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.
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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.
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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
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DOI: https://doi.org/10.1007/s10549-006-9207-y