Phase III randomized, placebo-controlled clinical trial evaluating the use of adjuvant endocrine therapy with or without one year of everolimus in patients with high-risk, hormone receptor- (HR) positive and HER2-neu-negative breast cancer: SWOG/NSABP S1207.

Abstract

TPS657 Background: Abnormalities of the PI3kinase/AKT/mTOR signaling pathway are common in breast cancer. This pathway has been associated with endocrine resistance. Everolimus, an mTOR-inhibitor, has been shown to increase the biological activity endocrine therapies. S1207 proposes to evaluate the role of everolimus in combination with endocrine therapy in the adjuvant setting. Methods: S1207 is randomized phase III double-blinded, placebo-controlled clinical trial. The primary objective is to assess whether the addition of one year of everolimus to standard adjuvant endocrine therapy improves DFS. Secondary objectives include OS, DRFS, safety, adherence, and quality of life. Submission of tissue specimens/blood samples is required. Patients will be randomly assigned to receive standard adjuvant endocrine therapy in combination with one year of everolimus (10 mg PO daily) or in combination with one year of matched placebo. Eligibility Criteria: Patients with histologically confirmed invasive breast cancer HR-positive and HER2-negative with a) node-negative disease with tumors >2cm and a recurrence score (RS) >25; b) 1-3 positive lymph nodes RS >25; c) >4 positive lymph nodes are eligible after they have completed adjuvant chemotherapy; d) Patients with >4 positive lymph nodes after neoadjuvant chemotherapy are also eligible. Patients must have completed surgery, chemotherapy, and radiation therapy (if indicated) before registration. Statistical methods/ target accrual: Parallel randomization design with equal allocation to the two treatment groups with stratification by 4 risk groups. All analyses are intent-to-treat. The study plans to randomize 3,500 patients over a 3.5-year accrual period. All patients will be followed for 10 years to assess survival and late adverse events. The first interim analysis would be after 39% of the expected events (n=295) have been observed or approximately 3.5 years after initiation of the study. Support: NCI U10-CA-37377, -12027, -69651; Breast Cancer Research Foundation; Novartis. Clinical trial information: NCT01674140.