Abemaciclib, an oral, selective inhibitor of CDK4/6 dosed on a twice-daily, continuous schedule, has demonstrated clinical efficacy and tolerability in patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer when administered as monotherapy (MONARCH 1) and in combination with endocrine therapy (ET) in MONARCH 2 and MONARCH 3.1-3 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.4 Endocrine monotherapy is the current standard of care in the adjuvant setting. However, relapse occurs among a proportion of patients despite this therapy. A population with a higher risk for recurrence (15% at 5 years) may be identified based on the clinical and pathologic characteristics of disease. Thus, optimizing adjuvant therapy for these patients is an important clinical need.
MonarchE (NCT03155997) is a multicenter, randomized, open-label phase 3 trial that will evaluate the potential for abemaciclib to enhance adjuvant ET.5 Patients will be randomized 1:1 to an abemaciclib 150-mg twice-daily continuous schedule plus standard of care (SOC) adjuvant ET versus SOC adjuvant ET alone, and will be stratified by prior chemotherapy (neoadjuvant, adjuvant, or none), menopausal status (pre- or post-), and region (North America/Europe, Asia, or other). Patients may have started ET within 8 weeks prior to randomization, and will receive abemaciclib for up to 2 years in combination with ET (such as tamoxifen or an aromatase inhibitor, ± ovarian suppression, per physician’s choice). ET alone will be continued as clinically indicated. All randomized patients will be followed for a total of 10 years. Eligible patients (male or female) must have early-stage, resected HR-positive/HER2-negative, invasive breast cancer with either ≥4 positive pathologic axillary lymph nodes (pALNs), or 1 to 3 positive pALNs and ≥1 of the following high-risk markers: primary tumor size ≥5, histologic grade 3 tumor, or centrally assessed Ki67 index of ≥20% (in a subset of patients), and must have completed definitive locoregional therapy (± [neo]adjuvant chemotherapy) and be randomized ≤12 weeks after completion of last non-ET (surgery, chemotherapy, or radiotherapy). Patients must have tumor tissue available for biomarker analysis prior to randomization.
The primary objective of MonarchE is to evaluate invasive disease-free survival (IDFS) per the STEEP System.6 Secondary objectives include evaluation of IDFS in patients with Ki67 index ≥20%, distant relapse-free survival, overall survival, safety, pharmacokinetics, and patient health outcomes. Target accrual for the trial is approximately 3580 patients.
References
To sign up for our newsletter or print publications, please enter your contact information below.