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.
- Dickler MN, et al. Clin Cancer Res. 2017;23:5218-5224.
- Sledge GW Jr, et al. J Clin Oncol. 2017;35:2875-2884.
- Goetz MP, et al. J Clin Oncol. 2017;35:3638-3646.
- Hurvitz MM, et al. SABCS 2017. Abstract PD5-01.
- Rastogi P, et al. SABCS 2017. Abstract OT3-05-05.
- Hudis CA, et al. J Clin Oncol. 2007;25:2127-2132.