MonarchE Meets Primary End Point with Abemaciclib Combo in HR+, HER2- Breast Cancer

The combination of abemaciclib (Verzenio) and standard adjuvant endocrine therapy led to a significant decrease in the risk of breast cancer recurrence or death compared with adjuvant endocrine therapy alone in patients with hormone receptor (HR)-positive, HER2-negative early breast cancer, meeting the primary end point of invasive disease-free survival (iDFS) in the phase 3 monarchE study (NCT03155997), announced abemaciclib developer Eli Lilly and Company.

Based on the activity observed in this study, abemaciclib is the only CDK4/6 inhibitor to achieve a statistically significant reduction in the risk of recurrence in this patient population. The safety profile observed with abemaciclib plus standard adjuvant endocrine therapy in this study was consistent with prior studies in the MONARCH clinical program. Detailed results from this study will be presented at a medical meeting later in 2020.

"When a person is diagnosed with high-risk early-stage breast cancer, they strive to do everything in their power to prevent a recurrence. And as clinicians, we have the same goal," said Maura Dickler, MD, vice president of Oncology, Late-Phase Development, Lilly Oncology. "monarchE was intentionally designed for people whose breast cancer is at a high risk of returning. We are incredibly excited by the results of monarchE and that we can potentially offer a new treatment option for patients with high-risk HR-positive, HER2-negative early breast cancer."

MonarchE is a phase 3 multicenter, randomized, open-label clinical trial. A total of 5637 patients with high-risk node-positive, HR-positive, HER2-negative breast cancer have been enrolled in the study. Randomization was carried out in a 1:1 fashion, and those who were randomized to the abemaciclib arm received a 150 mg dose twice daily in combination with standard adjuvant endocrine therapy.

Treatment with abemaciclib in monarchE is continued for 2 years or until patients meet the discontinuation criteria. Standard endocrine therapy is administered for a minimum of 5 years if it is considered to be medically appropriate. In addition to the primary end point of iDFS, the study is also investigating distant relapse-free survival, overall survival, safety, pharmacokinetics, and health outcomes.

In the study, investigators classified patients as high risk based on features like having 4 or more pathologically positive axillary lymph nodes (pALNs) or 1 to 3 pathological pALNs with a high-risk feature such as primary invasive tumor size of at least 5 cm, histological grade 3 tumor, or central Ki-67 index of 20% or greater. Patients were required to also have completed adjuvant chemotherapy and radiotherapy, if applicable, before they could enroll in the study. Any acute side effects had to be resolved before patients can enroll.

Abemaciclib, a CDK4/6 inhibitor, is indicated for the treatment of patients with HR-positive, HER2-negative advanced or metastatic breast cancer. It is also indicated in combination with an aromatase inhibitor for the treatment of postmenopausal women as initial endocrine-based therapy,in combination with fulvestrant for women with disease progression following endocrine therapy, and as monotherapy for the treatment of adult patients with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

_Reference:

_{Verzenio® (abemaciclib) significantly reduced the risk of cancer returning in people with high risk hr+, her2- early breast cancer. News release. Eli Lilly and Company. June 16, 2020. Accessed June 16, 2020. https://bit.ly/3fv2fq8.}