Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA.17 Journal Article
| Authors: | Ingle, J. N.; Tu, D.; Pater, J. L.; Muss, H. B.; Martino, S.; Robert, N. J.; Piccart, M. J.; Castiglione, M.; Shepherd, L. E.; Pritchard, K. I.; Livingston, R. B.; Davidson, N. E.; Norton, L.; Perez, E. A.; Abrams, J. S.; Cameron, D. A.; Palmer, M. J.; Goss, P. E. |
| Article Title: | Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA.17 |
| Abstract: | Background: MA.17 evaluated letrozole or placebo after 5 years of tamoxifen and showed significant improvement in disease-free survival (DFS) for letrozole [hazard ratio (HR) 0.57, P = 0.00008]. The trial was unblinded and placebo patients were offered letrozole. Patients and methods: An intent-to-treat analysis of all outcomes, before and after unblinding, on the basis of the original randomization was carried out. Results: In all, 5187 patients were randomly allocated to the study at baseline and, at unblinding, 1579 (66%) of 2383 placebo patients accepted letrozole. At median follow-up of 64 months (range 16-95), 399 recurrences or contralateral breast cancers (CLBCs) (164 letrozole and 235 placebo) occurred. Four-year DFS was 94.3% (letrozole) and 91.4% (placebo) [HR 0.68, 95% confidence interval (CI) 0.55-0.83, P = 0.0001] and showed superiority for letrozole in both node-positive and -negative patients. Corresponding 4-year distant DFS was 96.3% and 94.9% (HR 0.80, 95% CI 0.62-1.03, P = 0.082). Four-year overall survival was 95.1% for both groups. The annual rate of CLBC was 0.28% for letrozole and 0.46% for placebo patients (HR 0.61, 95% CI 0.39-0.97, P = 0.033). Conclusions: Patients originally randomly assigned to receive letrozole within 3 months of stopping tamoxifen did better than placebo patients in DFS and CLBC, despite 66% of placebo patients taking letrozole after unblinding. © The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. |
| Keywords: | controlled study; disease-free survival; major clinical study; overall survival; clinical trial; cancer recurrence; placebo; antineoplastic agents; adjuvant therapy; cancer adjuvant therapy; disease free survival; chemotherapy, adjuvant; follow up; lymphatic metastasis; controlled clinical trial; breast cancer; randomized controlled trial; proportional hazards models; estrogens; recurrence; breast neoplasms; kaplan-meiers estimate; early cancer; tamoxifen; letrozole; neoplasms, second primary; antineoplastic agents, hormonal; double blind procedure; double-blind method; postmenopause; aromatase inhibitors; triazoles; nitriles; patient acceptance of health care; placebos; neoplasms, hormone-dependent; progesterone; extended adjuvant therapy; intent-to-treat |
| Journal Title: | Annals of Oncology |
| Volume: | 19 |
| Issue: | 5 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2008-01-01 |
| Start Page: | 877 |
| End Page: | 882 |
| Language: | English |
| DOI: | 10.1093/annonc/mdm566 |
| PUBMED: | 18332043 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 16" - "Export Date: 17 November 2011" - "CODEN: ANONE" - "Source: Scopus" |
