6 versus 12 months of adjuvant trastuzumab in patients with HER2 positive breast cancer (PERSEPHONE): definitive 4-year disease-free survival results of an open label randomised phase 3 non-inferiority trial.
dc.contributor.author | Earl, HM | |
dc.contributor.author | Hiller, L | |
dc.contributor.author | Vallier, A | |
dc.contributor.author | Loi, S | |
dc.contributor.author | McAdam, K | |
dc.contributor.author | Hughes-Davis, L | |
dc.contributor.author | Harnett, AN | |
dc.contributor.author | Ah-See, M | |
dc.contributor.author | Simcock, R | |
dc.contributor.author | Rea, D | |
dc.contributor.author | Raj, S | |
dc.contributor.author | Woodings, P | |
dc.contributor.author | Harries, M | |
dc.contributor.author | Raynes, K | |
dc.contributor.author | Higgins, HB | |
dc.contributor.author | Wilcox, M | |
dc.contributor.author | Plummer, C | |
dc.contributor.author | Mansi, J | |
dc.contributor.author | Gounaris, I | |
dc.contributor.author | Mahler-Araujo, B | |
dc.contributor.author | Provenzano, E | |
dc.contributor.author | Chhabra, A | |
dc.contributor.author | Abraham, J | |
dc.contributor.author | Caldas, C | |
dc.contributor.author | Hall, PS | |
dc.contributor.author | McCabe, C | |
dc.contributor.author | Hulme, CT | |
dc.contributor.author | Miles, D | |
dc.contributor.author | Wardley, AM | |
dc.contributor.author | Cameron, DA | |
dc.contributor.author | Dunn, JA | |
dc.date.accessioned | 2019-06-25T14:37:34Z | |
dc.date.issued | 2019-06-06 | |
dc.description.abstract | Summary Background: Adjuvant trastuzumab significantly improves outcomes in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC). The standard duration is 12 months but shorter treatment could provide similar efficacy whilst reducing toxicities and cost. Methods: We randomly assigned patients with HER2 positive EBC to receive either 6-months or 12-months trastuzumab, in a phase 3 non-inferiority trial. Assuming a 4-year disease-free-survival (DFS) rate of 80% for the 12-month arm, 4000 patients were required to assess the non-inferiority of 6-months (5% 1-sided significance, 85% power), defining non-inferiority as no worse than 3% below the standard arm. A pre-planned, event-driven DFS analysis required 500 events. This trial is registered with EudraCT (2006-007018-39), ISRCTN (52968807), and ClinicalTrials.gov (NCT00712140). Findings: Between 4th October 2007 and 31st July 2015, 2045 patients were randomised to 12-months trastuzumab and 2043 to 6-months. 69% had ER-positive disease; all patients received chemotherapy (85% as adjuvant treatment); 90% received anthracyclines (48% with taxanes) and 10% taxane-only combinations; 53% had trastuzumab sequentially after chemotherapy. At 5·4 years median follow-up with 335 (8%) deaths, and 512 (13%) DFS events, 4-year DFS rates were 89·4% (95%CI, 87·9-90·7) in the 6-month group and 89·8% (95%CI 88·3-91·1) in the 12-month group (Hazard Ratio 1·07; 90%CI 0·93–1·24, non-inferiority p=0·01), demonstrating non-inferiority of 6-months trastuzumab. Congruent results were found for overall survival (OS) (non-inferiority p=0·001), and landmark analyses 6 months from starting trastuzumab (non-inferiority p=0·02 (DFS) and p=0·02 (OS)). 6-months trastuzumab resulted in fewer patients reporting severe adverse events (373/1939 (19%) versus 459/1894 (24%) 12-month patients, p=0·0002) or stopping early because of cardiotoxicity (61/1939 (3%) versus 146/1894 (8%) 12-month patients, p<0·0001). Interpretation: We have demonstrated 6-months trastuzumab is non-inferior to 12-months in HER2-positive EBC, with less cardiotoxicity and fewer severe adverse events. Funding: National Institute for Health Research, Health Technology Assessment Programme (grant number 06/303/98). | en_GB |
dc.description.sponsorship | National Institute for Health Research (NIHR) | en_GB |
dc.identifier.citation | Published online 06 June 2019 | en_GB |
dc.identifier.doi | 10.1016/S0140-6736(19)30650-6 | |
dc.identifier.grantnumber | 06/303/98 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/37671 | |
dc.language.iso | en | en_GB |
dc.publisher | Elsevier | en_GB |
dc.rights | © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. | en_GB |
dc.subject | PERSEPHONE | en_GB |
dc.subject | trastuzumab duration | en_GB |
dc.subject | early breast cancer | en_GB |
dc.subject | HER2 positive | en_GB |
dc.subject | adjuvant therapy | en_GB |
dc.title | 6 versus 12 months of adjuvant trastuzumab in patients with HER2 positive breast cancer (PERSEPHONE): definitive 4-year disease-free survival results of an open label randomised phase 3 non-inferiority trial. | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-06-25T14:37:34Z | |
dc.identifier.issn | 0140-6736 | |
dc.description | This is the author accepted manuscript. | en_GB |
dc.description | The final version is available from Elsevier via the DOI in this record. | en_GB |
dc.description | Data collected within the PERSEPHONE study will be made available to researchers whose full proposal for their use of the data has been approved by the PERSEPHONE Trial Management Group and whose research group includes a qualified statistician. The data required for the approved, specified purposes and the trial protocol will be provided, after completion of a data sharing agreement. Data sharing agreements will be set up by the sponsors of the trial, the funders, the trial coordination centre, and the Trial Steering and Management Groups. The data will be made available 2 years after publication. Please address requests for data to persephone@live.warwick.ac.uk. | en_GB |
dc.identifier.journal | Lancet | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2019-03-01 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2019-03-01 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-06-25T14:35:45Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2019-06-25T14:37:38Z | |
refterms.panel | A | en_GB |
refterms.depositException | publishedGoldOA |
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Except where otherwise noted, this item's licence is described as © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.