Upfront vs. sequential aromatase inhibitors: An ongoing or settled debate?

Adjuvant hormonal therapy with an aromatase inhibitor has become a standard treatment option for post menopaual women with breast cancer. Compared to tamoxifen alone, upfront aromatase inhibitor and sequential tamoxifen-aromatase inhibitor strategies have been shown to improve the recurrence risk of breast cancer in a number of clinical trials. Despite the higher costs associated with aromatase inhibitors, compared to tamoxfien, both approaches have also been shown to be cost effective strategies with good value for money. As such, aromatase inhibitors are currently indicated as adjuvant hormonal therapy in post menopausal women with breast cancer considering their favorable clinical and economic profile. This chapter reviews the current evidence, from a clinical and an economic perspective, with regard to the preferred adjuvant strategy of aromatase inhibitor whether upfront or sequential treatment. The evolution of clinical evidence from indirect across studies analyses / modeling to the first results of a direct randomized study comparing both approaches is discussed. Economic evaluations based on indirect comparison across clinical studies are reviewed, and a direct head to head comparison based on BIG 1-98 study is presented.