Updated analysis of the NCIC CTG MA.17 randomized placebo (P) controlled trial of letrozole (L) after five years of tamoxifen in postmenopausal women with early stage breast cancer

Abstract

847 Background: Over half of recurrences and two thirds of deaths from hormone dependent breast cancer occur after completion of 5 years of adjuvant tamoxifen. We previously reported an improvement in disease free survival in women receiving extended adjuvant treatment with L after tamoxifen. Toxicities reported up until February 2003, 8 months prior to unblinding of the study medication, were low grade and included vasomotor symptoms, arthritis, joint and muscle pain. Hypercholesterolemia and cardiovascular events were similar in both arms and while new patient-reported diagnoses of osteoporosis were slightly more common (5.8% vs 4.5% L vs P), clinical fracture rate was unchanged by L. Methods: The study database was locked as of August 2003 for analysis of events in disease free survival (DFS) which were local or distant recurrence or new contralateral breast cancer. A subset analysis of outcome according to nodal status was performed. A full and updated analysis of all study endpoints, including safety and quality of life, as of the date of unblinding the trial (October 9 2003) will be conducted in mid-January 2004. Results: 5187 patients were randomized. Demonstration of an improvement in DFS was achieved earlier than anticipated (P = 0.00008 at the first interim analysis) with a hazard rate of 0.57, indicating a 43% reduction in risk. L decreased the risk of events by 53% and 40% for node negative and node positive patients respectively. This translated into an absolute improvement in 3-year disease free survival of 3% and 7% in node negative and node positive patients, respectively. Conclusions: Letrozole is indicated as extended adjuvant therapy for the majority of breast cancer patients completing about 5 years of tamoxifen regardless of nodal status. Further data from the updated analysis will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis; Pfizer Novartis; Pfizer AstraZeneca; Novartis