Abstract OT3-05-05: MonarchE: A randomized, open-label, phase 3 study of abemaciclib combined with standard adjuvant endocrine therapy versus standard adjuvant endocrine therapy alone in patients with high risk, node positive, early stage, HR+, HER2- breast cancer
Authors: Rastogi P , Toi M , Harbeck N , Bourayou N , Frenzel M , Johnston S 
Published: February 2018

Abstract
Background: Abemaciclib, an oral, selective inhibitor of cyclin-dependent kinases 4 and 6 dosed on a twice daily continuous schedule, has demonstrated clinical efficacy and tolerability in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer when administered as monotherapy (MONARCH 1) and in combination with endocrine therapy (ET) in MONARCH 2 and MONARCH 3. In neoMONARCH, abemaciclib plus anastrozole as neoadjuvant therapy reduced the breast tumor cell proliferation marker Ki67 to a greater extent than anastrozole alone after 2 weeks of treatment. Endocrine monotherapy is the current standard of care in the adjuvant setting. However, a proportion of pts relapse despite this therapy. A population with a higher risk of recurrence (15% at 5 years) may be identified based on the clinical and pathological characteristics of disease. Optimizing adjuvant therapy for these pts is an important need.
Trial Design: MonarchE (NCT03155997) is a multicenter, randomized, open-label Phase 3 trial that will evaluate the potential for abemaciclib to enhance adjuvant ET. Pts will be randomized 1:1 to abemaciclib 150 mg twice daily continuous schedule plus standard of care (SOC) adjuvant ET versus SOC adjuvant ET alone and stratified by prior chemotherapy (neoadjuvant, adjuvant, or none), menopausal status (pre- or post-), and region (N. America/Europe, Asia, or other). Pts may have started ET within 8 weeks prior to randomization. Pts will receive abemaciclib for up to 2 years in combination with ET per physician's choice (such as tamoxifen or an aromatase inhibitor, +/- ovarian suppression). ET alone will be continued as clinically indicated. All randomized pts will be followed for a total of 10 years.
Eligibility Criteria: Eligible pts (male or female) must have early stage resected HR+, HER2- invasive breast cancer with either ≥ 4 positive pathological axillary lymph nodes (pALNs), or 1 to 3 positive pALNs and at least one of the following high risk markers: primary tumor size ≥5 cm, histological grade 3 tumor, or centrally assessed Ki67 index of ≥20% (in a subset of pts). Pts must have completed definitive locoregional therapy (+/- (neo)adjuvant chemotherapy) and be randomized no more than 12 weeks after completion of last non-ET (surgery, chemotherapy, or radiotherapy). Pts must have tumor tissue available for biomarker analysis prior to randomization.
Specific Aims: The primary objective of monarchE is to evaluate invasive disease-free survival (IDFS) per the STEEP System.1 Secondary objectives include evaluation of IDFS in pts with Ki67 index of ≥20%, distant relapse-free survival, overall survival, safety, pharmacokinetics, and pt health outcomes.
Statistical Methods: Assuming an IDFS hazard ratio of .73, the study is powered to approximately 80% to test the superiority of abemaciclib plus standard ET at a 1-sided α=0.025 using a stratified log-rank test.
Target accrual: Approximately 3580 pts
Contact information: 1-877-285-4559
Reference:
1. Hudis et al. J Clin Oncol. 2007;25(15):2127-2132.
Citation Format: Rastogi P, Toi M, Harbeck N, Bourayou N, Frenzel M, Johnston S. MonarchE: A randomized, open-label, phase 3 study of abemaciclib combined with standard adjuvant endocrine therapy versus standard adjuvant endocrine therapy alone in patients with high risk, node positive, early stage, HR+, HER2- breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-05-05.