Table 6.

Key questions in ongoing clinical trials

Will the BOLERO-2 trial show an overall survival benefit favoring patients receiving everolimus combined with exemestane?

Is there a role for everolimus in the first-line treatment of estrogen receptor-positive HER2-negative advanced breast cancer not previously exposed to any endocrine therapy?

Should everolimus or a drug targeting the PI3K-AKT-mTOR pathway be part of the next or later line of treatment for tumors progressing while receiving a regimen containing an mTOR inhibitor?

Is there any role for everolimus in the adjuvant treatment of high-risk, early-stage estrogen receptor-positive, HER2-negative breast cancer?

Is there any overall survival benefit in the BOLERO-3 trial comparing trastuzumab, vinorelbine, and everolimus with trastuzumab, vinorelbine, and placebo in heavily pretreated HER2-positive advanced breast cancer?

Do we see a more pronounced absolute benefit in HER2-positive advanced breast cancer when everolimus is added to standard therapy in less heavily pretreated patients (BOLERO-1) compared with the outcome observed in the BOLERO-3 trial?

Will we see improved outcome compared with everolimus-based therapy using second-generation mTOR inhibitors?

Abbreviations: BOLERO, Breast cancer trials of OraL EveROlimus; HER2, human epidermal growth factor receptor 2; PI3K-AKT-mTOR, phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin.