BOLERO-4: Multicenter, open-label, phase II study of everolimus plus letrozole as first-line therapy in ER+, HER2- metastatic breast cancer.

TPS661 Background: Endocrine therapy (ET) is the standard of care for postmenopausal women with hormone receptor positive (HR+; typically, estrogen receptor [ER] positive) advanced breast cancer (ABC). However, women with HR+ ABC can progress while on ET. Crosstalk between ER signaling and the mammalian target of rapamycin (mTOR) pathway enhances tumor progression. Co-targeting these signaling pathways with the combination of everolimus (EVE), an orally bioavailable mTOR inhibitor, and ET (letrozole [LET] or tamoxifen) has been shown to significantly improve clinical outcomes in the neoadjuvant setting and in patients with HR+ ABC progressing on/after nonsteroidal aromatase inhibitors. In a pivotal phase 3 trial in women with HR+ ABC progressing on ET, EVE + exemestane (EXE) prolonged progression-free survival (PFS; local/central assessment: 7.8/11.0 mo [P u003c .0001]) compared with EXE alone (3.2/4.1 mo [P u003c .0001]). This study (BOLERO-4) will extend previous investigations to evaluate the safety and effect...