Letrozole versus anastrozole in postmenopausal women with chemotherapy-refractory negative HER-2 metastatic breast cancer: a randomised, multicentre, open-label, non-inferiority phase 3 study

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Research Article 
American Journal of BioMedicine Volume 2, Issue 4, pages 431–440
Received December 15, 2013; accepted March 01, 2014; published April 29, 2014

Alex J Danielsona, Nasser Ghaly Yousifa, Dan G. Wanga, b,  Alexey F Maltzmana, Howell G Johnstona, Aman S Gomeza, Han Leeamail of corresponding author


Breast cancer is the most common form of cancer affecting elderly women in worldwide, although the usually reported incidence of breast cancer is close to 50% in women 65 years or older, reaching 47% after 70 years in the updated Surveillance, Epidemiology, and End Results (SEER) database. Third-generation aromatase inhibitors are being considered as an alternative to tamoxifen as first-line therapy for advanced breast cancer. These newer therapies are more expensive, and will gain greater acceptance if they can demonstrate cost-effectiveness. We assessed the efficacy and toxicity of letrozole versus anastrozole in these patients. For this randomized, open-label, phase 3 head-to-head study, we enrolled patients (from centers in North America, Europe, Africa, Australia and Asia) aged 65 years or older with chemotherapy-refractory metastatic breast cancer, ECOG performance status of 2 or less. Using a computer-generated randomization sequence, we assigned patients to receive letrozole or anastrozole. The primary endpoint was overall survival assessed for non-inferiority (retention of ≥50% of the letrozole treatment effect; historical hazard ratio [HR] for letrozole vs best anastrozole 0·55). The data from this study show that letrozole is at least as effective as anastrozole as first-line therapy of metestatic breast cancer in postmenopausal women. A total of 56.7% of patients in the letrozole group and 41.3% of patients in the anastrozole group gained clinical benefit from treatment.

Keywords: Breast cancer; SEER; Letrozole; anastrozole; ECOG; Chemotherapy-refractory

Copyright © 2014 by The American Society for BioMedicine and BM-Publisher, Inc.

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