Median follow-up was 5·4 years (IQR 3·6-6·7) for both treatment groups, during which a disease-free survival event occurred in 265 (13%) of 2043 patients in the 6-month group and 247 (12%) of 2045 patients in the 12-month group. 4-year disease-free survival was 89·4% (95% CI 87·9-90·7) in the 6-month group and 89·8% (88·3-91·1) in the 12-month group (hazard ratio 1·07 [90% CI 0·93-1·24], non-inferiority p=0·011), showing non-inferiority of the 6-month treatment. 6-month trastuzumab treatment resulted in fewer patients reporting severe adverse events (373 [19%] of 1939 patients vs 459 [24%] of 1894 patients, p=0·0002) or stopping early because of cardiotoxicity (61 [3%] of 1939 patients vs 146 [8%] of 1894 patients, p<0·0001).

interpretationWe have shown that 6-month trastuzumab treatment is non-inferior to 12-month treatment in patients with HER2-positive early breast cancer, with less cardiotoxicity and fewer severe adverse events. These results support consideration of reduced duration trastuzumab for women at similar risk of recurrence as to those included in the trial.

fundingUK National Institute for Health Research, Health Technology Assessment Programme.

Indexed as

AdultAgedAged, 80 and overAntineoplastic Agents, ImmunologicalBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalDrug Administration ScheduleErb-b2 Receptor Tyrosine KinasesFemaleHumansInfusions, IntravenousInjections, SubcutaneousMiddle AgedProspective StudiesTrastuzumabAntineoplastic Agents, ImmunologicalERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesTrastuzumab

Identifiers

PMID31178152
PMCPMC6615016

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Registered trials

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.