MONARCH E: A phase 3 study of standard adjuvant endocrine therapy with or without abemaciclib in patients with high risk, node positive, hormone-receptor positive, human epidermal growth factor receptor 2-negative early-stage breast cancer

Background: Abemaciclib is an oral selective inhibitor of CDK 4 \u0026 6 administered on a continuous schedule and demonstrated clinically meaningful efficacy in patients with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer as monotherapy (MONARCH 1) and in combination with endocrine therapy (ET) in MONARCH 2 and MONARCH 3. Neoadjuvant abemaciclib + anastrozole (ANZ) (neoMONARCH) given for 2 weeks significantly reduced expression of Ki67 relative to ANZ alone. Endocrine monotherapy is the current endocrine standard of care (SOC) in the adjuvant setting, although risk of relapse remains a problem for patients with high-risk disease, identified by clinical and pathological characteristics of disease. Improving adjuvant therapy for patients with high-risk disease is an important need. Trial design: monarchE (NCT03155997) is a multicenter, randomized, open-label phase 3 trial evaluating adjuvant abemaciclib in patients with node-positive, high-risk, HR+, HER2- early advanced breast cancer. Patients are randomized 1:1 to abemaciclib 150 mg twice daily + SOC adjuvant ET vs SOC adjuvant ET alone and stratified by prior chemotherapy (neoadjuvant, adjuvant, or none), menopausal status (premenopausal or postmenopausal), and region (North America/Europe, Asia or Other). Patients in the investigation arm receive abemaciclib for up to 2 years or until discontinuation criteria are met. All patients receive ET for 5 years or as clinically indicated. Patients are followed for 10 years or until study completion, whichever comes first. The final evaluation for overall survival will mark study completion. Eligibility criteria: Patients must have early stage resected HR+, HER2- invasive advanced breast cancer with either ≥4 pathologically positive axillary lymph nodes (pALNs), or 1 to 3 pathological pALNs with at least one of the following high-risk factors: primary invasive tumor size ≥5 cm, histological grade 3 tumor, or central Ki67 index ≥20%. Patients must have completed definitive locoregional therapy (+/- [neo]adjuvant chemotherapy). Before randomization, patients may receive up to 12 weeks of ET after completing their last non-ET and must be randomized within 16 months of the definitive surgery. Specific aims: The primary objective is to evaluate invasive disease-free survival (IDFS) per the STEEP System.1 Secondary objectives include IDFS in patients with central Ki67 index ≥20%, distant relapse-free survival, overall survival, safety, pharmacokinetics, and health outcomes. Statistical methods: Assuming an IDFS hazard ratio of 0.73, the study is powered to ~85% to test the superiority of abemaciclib + standard ET at a 1-sided α=.025 using a stratified log-rank test. Target accrual: This study will be conducted in ~600 centers in 38 countries to enroll ~4580 patients. Accrual began in July 2017. Recruitment is complete. Contact information: 1-877-285-4559 Reference: 1. Hudis CA, Barlow WE, Costantino JP, et al. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007;25(15):2127-32. Citation Format: Priya Rastogi, Masakazu Toi, Miguel Martin, Joyce O9Shaughnessy, Desiree Headley, Jennifer Wei, Joanne Cox, Nadia Harbeck, Stephen Johnston. MONARCH E: A phase 3 study of standard adjuvant endocrine therapy with or without abemaciclib in patients with high risk, node positive, hormone-receptor positive, human epidermal growth factor receptor 2-negative early-stage breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-02-02.