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INDIANAPOLIS, March 17, 2021 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced patient-reported outcomes (PRO) for the investigational use of Verzenio® (abemaciclib) in combination with standard adjuvant endocrine therapy (ET) for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) high risk early breast cancer (EBC). The PRO analysis included patients in both arms of the study and measured their experiences with side effects, symptoms, and health-related quality of life, in those receiving Verzenio plus ET versus ET alone. In one analysis, the PRO data indicated that most patients (approximately 70-75%) in both arms reported being bothered "a little bit" or "not at all" by treatment-related side effects. This analysis revealed the addition of Verzenio to ET did not result in a clinically meaningful difference in patients reporting being bothered by treatment side effects. The detailed data were presented at the virtual 17th St. Gallen International Breast Cancer Conference.
The data builds on the primary outcome analysis of the positive Phase 3 monarchE trial that previously showed Verzenio, in combination with ET, decreased the risk of breast cancer recurrence by 28.7 percent compared to ET alone – a statistically significant improvement in invasive disease-free survival for HR+, HER2- high risk early breast cancer (HR: 0.713; 95% CI: 0.583, 0.871; p = 0.0009).
"The patient-reported outcomes analysis represents another step forward in our understanding of the impact for patients who receive abemaciclib in the early breast cancer setting," said Dr. Sara M. Tolaney, MD, MPH, Harvard Medical School, Dana-Farber Cancer Institute. "These important data demonstrate actual patient-reported outcomes, which are the first to be reported for a CDK4 & 6 inhibitor in the early breast cancer setting. These analyses continue to reaffirm our confidence in abemaciclib, and its potential to make a difference for those with high risk early breast cancer."
PROs were assessed at randomization, during treatment (3 months onwards) and in the follow-up period (safety population, n=5591). Overall, patient compliance for PROs was greater than 90 percent. Expectedly, patient-reported diarrhea was more common in patients receiving Verzenio plus ET. Most patients who experienced diarrhea while receiving Verzenio plus ET reported having diarrhea "a little bit" or "somewhat." Health-related quality of life, patient-reported endocrine symptoms and fatigue, as well as patient responses to items reflecting hot flushes, arthralgia and fatigue were similar between treatment arms. With the exception of diarrhea, the addition of Verzenio to ET did not result in any clinically meaningful differences in the PROs. The PRO poster was selected for one of the three St. Gallen International Breast Cancer Conference Poster Awards 2021.
The monarchE trial is ongoing and patients will continue to be followed to assess safety, PROs and other endpoints. The abstracts presented at St. Gallen will be published in a supplement issue of The Breast, available on March 17, 2021. A list of the data presentations, along with the viewing details, are highlighted below.
Verzenio (abemaciclib):
About the monarchE StudymonarchE is a Phase 3, multicenter, randomized, open-label trial that enrolled 5,637 patients with HR+, HER2-, node-positive, high risk early breast cancer. Patients were randomized 1:1 to Verzenio (150 mg twice daily) plus standard adjuvant endocrine therapy or standard adjuvant endocrine therapy alone. Patients were treated for two years (treatment period) or until meeting criteria for discontinuation. After the treatment period, all patients will continue on endocrine therapy for five to 10 years, as clinically indicated. The primary objective is invasive disease-free survival (IDFS) defined according to the Standard Definitions for Efficacy Endpoints (STEEP) criteria. In adjuvant breast cancer trials, this includes the length of time before any cancer comes back, a new cancer develops 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 ≥4 pathologically positive axillary lymph nodes (ALNs) or 1 to 3 positive ALNs and at least one of the following high-risk features: primary invasive tumor size ≥5 cm, histological grade 3 tumor, or central Ki-67 index ≥20%. If applicable, patients must have also completed adjuvant chemotherapy and radiotherapy prior to enrolling and have recovered from all acute side effects.
About Early Breast CancerBreast cancer is the most common cancer among women worldwide.1 An estimated 90% of all breast cancer is diagnosed at an early stage.2 Approximately 70% of all breast cancers are HR+, HER2-, the most common subtype.3 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+ early breast cancer are at risk of their cancer returning, potentially to incurable metastatic disease.4
About Verzenio® (abemaciclib)Verzenio (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 Verzenio inhibited Rb phosphorylation and blocked progression from G1 to S phase of the cell cycle, resulting in senescence and apoptosis (cell death). Preclinically, Verzenio dosed daily without interruption resulted in reduction of tumor size. Inhibiting CDK4 & 6 in healthy cells can result in side effects, some of which may be serious. Clinical evidence also suggests that Verzenio crosses the blood-brain barrier. In patients with advanced cancer, including breast cancer, concentrations of Verzenio and its active metabolites (M2 and M20) in cerebrospinal fluid are comparable to unbound plasma concentrations.
Verzenio is Lilly's first solid oral dosage form to be made using a faster, more efficient process known as continuous manufacturing. Continuous manufacturing is a new and advanced type of manufacturing within the pharmaceutical industry, and Lilly is one of the first companies to use this technology.
INDICATION Verzenio is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer:
IMPORTANT SAFETY INFORMATION FOR VERZENIO (abemaciclib)
Diarrhea occurred in 81% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 86% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and 90% of patients receiving Verzenio alone in MONARCH 1. Grade 3 diarrhea occurred in 9% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 13% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and in 20% of patients receiving Verzenio alone in MONARCH 1. Episodes of diarrhea have been associated with dehydration and infection.
Diarrhea incidence was greatest during the first month of Verzenio dosing. In MONARCH 3, the median time to onset of the first diarrhea event was 8 days, and the median duration of diarrhea for Grades 2 and 3 were 11 and 8 days, respectively. In MONARCH 2, the median time to onset of the first diarrhea event was 6 days, and the median duration of diarrhea for Grades 2 and 3 were 9 days and 6 days, respectively. In MONARCH 3, 19% of patients with diarrhea required a dose omission and 13% required a dose reduction. In MONARCH 2, 22% of patients with diarrhea required a dose omission and 22% required a dose reduction. The time to onset and resolution for diarrhea were similar across MONARCH 3, MONARCH 2, and MONARCH 1.
Instruct patients that at the first sign of loose stools, they should start antidiarrheal therapy such as loperamide, increase oral fluids, and notify their healthcare provider for further instructions and appropriate follow-up. For Grade 3 or 4 diarrhea, or diarrhea that requires hospitalization, discontinue Verzenio until toxicity resolves to ≤Grade 1, and then resume Verzenio at the next lower dose.
Neutropenia occurred in 41% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 46% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and 37% of patients receiving Verzenio alone in MONARCH 1. A Grade ≥3 decrease in neutrophil count (based on laboratory findings) occurred in 22% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 32% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and in 27% of patients receiving Verzenio alone in MONARCH 1. In MONARCH 3, the median time to first episode of Grade ≥3 neutropenia was 33 days, and in MONARCH 2 and MONARCH 1, was 29 days. In MONARCH 3, median duration of Grade ≥3 neutropenia was 11 days, and for MONARCH 2 and MONARCH 1 was 15 days.
Monitor complete blood counts prior to the start of Verzenio therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.
Febrile neutropenia has been reported in
