Verzenio (abemaciclib): First CDK4/6 Inhibitor to Significantly Reduce Recurrence Risk in High-Risk HR+/HER2- Early Breast Cancer

December 10, 2020 /BioValleyBIOON/ --Eli Lilly(Eli Lilly) recently at the 2020 San AntonioBreast CancerAdditional data from the primary analysis of the Phase III monarchE study evaluating the targeted anticancer drug Verzenio (abemaciclib) for the treatment of breast cancer were presented at the online symposium (2020 San Antonio Breast Cancer Virtual Symposium): with a median follow-up of 19.1 months,Compared with standard adjuvant endocrine therapy (ET) compared with standard adjuvant ET alone, Verzenio in combination with standard adjuvant ET significantly reduced the risk of breast cancer recurrence by 28.7% (HR=0.713; 95% CI: 0.583, 0.871;p=0.0009）。

monarchE is a multicenter, randomized, open-label Phase 3 trial that enrolled 5,637 patients with high-risk HR+/HER2- early breast cancer (eBC) from more than 600 clinical sites across 38 countries worldwide. High risk was defined as cancer cells having spread to the lymph nodes, large tumor size, or high cellular proliferation (as determined byTumordetermined by grade or Ki-67 index). In the study, patients were randomized 1:1 to receive Verzenio (150 mg twice daily) in combination with standard adjuvant ET or standard adjuvant ET alone. Patients received treatment for 2 years (treatment period) or until discontinuation criteria were met. After the treatment period, all patients continued ET for 5–10 years.

Data presented at the conference showed that, with a median follow-up of 19.1 months, Verzenio combined with standard adjuvant endocrine therapy (ET) significantly reduced the risk of breast cancer recurrence by 28.7% compared to standard adjuvant ET alone (HR=0.713; 95% CI: 0.583–0.871; p=0.0009). This statistically significant improvement corresponded to a 3% difference in 2-year invasive disease-free survival (IDFS) between the two groups (92.3% in the Verzenio group vs. 89.3% in the control group). The data presented included an additional 3.6 months of follow-up beyond the pre-planned interim analysis announced in September 2020 (median follow-up of 15.5 months). Since the initiation of the study, more than 1,400 patients have completed 2 years of treatment.

Breast cancer is the most common cancer among women worldwide. It is estimated that 90% of breast cancers are detected at an early stage.Diagnosis. Approximately 70% of breast cancers are HR+/HER2-, which is the most common subtype. Even within the HR+/HER2- subtype, breast cancer is a complex disease, and many factors—such as whether the cancer has spread to the lymph nodes,TumorBiological characteristics—will all affect the risk of recurrence.

Despite advances in the treatment of breast cancer, approximately 30% of patients diagnosed with HR+, HER2- early-stage breast cancer are at risk of cancer recurrence, potentially progressing to incurable metastatic disease. Due to certain clinical and/or pathological features, such as the spread of breast cancer to lymph nodes and large tumor volume,TumorHigher grade is associated with an increased risk of cancer recurrence. New treatment regimens are needed to advance this field and help prevent recurrence of early-stage breast cancer, as well as progression to incurable metastatic disease.

The active pharmaceutical ingredient of Verzenios is abemaciclib, an oral targeted CDK4/6 inhibitor that selectively inhibits cyclin-dependent kinases 4 and 6 (CDK4/6), restoring cell cycle control and blockingTumorCell Proliferation. Dysregulation of the cell cycle is a hallmark of cancer, and CDK4/6 are overactive in many cancers, leading to uncontrolled cell proliferation. CDK4/6 are key regulators of the cell cycle, triggering the transition from the growth phase (G1 phase) to the DNA synthesis phase (S phase). In estrogen receptor-positive (ER+) breast cancer, CDK4/6 overactivity is highly frequent, as CDK4/6 are key downstream targets of ER signaling. Preclinical data demonstrate that dual inhibition of CDK4/6 and ER signaling has synergistic effects and can inhibit the growth of G1-phase ER+ breast cancer cells. Clinical evidence also indicates that abemaciclib crosses the blood-brain barrier. In patients with advanced cancer, including breast cancer, the concentrations of abemaciclib and its active metabolites (M2 and M20) in the cerebrospinal fluid are comparable to unbound plasma concentrations.

Verzenio was approved for marketing in October 2017 for the treatment of patients with HR+/HER2- advanced or metastatic breast cancer. The drug is indicated for: (1) use in combination with an aromatase inhibitor (AI) as initial endocrine therapy for postmenopausal women; (2) use in combination with fulvestrant for women whose disease has progressed on endocrine therapy; (3) use as monotherapy for adult patients with metastatic disease that has progressed after prior endocrine therapy and chemotherapy.

Currently, multiple CDK4/6 inhibitors have been marketed, in addition toEli Lillyin addition to Verzenio, there are alsoPfizerIbrance (palbociclib) andNovartisKisqali (ribociclib). (Bioon.com)

Original Source: Lilly Presents Positive Primary Outcome Data from monarchE that Builds on Previous Definitive Analysis for Verzenio®