eMonarcHER: A phase 3 study of abemaciclib plus standard adjuvant endocrine therapy in patients with HR+, HER2+, node-positive, high-risk early breast cancer.

person Sara M. Tolaney Dana-Farber Cancer Institute, Boston, MA info_outline Sara M. Tolaney, Lesley Fallowfield, Peter A. Kaufman, Eva M. Ciruelos, Mary Corona Gainford, Yi Lu, Karla Hurt, Heather Ann Wasserstrom, Yanyun Chen, Shom Goel

Authors person Sara M. Tolaney Dana-Farber Cancer Institute, Boston, MA info_outline Sara M. Tolaney, Lesley Fallowfield, Peter A. Kaufman, Eva M. Ciruelos, Mary Corona Gainford, Yi Lu, Karla Hurt, Heather Ann Wasserstrom, Yanyun Chen, Shom Goel Organizations Dana-Farber Cancer Institute, Boston, MA, University of Sussex, Brighton, United Kingdom, University of Vermont Medical Center and the Larner College of Medicine at UVM, Burlington, VT, University Hospital 12 de Octubre, Madrid, Spain, Sanofi Genzyme:*Former employee of Eli Lilly and Company, Boston, MA, Eli Lilly and Company, Indianapolis, IN, Peter MacCallum Cancer Centre, Melbourne, Australia Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Eli Lilly and Company. Background: Hormone receptor positive (HR+), human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) with high-risk characteristics has a high risk of disease recurrence. Novel therapeutic options for this population are urgently needed. Abemaciclib is an oral, selective, and potent CDK4 & 6 inhibitor administered on a continuous schedule which is approved for HR+, HER2- advanced BC (ABC) as monotherapy and in combination with endocrine therapy (ET). Abemaciclib combined with ET demonstrated a statistically significant improvement in invasive disease-free survival (IDFS) in participants (pt) with HR+, HER2-, node-positive, high risk early breast cancer (EBC) and also clinical activity in HR+, HER2+ ABC. The eMonarcHER trial investigates whether abemaciclib plus ET will improve IDFS in pts with HR+, HER2+, node-positive, high risk EBC. Methods: eMonarcHER is a phase 3 global, randomized, double-blinded, placebo (PB)-controlled trial in participants with HR+, HER2+, node-positive, high risk EBC who have completed adjuvant HER2-targeted therapy (tx). Eligible participants are randomized 1:1 to receive either abemaciclib 150 mg twice daily or PB, plus standard ET. Study intervention period will be ≤26 cycles (approximately 2 years) followed by ≤8 years of ET as medically indicated. Participants must have undergone definitive surgery of the primary breast tumor and have high-risk disease. High-risk disease is defined as (i) detection of residual axillary nodal disease at the time of definitive surgery in participants with prior neoadjuvant (neoadj) tx; or (ii) in patients not receiving neoadj tx, must have either ≥4 pathologically positive axillary lymph nodes (pALNs), or 1-3 pathological pALNs and either: histologic Grade 2-3 and/or primary invasive tumor size ≥5 cm. Participants must have received either adjuvant pertuzumab plus trastuzumab with chemotherapy or adjuvant T-DM1. Stratification factors include treatment with neoadj tx, menopausal status, and region. The study is powered at approximately 80% to detect the superiority of abemaciclib plus ET over PB plus ET in terms of IDFS (as defined by the STEEP system) at a 1-sided α =.025 using a log-rank test. Assuming a hazard ratio of 0.73, this requires approximately 324 events at final IDFS analysis. Key secondary objectives include overall survival, distant relapse free survival, safety, pharmacokinetics, and patient-reported outcomes. The study is planned to start in March 2021. Approximately 525 centers in 23 countries plan to enroll ̃2450 participants. Clinical trial information: NCT04752332