FDA axes diagnostic requirement for Lilly's Verzenio + endocrine therapy in certain breast cancer patients
In the fall of 2021, when the FDA first authorized Eli Lilly’s CD4/6 inhibitor Verzenio plus endocrine therapy in early-stage HR-positive, HER2-negative breast cancer and at high risk of recurrence, the drug giant was limited in that patients had to have a Ki-67 score — a diagnostic test and staining technique that has been correlated to a worse prognosis in breast cancer patients — of at least 20%.
On Friday, FDA announced that the Ki-67 score requirement was lifted, expanding Lilly’s potential patient population.
The regulatory agency said the decision was based on results from the monarchE trial, the one that got Lilly the 2021 approval.
The trial enrolled thousands of patients into two cohorts. The first cohort required patients to have at least four pathologic axillary lymph nodes (or pALN) or 1-3 pALN plus a grade 3 tumor, or a tumor size of at least 50 millimeters. The second required that patients not be eligible for cohort 1, must have 1-3 pALN and a Ki-67 score of at least 20%.
From there, patients were randomized to either two years of Verzenio plus physician’s choice of endocrine therapy, or endocrine therapy alone.
FDA wrote that a statistically significant difference was seen in the intent-to-treat population, primarily because of the patients in cohort 1, which comprised 91% of the study population. The agency also noted that the indication is restricted to cohort 1 — as cohort 2 saw more deaths in patients on both Verzenio and standard endocrine therapy compared to endocrine therapy alone (10/253 vs. 5/264).
Lilly said in a statement that the expansion was backed by four-year data from the monarchE trial, which showed a 6.9% difference between the trial’s treatment groups in invasive disease-free survival, the trial’s primary endpoint.
“At four years, 85.5% of patients remained recurrence-free with Verzenio plus ET, compared to 78.6% with ET alone,” Lilly said, noting that the absolute differences between the treatment groups at two and three years were 3.1% and 5.0%, respectively.
Oncologist and monarchE investigator Erika Hamilton praised the decision, saying in a statement that “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.”
Originally, the Indiana drug giant ran a subgroup analysis in the monarchE trial on patients utilizing the diagnostic, showing that the combo of Verzenio and endocrine therapy displayed a 37% reduction of recurrence events in patients with a Ki-67 score of at least 20. However, a panel of breast cancer experts in late 2020 had previously slammed the test as having a “lack of analytical validity” due to potential outside factors that can impact the result. Those experts later said that Ki-67 should be reserved only in the case of very low scores (less than or equal to five) or very high scores (at least 30) in specific instances.
