Annals of Oncology Advance Access originally published online on March 10, 2008
Annals of Oncology 2008 19(5):877-882; doi:10.1093/annonc/mdm566
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breast cancer |
Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA.17
1 Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA
2 National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada
3 Division of Hematology/Oncology, University of Vermont, Burlington, VT
4 Angeles Clinic and Research Institute, Santa Monica, CA
5 Inova Fairfax Hospital, Falls Church, VA, USA
6 Chemotherapy Department, Institut Jules Bordet, Brussels, Belgium
7 International Breast Cancer Study Group Coordinating Center, Bern, Switzerland
8 Department of Medicine, Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario, Canada
9 Arizona Cancer Center, Tucson, AZ
10 Department of Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD
11 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY
12 Division of Hematology/Oncology, Mayo Clinic, Jacksonville, FL
13 Clinical Investigations Branch, National Cancer Institute, Rockville, MD, USA
14 National Cancer Research Network, University of Leeds, Leeds, UK
15 Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA
* Correspondence to: Dr J. N. Ingle, Division of Medical Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Tel: +1-507-284-2511; Fax: +1-507-284-1803; E-mail: ingle.james{at}mayo.edu
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.
Key words: extended adjuvant therapy, intent-to-treat, letrozole
Received for publication September 19, 2007. Revision received November 20, 2007. Accepted for publication November 22, 2007.
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