Preliminary Data from Ongoing Adjuvant Aromatase Inhibitor Trials¹

With recent results showing letrozole and anastrozole to be superior to tamoxifen as initial therapy for advanced disease, the aromatase inhibitors are poised to establish their place in the adjuvant therapy of postmenopausal receptor-positive breast cancer. A review of the rationale, design, and preliminary results of the ongoing adjuvant trials that include aromatase inhibitors will be presented, along with the ongoing or planned substudies. Two strategies employing aromatase inhibitors after tamoxifen are being evaluated. The MA.17 international intergroup trial is randomizing postmenopausal patients who are disease-free after 5 years of adjuvant tamoxifen to an additional 5 years of letrozole or placebo. In a similar design, the National Surgical Adjuvant Breast and Bowel Project (NSABP) B33 trial is randomizing this patient population to 2 years of exemestane or placebo after the standard 5 years of adjuvant tamoxifen. The second approach under study is the use of both aromatase inhibitor and tamoxifen in sequence within the first 5 post-operative years. The International Cancer Collaboration Group (ICCG) trial is comparing 2 years of exemestane after 3 years of tamoxifen to a standard 5-year course of tamoxifen. Similarly, the ARNO trial is comparing 5 years of tamoxifen versus 2 years of tamoxifen followed by 3 years of anastrozole. In a four-arm study Breast International Group/Femara-Tamoxifen (BIG/FEMTA) conducted by the BIG, one arm contains letrozole given for 3 years after 2 years of tamoxifen. Several trials are investigating the role of anastrozole, letrozole, or exemestane as a 5-year adjuvant therapy to replace the standard 5 years of tamoxifen. Only the Arimidex and Tamoxifen, Alone or in Combination (ATAC) trial is testing a 5-year combination of tamoxifen plus an aromatase inhibitor in this setting. Companion studies of effects on end-organs other than the breast are ongoing in a number of these trials. Aromatase inhibitors are poised to alter the treatment paradigm of breast cancer and hopefully improve outcome for a substantial number of patients.