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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
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(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. The Lancet, 393 (10191). pp. 2599-2612. doi:10.1016/S0140-6736(19)30650-6 ISSN 0140-6736.
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WRAP-6-versus-12-months-adjuvant-trastuzumab-HER2-positive-early-breast-cancer(PERSEPHONE)-Dunn-2019.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (579Kb) | Preview |
Official URL: http://dx.doi.org/10.1016/S0140-6736(19)30650-6
Abstract
Background
Adjuvant 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.
Methods
This 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).
Findings
Between 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).
Interpretation
We 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.
Item Type: | Journal Article | |||||||||||||||
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Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | |||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Clinical Trials Unit Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Trastuzumab, Breast -- Cancer -- Treatment | |||||||||||||||
Journal or Publication Title: | The Lancet | |||||||||||||||
Publisher: | Lancet Publishing Group | |||||||||||||||
ISSN: | 0140-6736 | |||||||||||||||
Official Date: | 6 June 2019 | |||||||||||||||
Dates: |
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Volume: | 393 | |||||||||||||||
Number: | 10191 | |||||||||||||||
Page Range: | pp. 2599-2612 | |||||||||||||||
DOI: | 10.1016/S0140-6736(19)30650-6 | |||||||||||||||
Status: | Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
Date of first compliant deposit: | 12 June 2019 | |||||||||||||||
Date of first compliant Open Access: | 13 June 2019 | |||||||||||||||
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