Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA.17

James N. Ingle, D. Tu, J. L. Pater, H. B. Muss, S. Martino, N. J. Robert, M. J. Piccart, M. Castiglione, L. E. Shepherd, K. I. Pritchard, R. B. Livingston, N. E. Davidson, L. Norton, E. A. Perez, J. S. Abrams, D. A. Cameron, M. J. Palmer, P. E. Goss

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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.

Original languageEnglish (US)
Pages (from-to)877-882
Number of pages6
JournalAnnals of Oncology
Volume19
Issue number5
DOIs
StatePublished - May 1 2008

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Keywords

  • Extended adjuvant therapy
  • Intent-to-treat
  • Letrozole

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

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. (2008). Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA.17. Annals of Oncology, 19(5), 877-882. https://doi.org/10.1093/annonc/mdm566