Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: Updated findings from NCIC CTG MA.17 Journal Article

Authors: Goss, P. E.; Ingle, J. N.; Martino, S.; Robert, N. J.; Muss, H. B.; Piccart, M. J.; Castiglione, M.; Tu, D.; 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.; Pater, J. L.
Article Title: Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: Updated findings from NCIC CTG MA.17
Abstract: Background: Most recurrences in women with breast cancer receiving 5 years of adjuvant tamoxifen occur after 5 years. The MA.17 trial, which was designed to determine whether extended adjuvant therapy with the aromatase inhibitor letrozole after tamoxifen reduces the risk of such late recurrences, was stopped early after an interim analysis showed that letrozole improved disease-free survival. This report presents updated findings from the trial. Methods: Postmenopausal women completing 5 years of tamoxifen treatment were randomly assigned to a planned 5 years of letrozole (n = 2593) or placebo (n = 2594). The primary endpoint was disease-free survival (DFS); secondary endpoints included distant disease-free survival, overall survival, incidence of contralateral tumors, and toxic effects. Survival was examined using Kaplan-Meier analysis and log-rank tests. Planned subgroup analyses included those by axillary lymph node status. All statistical tests were two-sided. Results: After a median follow-up of 30 months (range = 1.5-61.4 months), women in the letrozole arm had statistically significantly better DFS and distant DFS than women in the placebo arm (DFS: Hazard ratio [HR] for recurrence or contralateral breast cancer = 0.58, 95% confidence interval [CI] = 0.45 to 0.76; P<.001; distant DFS: HR = 0.60, 95% CI = 0.43 to 0.84; P = .002). Overall survival was the same in both arms (HR for death from any cause = 0.82, 95% CI = 0.57 to 1.19; P = .3). However, among lymph node-positive patients, overall survival was statistically significantly improved with letrozole (HR = 0.61, 95% CI = 0.38 to 0.98; P = .04). The incidence of contralateral breast cancer was lower in women receiving letrozole, but the difference was not statistically significant. Women receiving letrozole experienced more hormonally related side effects than those receiving placebo, but the incidences of bone fractures and cardiovascular events were the same. Conclusion: Letrozole after tamoxifen is well-tolerated and improves both disease-free and distant disease-free survival but not overall survival, except in node-positive patients. © The Author 2005. Published by Oxford University Press. All rights reserved.
Keywords: survival; cancer survival; controlled study; treatment outcome; aged; disease-free survival; middle aged; survival analysis; fracture; major clinical study; clinical trial; constipation; drug tolerability; fatigue; cancer recurrence; placebo; diarrhea; drug safety; hypertension; side effect; treatment planning; cancer adjuvant therapy; disease free survival; chemotherapy, adjuvant; follow up; lymph node metastasis; antineoplastic agent; cancer incidence; lymphatic metastasis; endometrium cancer; anorexia; edema; controlled clinical trial; infection; breast cancer; nausea; randomized controlled trial; antineoplastic combined chemotherapy protocols; myalgia; incidence; antineoplastic agents, phytogenic; aromatase inhibitor; vagina disease; bone pain; pathology; breast neoplasms; arthralgia; dizziness; dyspnea; confidence interval; axillary lymph node; insomnia; depression; chemistry; statistical analysis; statistical significance; cardiovascular disease; heart infarction; stroke; thromboembolism; adjuvant chemotherapy; arthritis; breast tumor; transient ischemic attack; tamoxifen; malignant neoplastic disease; receptors, estrogen; receptors, progesterone; headache; hot flush; letrozole; osteoporosis; kaplan meier method; hypercholesterolemia; estrogen receptor; progesterone receptor; double blind procedure; postmenopause; aromatase inhibitors; alopecia; femur fracture; disease exacerbation; triazoles; nitriles; nitrile; triazole derivative; hip fracture; vagina bleeding; sweating; angina pectoris; hazard assessment; ankle fracture; pelvis fracture; spine fracture; tibia fracture; wrist fracture
Journal Title: JNCI: Journal of the National Cancer Institute
Volume: 97
Issue: 17
ISSN: 0027-8874
Publisher: Oxford University Press  
Date Published: 2005-09-01
Start Page: 1262
End Page: 1271
Language: English
DOI: 10.1093/jnci/dji250
PUBMED: 16145047
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 588" - "Export Date: 24 October 2012" - "CODEN: JNCIA" - "Source: Scopus"
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MSK Authors
  1. Larry Norton
    692 Norton