USFDA broadens indication for Eli Lilly's Verzenio in HR+, HER2-, Node-Positive, High Risk Early Breast Cancer

This label expansion is supported by four-year data from the Phase 3 monarchE trial of adjuvant Verzenio in combination with ET, which showed a deepened benefit in invasive disease-free survival (IDFS) beyond the two-year treatment course with adjuvant Verzenio. The absolute difference in IDFS between treatment groups increased over time. At four years, 85.5% of patients remained recurrence-free with Verzenio plus ET, compared to 78.6% with ET alone, an absolute difference in IDFS of 6.9%. At two years and at three years, the absolute differences between treatment groups were 3.1% and 5.0%, respectively. The addition of Verzenio to ET reduced the risk of recurrence by 35% compared to ET alone (HR=0.653 [95% CI: 0.567-0.753]). There were no new safety findings, and overall results are consistent with the well-established safety profile for Verzenio. These four-year monarchE data were presented at the 2022 San Antonio Breast Cancer Symposium and simultaneously published in The Lancet Oncology.

The monarchE study enrolled 5,637 adults with high risk HR+, HER2-, node-positive EBC into two cohorts. Verzenio is now approved for use in the full Cohort 1 patient population, which comprised 91% of the study population. A statistically significant difference in IDFS was observed in the intent-to-treat (ITT) population, primarily due to patients in Cohort 1. As of the data cut-off date, while overall survival (OS) data remain immature across the entire study, an OS trend in favor of Verzenio was observed in the Cohort 1 population, but not the Cohort 2 population where more deaths were seen with Verzenio plus ET compared to ET alone (10/253 vs. 5/264). 

"Our goal in intensifying treatment for early breast cancer is to maintain remission and prevent the recurrence of cancer. The magnitude of benefit seen in the four-year data from the monarchE study reinforces my confidence in adjuvant Verzenio as the standard-of-care for high risk patients in this setting," said Erika P. Hamilton, M.D., medical oncologist, director of Breast and Gynecologic Cancer Research at Sarah Cannon Research Institute, and an investigator on the monarchE clinical trial. "The initial Verzenio FDA approval in early breast cancer was practice-changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them."

More than 300,000 people are expected to be diagnosed with breast cancer in the U.S.in 2023. It is estimated that 90% of all breast cancers are detected at an early stage. Approximately 70% of all breast cancer cases are the HR+, HER2- subtype. Although the prognosis for HR+, HER2- EBC is generally favorable, high risk patients 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.

"This expanded approval will allow us to bring Verzenio to many more women and men with HR+, HER2-, high risk early breast cancer in the curative setting – before patients experience recurrence, potentially to incurable metastatic disease," said Jacob Van Naarden, chief executive officer of Loxo@Lilly. "The initial adjuvant approval for Verzenio changed the treatment paradigm, and the strength of the monarchE results supporting this approval underscores the role this differentiated CDK4/6 inhibitor can play in reducing the risk of recurrence in early breast cancer."

"This expanded approval for Verzenio is welcome news for our community," said Jean Sachs, chief executive officer of Living Beyond Breast Cancer. "A significant number of women and men have HR+, HER2- early breast cancer at high risk of returning. Making effective treatment options available is crucial to allowing people to make the best care decisions for themselves, together with their healthcare providers. We're pleased Verzenio will now be available to more people with this type of early breast cancer."

Concurrent with this expanded indication approval in EBC, the FDA has also broadened the indicated use of Verzenio in metastatic breast cancer (MBC) when used in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of people with HR+, HER2- advanced or MBC. This updated MBC indication now includes all adult patients, with the expanded indication including pre-/perimenopausal women when used in combination with ovarian suppression. Verzenio is available in tablet strengths of 50 mg, 100 mg, 150 mg, and 200 mg.

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