On April 30, 2010, the U.S. Food and Drug Administration converted
letrozole (Femara®; Novartis Pharmaceuticals Corporation, East Hanover, NJ) from accelerated to full approval for adjuvant and extended adjuvant (following 5 years of
tamoxifen) treatment of postmenopausal women with
hormone receptor-positive early
breast cancer. The initial accelerated approvals of
letrozole for adjuvant and extended adjuvant treatment on December 28, 2005 and October 29, 2004, respectively, were based on an analysis of the disease-free survival (DFS) outcome of patients followed for medians of 26 months and 28 months, respectively. Both trials were double-blind, multicenter studies. Both trials were unblinded early when an interim analysis showed a favorable
letrozole effect on DFS. In updated intention-to-treat analyses of both trials, the risk for a DFS event was lower with
letrozole than with
tamoxifen (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77-0.99; p = .03) in the adjuvant trial and was lower than with placebo (HR, 0.89; 95% CI, 0.76-1.03; p = .12) in the extended adjuvant trial. The latter analysis ignores the interim switch of 60% of placebo-treated patients to
letrozole.
Bone fractures and
osteoporosis were reported more frequently following treatment with
letrozole whereas
tamoxifen was associated with a higher risk for endometrial proliferation and
endometrial cancer.
Myocardial infarction was more frequently reported with
letrozole than with
tamoxifen, but the incidence of thromboembolic events was higher with
tamoxifen than with
letrozole.
Lipid-lowering medications were required for 25% of patients on
letrozole and 16% of patients on
tamoxifen.