Eli Lilly Announces FDA Approval Expansion for Abemaciclib in High-Risk Early Breast Cancer

On March 3, Eli Lilly and Company announced that the FDA has approved abemaciclib in combination with endocrine therapy (ET) for an expanded indication, applicable as adjuvant treatment for adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), lymph node-positive, high-risk of recurrence early breast cancer. This expanded adjuvant treatment indication removes the Ki-67 scoring requirement for patients. Currently, abemaciclib remains the only CDK4/6 inhibitor approved for adjuvant treatment.

Now, regardless of the Ki-67 score, high-risk patients eligible for abemaciclib treatment can be determined solely based on lymph node status, tumor size, and tumor grade (4+ positive lymph nodes, or 3-5 positive lymph nodes and at least one of the following: tumor ≥5 cm or grade 3).

Breast cancer is the most commonly diagnosed cancer among women globally. It is estimated that 90% of breast cancer cases are diagnosed at an early stage. The most common subtype is HR+/HER2-, which accounts for approximately 70% of all breast cancer patients. Although the prognosis for HR+, HER2- early-stage breast cancer is generally good, high-risk patients are three times more likely to experience recurrence compared to low-risk patients, and most will progress to incurable metastatic disease.

Cyclin-dependent kinases (CDKs) are members of the serine/threonine protein kinase family and play a crucial role in cell cycle regulation. Overexpression of CDK4/6 is observed in various cancers, leading to uncontrolled cell division cycles. Abemaciclib inhibits tumor cell proliferation by blocking the transition of tumor cells from the G1 phase to the S phase, while also inducing tumor cell senescence and apoptosis (programmed cell death).

In 2021, abemaciclib in combination with ET was approved in the United States for the adjuvant treatment of HR+/HER2-, lymph node-positive, high-risk of recurrence, and Ki-67≥20% early breast cancer patients. Abemaciclib became the first CDK4/6 inhibitor approved for adjuvant treatment of breast cancer.

This approval is mainly based on the 4-year data from the Phase III monarchE study. After 2 years of adjuvant treatment with abemaciclib combined with ET, the invasive disease-free survival (IDFS) benefit for patients deepened. The absolute difference in IDFS between the abemaciclib plus ET group and the ET alone group increased over time.

At Year 2 and Year 3, the absolute differences between the treatment groups were 3.1% and 5.0%, respectively. At Year 4, 85.5% of patients receiving abemaciclib plus ET remained recurrence-free, compared to 78.6% in the ET alone group, with an absolute difference of 6.9% in IDFS. Compared to ET alone, treatment with abemaciclib plus ET reduced the risk of recurrence by 35% (HR=0.653, 95% CI: 0.567-0.753).

"This expanded approval allows us to bring abemaciclib to more women and men with HR+/HER2- high-risk early breast cancer," said Jacob Van Naarden, CEO of Eli Lilly and Company. "The approval of abemaciclib has changed the treatment paradigm, and the monarchE study supporting this approval highlights the significant role this differentiated CDK4/6 inhibitor plays in reducing the risk of recurrence in early breast cancer."

While expanding the indication for early breast cancer, the FDA also broadened the indication for abemaciclib in metastatic breast cancer, specifically for use in combination with an aromatase inhibitor as the initial endocrine therapy for treating HR+/HER2- advanced or metastatic breast cancer, extending the treated population to include all adult patients, including premenopausal and perimenopausal patients.

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