Eli Lilly announced positive topline results from the primary overall survival analysis of its Phase 3 monarchE trial, demonstrating that two years of treatment with Verzenio (abemaciclib) plus endocrine therapy significantly improved overall survival compared to endocrine therapy alone in patients with hormone receptor positive (HR+), HER2-, node-positive, high-risk early breast cancer.
The seven-year landmark analysis also demonstrated sustained benefit in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS), reinforcing the consistency and durability of treatment effect across endpoints. According to Jacob Van Naarden, executive vice president and president of Lilly Oncology, "Preventing disease relapse and helping patients live longer is the ultimate goal and a high bar in the adjuvant setting. Achieving a statistically significant OS benefit with just two years of Verzenio therapy reinforces its differentiated profile in high-risk HR+, HER2- early breast cancer."
Study Design and Patient Population
The monarchE study was a global, randomized, open-label, two cohort, multicenter Phase 3 clinical trial that enrolled 5,637 adults with HR+, HER2-, node-positive early breast cancer at high risk of recurrence. The study enrolled patients across more than 600 sites in 38 countries and is the only adjuvant study designed to investigate a CDK4/6 inhibitor specifically in a node-positive, high risk early breast cancer population.
To be enrolled in Cohort 1 (n=5,120), which represents the FDA-approved population, patients had to have 4+ positive nodes or 1-3 positive nodes and at least one of the following: tumors that were ≥5 cm or Grade 3. Patients enrolled in Cohort 2 (n=517) had to have 1-3 positive nodes and Ki-67 score ≥20%. Patients in each cohort were randomized 1:1 to receive either Verzenio 150 mg twice daily plus standard-of-care adjuvant endocrine therapy or standard-of-care adjuvant endocrine therapy alone for 2 years.
Clinical Significance and Safety Profile
The overall survival analysis plan was amended after the primary analysis of IDFS, following consultation with regulators, to increase the number of required OS events from 390 to 650 to ensure a minimum follow-up of at least 5 years and enable a more mature survival dataset. With all patients having completed or discontinued the two-year course of Verzenio, the overall safety profile was unchanged and consistent with previous reports.
High risk patients with HR+, HER2- early breast cancer are three times more likely than those with low risk characteristics to experience recurrence, with the majority being incurable metastatic disease. These patients have an increased risk of recurrence during the first two years of endocrine therapy. Factors associated with high risk of recurrence include positive nodal status, the number of positive nodes, large tumor size (≥5 cm), and high tumor grade (Grade 3).
Market Impact and Competitive Landscape
Verzenio has become one of Lilly's top-sellers, bringing in sales of $5.3 billion last year. The drug became the first CDK4/6 inhibitor approved to treat node-positive, high risk early breast cancer patients, backed by the primary results from the monarchE study. The National Comprehensive Cancer Network (NCCN) recommends consideration of two years of abemaciclib (Verzenio) added to endocrine therapy as a Category 1 treatment option in the adjuvant setting.
While Pfizer and Novartis both sell rival CDK 4/6 inhibitors, Novartis has had success with its drug Kisqali, which in 2023 showed it could reduce the risk of cancer returning in people with HR+, HER2- breast cancer when used after surgery. However, Novartis' trial included participants whose cancer had not yet spread to the lymph nodes, while monarchE enrolled people whose cancer had spread to lymph nodes.
Disease Burden and Treatment Context
Breast cancer is the second most commonly diagnosed cancer worldwide, with an estimated 2.3 million new cases indicating that close to 1 in every 4 cancers diagnosed in 2022 is breast cancer. With approximately 666,000 deaths in 2022, breast cancer is the fourth-leading cause of cancer death worldwide. In the U.S., it is estimated that there will be more than 310,000 new cases of breast cancer diagnosed in 2024.
It is estimated that 90% of all breast cancers are detected at an early stage, and approximately 70% of all breast cancer cases are the HR+, HER2- subtype. Although the prognosis for HR+, HER2- early breast cancer is generally favorable, high risk patients face significantly increased recurrence rates.
Detailed results from the monarchE overall survival analysis will be presented at a future medical meeting, submitted for publication in a peer-reviewed journal and discussed with regulatory bodies.
