Abemaciclib ( Verzenio ) in combination with standard adjuvant endocrine therapy has met the primary endpoint of invasive disease-free survival ( IDFS ), significantly decreasing the risk of breast cancer recurrence or death compared to standard adjuvant endocrine therapy alone.
These results are from a pre-planned interim analysis of the phase 3 monarchE study.
Abemaciclib is the only CDK4 & 6 inhibitor to demonstrate a statistically significant reduction in the risk of cancer recurrence for people with high risk hormone receptor-positive ( HR+ ), human epidermal growth factor receptor 2-negative ( HER2- ) early breast cancer.
The safety profile was consistent with that observed in other studies with Abemaciclib in the MONARCH clinical program.
Despite progress in the treatment of breast cancer, approximately 30% of people diagnosed with HR+, HER2- early breast cancer are at risk of their cancer returning. This risk of recurrence increases based on certain clinical and/or pathological features such as breast cancer that has spread to the lymph nodes, a larger tumor size and a higher tumor grade.
New treatment options are needed to advance the field and help prevent early breast cancer from returning, potentially to an incurable metastatic stage.
Now Abemaciclib in combination with endocrine therapy has demonstrated positive results in people with high risk HR+, HER2- early breast cancer.
These results were achieved early, at the interim analysis.
The monarchE trial will continue through the completion date, estimated for June 2027.
At the time of the interim analysis, the IDFS results are considered definitive. All patients on the monarchE trial will be followed until primary analysis and beyond to assess overall survival and other endpoints.
monarchE is a phase 3, multicenter, randomized, open-label trial that enrolled 5,637 patients with high risk, node positive, HR+, HER2- early breast cancer.
Patients were randomized 1:1 to Abemaciclib ( 150 mg twice daily ) plus standard adjuvant endocrine therapy or standard adjuvant endocrine therapy alone.
Patients on the Abemaciclib arm receive treatment for up to two years or until discontinuation criteria are met. All patients receive standard endocrine therapy for at least 5 years if deemed medically appropriate.
The primary objective is invasive disease-free survival, which in monarchE is defined as the length of time before any cancer comes back or death. Secondary objectives include distant relapse-free survival, overall survival, safety, pharmacokinetics and health outcomes.
High risk was specifically defined as women ( any menopausal status ) and men with resected HR+, HER2- invasive early breast cancer with either greater than or equal to 4 pathologically positive axillary lymph nodes ( pALNs ) or 1 to 3 pathological pALNs with at least one of the following high-risk features: primary invasive tumor size greater than or equal to 5 cm, histological grade 3 tumor, or central Ki-67 index greater than or equal to 20%.
If applicable, patients must have also completed adjuvant chemotherapy and radiotherapy prior to enrolling and have recovered from all acute side effects.
Breast cancer is the most common cancer among women worldwide. An estimated 90% of all breast cancer is diagnosed at an early stage. Approximately 70% of all breast cancers are HR+, HER2-, the most common subtype.
Even within this subtype, HR+, HER2- breast cancer is a complex disease, and many factors, such as if the cancer has spread to the lymph nodes and the biology of the tumor, can impact the risk of recurrence.
Approximately 30% of people diagnosed with HR+, HER2- early breast cancer are at risk of their cancer returning, potentially to incurable metastatic disease.
Abemaciclib is an inhibitor of cyclin-dependent kinases ( CDK )4/6, which are activated by binding to D-cyclins. In estrogen receptor-positive ( ER+ ) breast cancer cell lines, cyclin D1 and CDK4/6 promote phosphorylation of the retinoblastoma protein ( Rb ), cell cycle progression, and cell proliferation.
In vitro, continuous exposure to Abemaciclib inhibites Rb phosphorylation and blocks progression from G1 to S phase of the cell cycle, resulting in senescence and apoptosis ( cell death ).
Preclinically, Abemaciclib dosed daily without interruption has reduced tumor size.
Inhibiting CDK4/6 in healthy cells can result in side effects, some of which may be serious.
Clinical evidence has also suggested that Abemaciclib crosses the blood-brain barrier. In patients with advanced cancer, including breast cancer, concentrations of Abemaciclib and its active metabolites ( M2 and M20 ) in cerebrospinal fluid are comparable to unbound plasma concentrations.
Verzenio is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer: in combination with an aromatase inhibitor for postmenopausal women as initial endocrine-based therapy; in combination with Fulvestrant for women with disease progression following endocrine therapy; as a single agent for adult patients with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting. ( Xagena )
Source: Lilly, 2020