Summary
Purpose
MA.17 was a double-blind placebo-controlled trial involving 5187 postmenopausal women that established letrozole to be of value in reducing recurrence of breast cancer when given in the extended adjuvant therapy setting after about 5 years of tamoxifen. Analyses were conducted to examine the relationships between duration of treatment on MA.17 and outcomes.
Methods
The final MA.17 database that included all events up to the date of unblinding of the study was interrogated. A non-parametric kernel smoothing method was used to estimate the hazard rates for disease-free survival (DFS), distant DFS (DDFS) and overall survival (OS) at 6, 12, 24, 36 and 48 months of follow-up and the hazard ratios (HRs) of letrozole to placebo were determined. The trend in HRs over time was tested based on a Cox model with a time-dependent covariate.
Results
Considering all patients, HRs for events in DFS and DDFS progressively decreased over time, favoring letrozole, with the trend being significant (p<0.0001 and p=0.0013, respectively) whereas the trend for OS was not significant. Considering the 2360 patients with node-positive status, the HRs for DFS, DDFS and OS all decreased over time with tests for trend all showing significance (p=0.0004, 0.0005 and 0.038, respectively). Considering the 2568 patients with node-negative status, the HRs for DFS decreased over time with the test for trend being significant (p=0.027) whereas the HRs for DDFS and OS showed no significant change over time.
Conclusion
These analyses suggest that, at least out to about 48 months, longer duration of letrozole treatment is associated with greater benefit in the extended adjuvant therapy setting.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu DS, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL, Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17 J Natl Cancer Inst 97:1262–1271, 2005
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy, hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials Lancet 365:1687–1717, 2005
Fisher B, Dignam J, Bryant J, Wolmark N, Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial J Natl Cancer Inst 93:684–690, 2001
National Cancer Institute clinical announcement: adjuvant therapy of breast cancer – tamoxifen update. National Institutes of Health, Bethesda (MD), 1995
Klein JP, Moeschberger ML, 1997 Survival Analysis: Techniques for Censored and Truncated Data. New York, Springer
Cheng MY, Hall P, Tu D: Confidence bands for hazard rate under random censoring. Biometrika (in press)
Tu D: Nonparametric estimate and confidence intervals for the hazard ratio based on censored data. Clin Trials 2: S36, 2005
Jones AL, Powles TJ, Law M, Tidy A, Easton D, Coombes RC, Smith IE, McKinna JA, Nash A, Ford HT, Gazet JC, Adjuvant aminoglutethimde for postmenopausal patients with primary breast cancer: analysis at 8 years J Clin Oncol 10:1547–1552, 1992
Acknowledgements
We are indebted to the women who participated in this study; to the trial committee; to the investigators, clinical research associates, and pharmacists from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), the Southwest Oncology Group, the Eastern Cooperative Oncology Group, the Cancer and Leukemia Group B, the North Central Cancer Treatment Group, the European Organization for Research and Treatment of Cancer, the International Breast Cancer Study Group, and centers in England including the Royal Marsden, St. George’s, and the Withington Hospitals; to the members of the Data Safety Monitoring Committee; and to the central office staff of the NCIC CTG who contributed to the conduct of the trial. The MA.17 study was supported by the Canadian Cancer Society through National Cancer Institute of Canada Grant 10362, grants from the National Cancer Institute of the United States (CA31946, CA21115, CA25224, CA38926 and CA32102), and Novartis Pharmaceuticals.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ingle, J.N., Tu, D., Pater, J.L. et al. Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial. Breast Cancer Res Treat 99, 295–300 (2006). https://doi.org/10.1007/s10549-006-9207-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-006-9207-y