BOLERO-2 trial demonstrated that the mTOR inhibitor everolimus was effective in overcoming resistance to endocrine therapy, and BOLERO-4 trial is evaluating the efficacy and safety of combined use of everolimus with letrozole as initial therapy for ER positive HER2 negative metastatic breast cancer (MBC). However, there is no study to evaluate the efficacy of everolimus which can prolong the administration period of aromatase inhibitor (AI) through postponing the acquisition of drug-resistance for MBC with sensitivity to aromatase inhibitor.
This study is conducted to examine whether additional administration of everolimus significantly prolongs progression-free survival period in post-menopausal patients with ER-positive HER2-negative MBC which have sensitivity to AI. The inclusion criteria are MBC pts with histologically confirmed ER positive and HER2 negative invasive breast cancer with one or more measurable distant metastatic lesions diagnosed by radiological examination. All patients are receiving AI as the first line hormone therapy for 5-7 months. The pts who are sensitive to AI are randomized to everolimus plus AI arm or the AI alone arm. After randomization, the same AI are continued until progression of diseases and next appropriate regimens are started after that. The primary endpoint is the progression free survival, and the secondary endpoints are overall survival, response rate, disease control rate, adverse events, time to treatment failure and the proportion of patients who continued administration of AI agents for 1 year after the randomized allocation. Sample size for randomized pts was determined to attain at least 80% of power to detect a 5.4 months’ difference (10 vs. 15.4 months, HR:0.65) with one-sided alpha of 0.1. Enrollment of 130 pts for randomization is planned over a 2-year accrual period from April 2017.
Clinical trial identification
This trial was registered at UMIN-CTR[umin.ac.jp/ctr/] as UMIN 000025156.
Legal entity responsible for the study
Comprehensive Support Project for Oncological Research of Breast Cancer
T. Toyama: Research funds from Novartis, Kyowa Hakko Kirin, Diichi Sankyo, Ezai, Chugai, Hippon Kayaku and Takeda Co. All other authors have declared no conflicts of interest.