Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2−, Node-Positive, High-Risk, Early Breast Cancer (monarchE)

Abstract

PURPOSE Many patients with HR+, HER2− early breast cancer (EBC) will not experience recurrence or have distant recurrence with currently available standard therapies. However, up to 30% of patients with high-risk clinical and/or pathologic features may experience distant recurrence, many in the first few years. Superior treatment options are needed to prevent early recurrence and development of metastases for this group of patients. Abemaciclib is an oral, continuously dosed, CDK4/6 inhibitor approved for HR+, HER2− advanced breast cancer (ABC). Efficacy and safety of abemaciclib in ABC supported evaluation in the adjuvant setting. METHODS This open-label, phase III study included patients with HR+, HER2−, high-risk EBC, who had surgery and, as indicated, radiotherapy and/or adjuvant/neoadjuvant chemotherapy. Patients with four or more positive nodes, or one to three nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%, were eligible and randomly assigned (1:1) to standard-of-care adjuvant endocrine therapy (ET) with or without abemaciclib (150 mg twice daily for 2 years). The primary end point was invasive disease-free survival (IDFS), and secondary end points included distant relapse–free survival, overall survival, and safety. RESULTS At a preplanned efficacy interim analysis, among 5,637 randomly assigned patients, 323 IDFS events were observed in the intent-to-treat population. Abemaciclib plus ET demonstrated superior IDFS versus ET alone ( P = .01; hazard ratio, 0.75; 95% CI, 0.60 to 0.93), with 2-year IDFS rates of 92.2% versus 88.7%, respectively. Safety data were consistent with the known safety profile of abemaciclib. CONCLUSION Abemaciclib when combined with ET is the first CDK4/6 inhibitor to demonstrate a significant improvement in IDFS in patients with HR+, HER2− node-positive EBC at high risk of early recurrence.

Update on the Management of Breast Cancer during Pregnancy

“…In luminal disease, recently, the addition of cycline-dependent kinase 4/6 inhibitors (CDK4/6i) abemaciclib to endocrine therapy showed promising results in the adjuvant setting for patients at a high risk of relapse leading to a potential role of these drugs in the early stage in next few years [65]. To date, no data on the safety of CDK4/6i during pregnancy are available, so currently their use is contraindicated during pregnancy.…”

Biomarkers for CDK4/6 inhibitor efficacy

“…Last month, Johnston et al confirmed the benefit of adjuvant CDK4/6 inhibitor therapy in combination with aromatase inhibitor therapy in the MonarchE adjuvant breast cancer clinical trial 5 . Nearly all of the targeted cancer therapies approved by the Federal Drug Administration in the last many years act by inhibiting driver oncogene activity.…”

“…Nearly all of the targeted cancer therapies approved by the Federal Drug Administration in the last many years act by inhibiting driver oncogene activity. MonarchE is the first adjuvant trial to demonstrate that targeted therapy thought primarily to act by replacing lost normal tumor suppressor gene activity—in this case Rb activity—can be effective in prolonging disease‐free survival 5 …”

Drug shows significant early promise in early, high‐risk, HR–positive, HER2–negative breast cancer

“…The trial's interim analysis was published in the Journal of Clinical Oncology 1 and also presented at the European Society for Medical Oncology Virtual Congress in September 2020. If the study's findings are confirmed in its final analysis, it will be the first time in more than 20 years that an advance has occurred in the adjuvant treatment of this form of breast cancer according to the lead author, Professor Stephen Johnston, MA, PhD, a medical oncologist with the Royal Marsden National Health Service Foundation Trust in London.…”