Lilly Announces Updated Data for Verzenio® (abemaciclib) as the First and Only CDK4/6 Inhibitor Approved for High-Risk HR+/HER2- Early Breast Cancer

October 23, 2021 /BIOONBIOON/ --Eli Lilly(Eli Lilly) recently announced updated data from the Phase III monarchE trial. The trial is evaluating the targeted anticancer drug Verzenio (Chinese brand name: Wei Ze®, generic name: abemaciclib tablets) in combination with standard adjuvant endocrine therapy (ET) for the treatment of HR+/HER2-, node-positive, high-risk early-stageBreast cancer(EBC) patients. Updated data have been presented at the ESMO virtual plenaryConferencepublished on, and simultaneously published in 《TumorAnnals of Oncology》. For details, see:Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study。

As previously mentioned in 《ClinicalTumordata published in the Journal of Clinical Oncology (JCO),The monarchE trial met its primary endpoint: in the intent-to-treat (ITT) population, compared with the ET treatment group, the Verzenio + ET treatment group demonstrated a statistically significant improvement in invasive disease-free survival (IDFS).

This trial included female and male patients with HR+/HER2– lymph node–positive EBC who were at high risk of disease recurrence based on clinical and pathological features (N=5637). In the trial, patients were assigned to one of two cohorts. Cohort 1 enrolled patients with ≥4 positive axillary lymph nodes (ALNs), or 1–3 positive ALNs and either grade 3 disease orTumorSize ≥5 cm. Patients enrolled in Cohort 2 with 1–3 positive ALNs and a centrally assessed Ki-67 score ≥20% (defined as "high Ki-67" in the study).Ki-67 is a marker of cell proliferation.Ki-67 scores were also centrally assessed in patients in Cohort 1 with adequate samples; however, Ki-67 assessment was not required for enrollment in this cohort. The ITT population included Cohort 1 and Cohort 2.

The updated data released include the latest results reflecting a median follow-up of 27 months. In the latest analysis, the benefits of Verzenio for IDFS and distant relapse-free survival (DRFS) were sustained (Table 1 below).At 3 years, the absolute improvement rates for IDFS and DRFS were 5.4% and 4.2%, respectively.Furthermore, an exploratory piecewise analysis of the annual hazard ratio (HR) estimates for IDFS and DRFS was conducted. The results indicated that the magnitude of the treatment effect on IDFS increased over time: from the first year (0–1 year HR=0.80, 95% CI: 0.59, 1.03) to the second year (1–2 years HR=0.68, 95% CI: 0.52, 0.87), and continued to strengthen after the 2-year study treatment period (>2 years HR=0.60, 95% CI: 0.40, 0.86). Similarly, the HR estimates for DRFS also strengthened from the first year (0–1 year HR=0.73, 95% CI: 0.52, 0.99) to the second year (1–2 years HR=0.68, 95% CI: 0.51, 0.88), and persisted beyond the 2-year study treatment period (>2 years HR=0.69, 95% CI: 0.45, 1.03).

October 2021,The U.S. FDA has approved Verzenio in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with HR+/HER2- high-risk early breast cancer (EBC). Specifically: node-positive, high risk of recurrence, andFDAThe approved testing method is specified for HR+/HER2- EBC patients with a Ki-67 score ≥20%.Ki-67 is a marker of cell proliferation.

It is worth noting that,Verzenio is the first and only CDK4/6 inhibitor approved for the above patient population.。 In addition, in the treatment of HR+/HER2- EBC, Verzenio is the first in nearly two decadesFDAThe first drug approved for addition to adjuvant endocrine therapy. Data from the Phase III monarchE study demonstrated that, in patients with lymph node-positive, high-risk HR+/HER2- EBC, treatment with Verzenio in combination with ET resulted in a statistically and clinically significant reduction in the risk of disease recurrence compared with standard adjuvant endocrine therapy (ET).

This FDA approval builds upon the existing evidence for Verzenio, which was previously approved for the treatment of certain types of HR+/HER2- advanced or metastatic breast cancer. Along with this approval,FDAThe use of Verzenio has also been expanded across all indications to include male patients when used in combination with endocrine therapy (ET). Verzenio tablets are available in strengths of 200 mg, 150 mg, 100 mg, and 50 mg.

This approval is based on the efficacy analysis results from subgroups of the monarchE trial, as well as additional post hoc follow-up. In this analysis, Verzenio in combination with ET continued to demonstrate a clinically meaningful benefit: among patients with high-risk clinical and pathological features and a Ki-67 score ≥20%, Verzenio + ET reduced the risk of breast cancer recurrence or death by 37% compared with standard adjuvant ET (HR=0.626; 95% CI: 0.49–0.80), with an absolute benefit of 7.1% in the 3-year IDFS event rate. In this analysis, there were 104 IDFS events in the Verzenio + ET group compared with 158 in the ET group. Overall survival (OS) data remain immature, and further follow-up is ongoing. In this trial,Adverse ReactionsConsistent with the known safety profile of Verzenio.

Breast cancer is the most common cancer among women worldwide. An estimated 90% of breast cancers are at an early stage.Diagnosisof. 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.

The active ingredient of Verzenio is abemaciclib, an oral targeted CDK4/6 inhibitor that selectively inhibits cyclin-dependent kinase 4 and 6 (CDK4/6), restores cell cycle control, and blocksTumorCell Proliferation. Dysregulation of the cell cycle is a hallmark of cancer, and CDK4/6 is overactive in many cancers, leading to uncontrolled cell proliferation. CDK4/6 serves as a key regulator 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 prevalent, and CDK4/6 acts as a key downstream target of ER signaling. Preclinical data indicate that dual inhibition of CDK4/6 and ER signaling exerts a synergistic effect and can inhibit the growth of G1-phase ER+ breast cancer cells. Clinical evidence also demonstrates 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 the unbound plasma concentrations.

Verzenio was approved for marketing in October 2017 for the treatment of patients with HR+/HER2- advanced or metastatic breast cancer. It 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 with disease progression following 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 are commercially available, in addition toEli LillyIn addition to 's Verzenio, there are alsoPfizerof Ibrance (palbociclib) andNovartisof Kisqali (ribociclib). In China, Pfizer's Ibrance (Chinese trade name: Aiboxin, generic name: palbociclib) was approved in August 2018, becoming the first CDK4/6 inhibitor approved in China, with its indication being: in combination with an aromatase inhibitor, as initial endocrine-based therapy, for the treatment of postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer.

December 2020,Eli LillyVerzenio (Chinese trade name: Weize®, generic name: abemaciclib) has been approved, becoming the second CDK4/6 inhibitor approved in China,This drug is indicated for the treatment of HR+/HER2- locally advanced or metastatic breast cancer: (1) in combination with an aromatase inhibitor as initial endocrine therapy for postmenopausal women; (2) in combination with fulvestrant for patients whose disease has progressed following prior endocrine therapy.

March 8, 2021,Eli LillySimultaneous launch press conferences were held in Beijing and Shanghai: the CDK4/6 inhibitor Verzenio® (abemaciclib tablets) has been successfully launched in China. (Bioon.com)

Original Source:Lilly Announces Updated Verzenio® (abemaciclib) Phase 3 monarchE Trial Data Presented at ESMO Virtual Plenary and Simultaneously Published in the Annals of Oncology