Six versus 12 months’ adjuvant trastuzumab in patients with HER2-positive early breast cancer: the PERSEPHONE non-inferiority RCT
| Autor: | Helena Earl, Louise Hiller, Anne-Laure Vallier, Shrushma Loi, Karen McAdam, Luke Hughes-Davies, Daniel Rea, Donna Howe, Kerry Raynes, Helen B Higgins, Maggie Wilcox, Chris Plummer, Betania Mahler-Araujo, Elena Provenzano, Anita Chhabra, Sophie Gasson, Claire Balmer, Jean E Abraham, Carlos Caldas, Peter Hall, Bethany Shinkins, Christopher McCabe, Claire Hulme, David Miles, Andrew M Wardley, David A Cameron, Janet A Dunn |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Health Technology Assessment, Vol 24, Iss 40 (2020) |
| Druh dokumentu: | article |
| ISSN: | 1366-5278 2046-4924 |
| DOI: | 10.3310/hta24400 |
| Popis: | Background: The addition of adjuvant trastuzumab to chemotherapy has significantly improved outcomes for people with human epidermal growth factor receptor 2 (HER2)-positive, early, potentially curable breast cancer. Twelve months’ trastuzumab, tested in registration trials, was adopted as standard adjuvant treatment in 2006. Subsequently, similar outcomes were demonstrated using 9 weeks of trastuzumab. Shorter durations were therefore tested for non-inferiority. Objectives: To establish whether or not 6 months’ adjuvant trastuzumab is non-inferior to 12 months’ in the treatment of HER2-positive early breast cancer using a primary end point of 4-year disease-free survival. Design: This was a Phase III randomised controlled non-inferiority trial. Setting: The setting was 152 NHS hospitals. Participants: A total of 4088 patients with HER2-positive early breast cancer who it was planned would receive both chemotherapy and trastuzumab took part. Intervention: Randomisation (1 : 1) to 6 months’ or 12 months’ trastuzumab treatment. Main outcomes: The primary end point was disease-free survival. The secondary end points were overall survival, cost-effectiveness and cardiac function during treatment with trastuzumab. Assuming a 4-year disease-free survival rate of 80% with 12 months’ trastuzumab, 4000 patients were required to demonstrate non-inferiority of 6 months’ trastuzumab (5% one-sided significance, 85% power), defining the non-inferiority limit as no worse than 3% below the standard arm. Costs and quality-adjusted life-years were estimated using a within-trial analysis and a lifetime decision-analytic model. Results: Between 4 October 2007 and 31 July 2015, 2045 patients were randomised to 12 months’ trastuzumab and 2043 were randomised to 6 months’ trastuzumab. Sixty-nine per cent of patients had ER-positive disease; 90% received anthracyclines (49% with taxanes; 41% without taxanes); 10% received taxanes without anthracyclines; 54% received trastuzumab sequentially after chemotherapy; and 85% received adjuvant chemotherapy (58% were node negative). At 6.1 years’ median follow-up, with 389 (10%) deaths and 566 (14%) disease-free survival events, the 4-year disease-free survival rates for the 4088 patients were 89.5% (95% confidence interval 88.1% to 90.8%) in the 6-month group and 90.3% (95% confidence interval 88.9% to 91.5%) in the 12-month group (hazard ratio 1.10, 90% confidence interval 0.96 to 1.26; non-inferiority p = 0.01), demonstrating non-inferiority of 6 months’ trastuzumab. Congruent results were found for overall survival (non-inferiority p = 0.0003) and landmark analyses 6 months from starting trastuzumab [non-inferiority p = 0.03 (disease-free-survival) and p = 0.006 (overall survival)]. Six months’ trastuzumab resulted in fewer patients reporting adverse events of severe grade [365/1929 (19%) vs. 460/1935 (24%) for 12-month patients; p = 0.0003] or stopping early because of cardiotoxicity [61/1977 (3%) vs. 146/1941 (8%) for 12-month patients; p |
| Databáze: | Directory of Open Access Journals |
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