Exemestane-everolimus in HER2-negative, hormonal receptor-positive, post-menopausal metastatic breast cancer with resistance to non-steroidal aromatase inhibitor: a new option

Phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is commonly deregulated in breast cancer and has been involved in resistance to endocrine therapy. In the BOLERO-2 study, the addition of everolimus, a selective inhibitor of mTOR protein, to exemestane was associated with a significant improvement in progression-free survival, compared to exemestane plus placebo, in patients with hormone receptor-positive, HER2-negative metastatic breast cancer, and resistant to non-steroidal aromatase inhibitor therapy. However, adverse events and treatment stops were more often observed with the combination therapy, suggesting the need for a careful benefit/risk evaluation before initiating this new combination. This review aims at synthesizing the biological basis of the everolimus-exemestane association, presenting the main validated and ongoing therapeutic trials, interests and limits, as well as the multiple potential therapeutic perspectives.