Lilly’s CDK4/6 Inhibitor Abemaciclib Demonstrates Sustained Reduction in Recurrence Risk Over 5 Years in High-Risk Early Breast Cancer

▎Edited by the WuXi AppTec content team

Recently, Eli Lilly and Company announced at the European Society for Medical Oncology (ESMO) Congress the interim analysis results of overall survival (OS) and 5-year efficacy outcomes from the randomized, multicenter, Phase 3 clinical trial, monarchE, investigating abemaciclib (brand name: Verzenio) in combination with endocrine therapy (ET) as adjuvant treatment for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), high-risk early breast cancer. The trial results demonstrated,Abemaciclib combined with ET therapy can continuously reduce the risk of invasive and distant disease recurrence in early breast cancer, improving long-term outcomes for patients.

Breast cancer is the most common cancer among women worldwide.It is estimated that90% of breast cancers are diagnosed at an early stage.The most common subtype is HR+, HER2-, which accounts for approximately 70% of all breast cancer patients.About 30% of patients diagnosed with HR+, HER2- early breast cancer still have the risk of cancer recurrence. These patients need new treatment options.

Abemaciclib is an inhibitor of cyclin-dependent kinases (CDK) 4 and 6, activated by binding to cyclin D.It can inhibit the phosphorylation of Rb and block the progression of cells from the G1 phase to the S phase of the cell cycle, leading to cellular senescence and apoptosis.

monarchE is a randomized, open-label, two-cohort, multicenter global Phase 3 clinical trial, enrolling a total of 5,637 adult patients with HR+, HER2-, node-positive, high-risk early breast cancer with a higher risk of recurrence. Patients were randomly assigned 1:1 to receive either abemaciclib plus standard adjuvant endocrine therapy or standard adjuvant endocrine therapy alone. The intent-to-treat (ITT) population included Cohort 1 (5,120 patients) and Cohort 2 (517 patients). Investigators conducted a statistically significant test on overall survival in the ITT population.

The analysis results show that,In the ITT population with a median follow-up of 54 months, abemaciclib treatment demonstrated sustained benefit.The hazard ratio (HR) for invasive disease-free survival (IDFS) was 0.680 (95% CI: 0.599, 0.772), and the HR for distant relapse-free survival (DRFS) was 0.675 (95% CI: 0.588, 0.774).The persistence of abemaciclib treatment benefits translates into a sustained separation of survival curves (KM curves), with absolute improvement rates of 7.6% and 6.7% for 5-year IDFS and DRFS, respectively.The absolute improvement rates for 4-year IDFS/DRFS were 6.0%/5.3%, and for 3-year IDFS/DRFS, they were 4.8%/4.1%. The treatment benefits in Cohort 1 were consistent with ITT. No new safety signals were observed in the trial. Compared with the ET treatment group,The number of deaths in the abemaciclib plus ET treatment group remained lower (208 vs 234; HR 0.903; p=0.284), but did not reach statistical significance.

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Based on these findings, the researchers believe that,During the critical 5-year period of adjuvant therapy trials for early breast cancer, abemaciclib combined with ET therapy can continue to reduce the risk of invasive and distant disease recurrence after treatment ends.The absolute improvement rate of efficacy continues to increase after 5 years., which is consistent with the sustained effect of the treatment and further supports the use of abemaciclib in patients with high-risk early breast cancer. The change in OS data favors the abemaciclib treatment group, and follow-up for the current trial is still ongoing.