Aromatase inhibitors (anastrozole, letrozole and examestane) for adjuvant therapy in early breast cancer

AUGUSTOVSKI, F; PICHON-RIVIERE A,; ALCARAZ A; BARDACH, ARIEL; GARCIA MARTÍ, SEBASTIAN; LOPEZ, A; GLUJOVSKY, D; REGUEIRO, A

Documentos de Evaluación de Tecnologías Sanitarias

IECS

Año: 2006 p. 1 - 30

1668-2793

This report is intended to assess the usefulness of aromatase inhibitors (AIs) as adjuvant systematic therapy in postmenopausal women with early hormone-sensitive breast cancer.12 reviews, 7 randomized clinical trials, 3 pharmacoeconomic studies and position statements papers issued by international oncology associations were selected for this report.The Arimidex, Tamoxifen, Alone or in Combination (ATAC) study which recruited more than 9,000 postmenopausal women reports that anastrozole showed a relative risk of 0.83 (CI 95% 0.73-0.94) as compared with tamoxifen for disease-free survival. This study has a follow-up of 68 months. The difference in absolute risk was 2.4% for the abovementioned result in favor of anastrozole. According to the Breast International Group (BIG) 01-98 study, at a 26 month follow-up median letrozole showed significantly longer disease-free survival (RR 0.81; 95% CI 0.70-0.93) and longer time to recurrence when compared to tamoxifen, though the magnitude of the absolute difference was small. Additionally, the MA-17 study showed that letrozole also offers minor but statistically significant advantages in extended therapy, i.e., beyond 5 years of adjuvant therapy. The International Examestate Study (IES) included 4,742 women who received examestane or tamoxifen after 2-3 years with adjuvant tamoxifen. After a 31 month follow-up median, the absolute difference favoring AIs for disease-free survival was 4.7%, with no changes in global survival. Adverse effects and limitants to clinical use: Toxicity profiles for the three more studied AIs: anastrazole, letrozole and examestane are similar. In general, they are associated to higher rates of hot flushes, arthralgia, myalgias, osteoporosis and bone fractures and with a lower rate of vaginal bleeding and thromboembolic events than with placebo. They do not present the harmful effects on the endometrium which tamoxifen has.Some cost-effectiveness studies based on economic models have shown that the use of anastrozole results in a moderate increase in the cost for year of life saved when compared with tamoxifen. Other studies based on sensitivity analysis for first-line letrozole show that this drug is a marginally cost-effective alternative in the United Kingdom and in the United States. There are no cost-efficiency studies in Argentina. These drugs are nowadays 10 times more expensive in our country than tamoxifen, and the clinical impact on their long-term adverse effects (specially osteoporosis) is not completely established. Currently, they are covered by some social security agencies as an alternative for women with symptomatic intolerance or contraindication to tamoxifen.