Lilly’s Verzenio (abemaciclib) Plus Endocrine Therapy Reduces Breast Cancer Recurrence Risk by 38.6% in HR+/HER2- Early Breast Cancer Patients Following Neoadjuvant Chemotherapy
Jun 09, 2021 02:50
CST Updated
02:50
Eli Lilly
Global Pharmaceutical R&D and Production Company
June 9, 2021 News /BioonBIOON/ --Eli Lilly(Eli Lilly) recently announced the evaluation of the targeted anticancer drug Verzenio® (Chinese trade name: 唯择®, generic name: abemaciclib, abemaciclib tablets) in combination with standard adjuvant endocrine therapy (ET) versus standard adjuvant ET alone for the treatment of high-risk early-stage HR+/HER2-Breast cancer(EBC) Data from an exploratory analysis of the Phase III monarchE study. The results showed that,In the subgroup of patients with high-risk HR+/HER2- early breast cancer (EBC) who received neoadjuvant chemotherapy, the Verzenio + ET regimen reduced the risk of breast cancer recurrence by 38.6% compared with ET.
Breast cancer is the most common cancer among women worldwide. It is estimated that 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—all will affect the risk of recurrence.
Patients receiving neoadjuvant chemotherapy typically represent a population at very high risk of recurrence. New data from the monarchE trial further confirm this elevated risk, as a greater number of recurrence events occurred in the control arm within this subgroup. Given the need for new treatment approaches for high-risk EBC, particularly in the neoadjuvant population, these data are impressive and encouraging, demonstrating a 38% reduction in the risk of recurrence with the addition of Verzenio to standard ET.
March 8, 2021 (International Women's Day), Verzenio® officially launched in China!
monarchE is a multicenter, randomized, open-label phase 3 trial that enrolled 5,637 patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, high-risk early breast cancer (eBC) from more than 600 clinical sites across 38 countries worldwide. In the study, patients were randomized in a 1:1 ratio to two groups to receive either Verzenio (150 mg twice daily) in combination with standard adjuvant endocrine therapy (ET) or standard adjuvant ET alone. Patients received treatment for 2 years (the treatment period) or until meeting discontinuation criteria. Following the treatment period, all patients continued to receive ET for 5 to 10 years.
In an exploratory analysis, standard adjuvant ET plus Verzenio demonstrated a greater benefit in the prespecified subgroup of patients receiving neoadjuvant chemotherapy (n=2056) compared with the intention-to-treat (ITT) population (n=5673). This subgroup accounted for more than 36% of the total trial population, at the initialDiagnosisTimeTumorLarger in size and more commonly seen in premenopausal women,is the monarchE trialStrokeone of the patients in the highest-risk subgroup.
The specific data are as follows:Compared with standard adjuvant ET alone, Verzenio in combination with standard adjuvant ET reduced the risk of breast cancer recurrence by 38.6%.(HR = 0.614; 95% CI: 0.473–0.797). The difference in the 2-year invasive disease-free survival (IDFS) rate between the two treatment groups was 6.6% (87.2% for the Verzenio + ET group versus 80.6% for the ET group). Additionally,Compared with ET, Verzenio + ET reduced the risk of developing metastatic disease by 39% (HR=0.609; 95% CI: 0.459, 0.809).. The difference in the 2-year distant recurrence-free survival (DRFS) rate between the two treatment groups was 6.7% (89.5% for the Verzenio + ET group vs. 82.8% for the ET group). The safety data from this trial were consistent with the known safety profile of Verzenio, and no new safety signals were observed.
These data build upon the primary results of the Phase 3 monarchE trial: the trial met its primary endpoint at the second interim analysis, demonstrating a statistically significant improvement in iDFS. Compared with ET, Verzenio + ET reduced the risk of breast cancer recurrence by 28.7% (HR = 0.713; 95% CI: 0.583, 0.871; p = 0.0009), with an absolute difference of 3% in the 2-year IDFS and DRFS rates in the ITT population. The trial is ongoing and will continue to follow patients to assess safety, overall survival (OS), patient-reported outcomes, and other endpoints.
The active pharmaceutical ingredient of Verzenio is abemaciclib, an oral targeted CDK4/6 inhibitor that selectively inhibits cyclin-dependent kinase 4/6 (CDK4/6), restores cell cycle control, and blocksTumorCell Proliferation. Dysregulation of the cell cycle is a hallmark of cancer, with CDK4/6 being overactive in many cancers, leading to uncontrolled cell proliferation. CDK4/6 are key regulators of the cell cycle that drive the transition from the growth phase (G1 phase) to the DNA synthesis phase (S phase). CDK4/6 hyperactivity is highly prevalent in estrogen receptor-positive (ER+) breast cancer, and CDK4/6 serves as a key downstream target of ER signaling. Preclinical data demonstrate 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 indicates that abemaciclib penetrates 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) in combination with an aromatase inhibitor (AI) as initial endocrine therapy for postmenopausal women; (2) in combination with fulvestrant for women with disease progression following endocrine therapy; (3) as a single-agent therapy for adult patients whose metastatic disease was previously controlled by endocrine therapy and chemotherapy but has subsequently progressed.
Currently, multiple CDK4/6 inhibitors have been launched on the market, besidesEli LillyBesides Verzenio, there is also`Pfizer`of Ibrance (palbociclib) andNovartisof Kisqali (ribociclib). In China, Pfizer's Ibrance (Chinese trade name: Ai Bo Xin, generic name: palbociclib) was approved in August 2018, becoming the first CDK4/6 inhibitor approved in China. The indication for this drug is: in combination with an aromatase inhibitor as an initial endocrine 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. It 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 with disease progression following prior endocrine therapy.
March 8, 2021,Eli LillySimultaneous launch press conferences were held in Beijing and Shanghai: The CDK4/6 inhibitor Verzenio® (WEIZE®, abemaciclib tablets) has successfully launched in China. (Bioon.com)