INDIANAPOLIS, Sept. 27, 2021 /PRNewswire/ -- New data from Eli Lilly and Company's (NYSE: LLY) monarchE study for an investigational use of Verzenio® (abemaciclib), in combination with endocrine therapy, in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2) high risk early breast cancer will be presented at the October 14European Society for Medical Oncology (ESMO) Virtual Plenary.

Details on this presentation are shared below.

The presentation will utilize an April 2021 data cutoff date, allowing for more follow-up relative to the analysis last presented at the San Antonio Breast Cancer Symposium in December 2020.

The abstract is embargoed until the start of the Virtual Plenary session. For more information, please visit: https://www.esmo.org/meetings/october-virtual-plenary-2021.

About the monarchE Study monarchE is a global randomized, open-label, Phase 3 study in women and men with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, early breast cancer at high risk of recurrence. High risk of recurrence was defined by disease characteristics: either ≥4 positive axillary lymph nodes (pALN) or 1-3 pALN and at least one of the following criteria: tumor size ≥5 cm, histologic Grade 3, or Ki-67 index ≥20%. Patients had completed definitive locoregional therapy.

A total of 5,637 patients were randomized in a 1:1 ratio to receive two years of Verzenio 150 mg twice daily plus physician's choice of standard endocrine therapy, or standard endocrine therapy alone. After the treatment period, all patients will continue on endocrine therapy for five to 10 years, as clinically indicated.

The study's primary endpoint is invasive disease-free survival (IDFS). Secondary endpoints include distant relapse-free survival (DRFS), IDFS for patients with Ki-67 index ≥20%, and overall survival (OS). 

Notes to Editors 

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 FOR VERZENIO

Verzenio is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer:

• in combination with an aromatase inhibitor for postmenopausal women as initial endocrine-based therapy
• in combination with fulvestrant for women with disease progression following endocrine therapy
• as a single agent for adult patients with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting

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