Abstract OT2-6-09: 4EVER - A phase IIIb, multi-center, open label study for postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer (BC) treated with everolimus (EVE) in combination with exemestane (EXE)

Abstract BACKGROUND The double blind, placebo-controlled BOLERO-2 trial demonstrated a significant doubling of progression free survival (PFS) with EVE and EXE compared to EXE alone for postmenopausal women with hormone-receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) BC after recurrence/progression on non-steroidal aromatase inhibitors (NSAI) (Baselga J, et al. NEJM. 2012). The 4EVER study further evaluates the combination of EVE+EXE in a broader population to obtain greater insights and presents an extensive exploratory translational research program. SPECIFIC AIMS/TRIAL DESIGN 4EVER is a German multi-center, open-label, single-arm trial. 300 patients will receive EVE (10 mg/d)+EXE (25 mg/d) within clinical practice. The primary objective is to assess the overall response rate (ORR), the secondary objectives include PFS, overall survival, safety, quality of life (QoL), health utilities and health care resources. The exploratory biomarker objectives include pharmacogenetics, bone-turnover biomarkers, presence and molecular characteristics of circulating tumor cells, correlation of response to EVE+EXE with proteomics, and the influence of age, performance status, cancer activity and inflammation on anxiety and depression. Exploratory biomarkers are assessed at baseline and after 4, 12, and 24 weeks of treatment. ELIGIBILITY CRITERIA: Main inclusion criteria are postmenopausal women with metastatic or locally advanced ER+, HER2- BC, not amenable to curative treatment by surgery or radiotherapy, refractory to NSAI and with at least one lesion that can be accurately measured or bone lesions lytic or mixed (lytic+sclerotic) in the absence of measurable disease. STATISTICAL METHODS/TARGET ACCRUAL: The study is designed as an open-label, single-arm, phase IIIB trial to assess the efficacy and safety of EVE plus EXE in postmenopausal women with hormone receptor positive breast cancer progressing following prior therapy with NSAI. The primary objective is to estimate the ORR. Therefore, no statistical hypothesis or model is underlying the analysis. The ORR, i.e. best overall response of complete response (CR) or partial response (PR), as well as individual response categories CR, PR, stable disease (SD), progressive disease (PD) or unknown will be summarized using frequency tables together with their associated two-sided exact 95% confidence intervals (Clopper-Pearson method). The full analysis set will be used for the primary efficacy analysis. The primary efficacy and safety analysis will be conducted on all patient data at the time all patients who are still receiving study drug will have completed at least 24 weeks of treatment (or discontinued prematurely). The study plans to randomize 300 patients over a 1-year accrual period. The expected trial duration from activation to reporting of ORR is about 2 years. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT2-6-09.