AS1402 + letrozole

AS1402 + letrozole is a combination therapy investigated for the treatment of hormone receptor-positive, locally advanced or metastatic breast cancer in postmenopausal women. AS1402 is a humanized immunoglobulin G1 monoclonal antibody that targets the aberrantly glycosylated antigen MUC1, which is overexpressed in approximately 90% of breast tumors and modulates estrogen receptor (ER) activity. Letrozole is an aromatase inhibitor that reduces estrogen production and is commonly used as endocrine therapy in ER-positive breast cancer. The rationale for combining these agents was based on preclinical evidence suggesting that targeting MUC1 could disrupt ER-mediated tumor growth and that aromatase inhibitors may enhance antibody-dependent cell-mediated cytotoxicity (ADCC). However, clinical trials showed no improvement in efficacy with the addition of AS1402 to letrozole compared to letrozole alone; development was discontinued due to lack of benefit[1][3][4].