Letrozole (
Femara), an
aromatase inhibitor that blocks
estrogen synthesis by inhibiting the final step of the
estrogen biosynthetic pathway, is approved for use in a wide range of
breast cancer settings. Randomised clinical trials in postmenopausal women with
hormone-responsive early-stage
breast cancer have demonstrated that, as adjuvant
therapy,
letrozole has greater efficacy than
tamoxifen. It is also more effective than placebo as extended adjuvant
therapy after completion of
tamoxifen therapy in these patients. In women with
hormone-responsive advanced
breast cancer,
letrozole is superior to
tamoxifen in prolonging the time to
disease progression and
time to treatment failure in a first-line setting, and is at least as effective as
anastrozole and more effective than
megestrol for some endpoints (in one of two trials) in a second-line setting.
Letrozole is generally well tolerated, and in a health-related quality-of-life analysis from a large clinical trial, patient well-being with
letrozole as extended adjuvant
therapy did not differ from that with placebo. Modelled analyses from the UK and the US suggest that, in postmenopausal women with
hormone-receptor-positive early-stage
breast cancer,
letrozole is likely to be a cost-effective alternative to
tamoxifen as adjuvant
therapy; moreover, using
letrozole as extended adjuvant
therapy after
tamoxifen, rather than no further treatment, is also a cost-effective treatment strategy. Sensitivity analyses have shown these results to be robust. In terms of direct healthcare costs, pharmacoeconomic models suggest that
letrozole is a cost-effective alternative to
tamoxifen as first-line
therapy in postmenopausal women with
hormone-responsive advanced
breast cancer from the perspectives of the UK NHS, the Canadian and Italian public healthcare systems and the Japanese national health insurance system. Incremental costs per QALY or progression-free year gained over
tamoxifen were well within the recommended limits for acceptability of new agents that are more effective and more expensive than existing
therapies in the UK, Japan and Canada. Modelled analyses from the UK and Canada have also suggested that
letrozole is cost effective as second-line
therapy for advanced
breast cancer in postmenopausal women who have
disease progression following anti-
estrogen therapy. In conclusion,
letrozole is an effective and well tolerated treatment for postmenopausal women with early-stage or advanced
hormone-responsive
breast cancer. Pharmacoeconomic analyses from UK and North American perspectives support the use of
letrozole in
hormone-responsive early-stage
breast cancer in both the adjuvant and extended adjuvant settings. In addition, other modelled analyses conducted in a variety of healthcare systems across different countries consistently suggest that
letrozole is cost effective in advanced treatment settings.