Abemaciclib Receives FDA Approval for Early-Stage Breast Cancer Treatment

On October 12, 2021, the FDA (US Food and Drug Administration) approved the CDK 4/6 medicine abemaciclib (Yulareb, Verzenios Eli Lilly Company) with endocrine therapy (tamoxifen or an aromatase inhibitor) for adjuvant (postoperative preventive) treatment of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor (HER2)-negative, node-positive early-stage breast cancer at high risk of recurrence.

Patients at high risk of recurrence are defined as follows:

• a pathological axillary lymph node count ≥4, or
• a pathological axillary lymph node count of 1-3 and tumor grade 3, or
• patients with tumor size ≥50 mm.

What is Ki-67?

Ki-67 is a protein that increases in a cell as it prepares to divide. A special cell-staining procedure can measure the percentage of tumor cells positive for Ki-67. The more positive cells there are, the faster the cancer is dividing and forming new cells. In breast cancer, a result below 10% is considered low, 10-20% borderline, and above 20% high.

FDA Approval Based on the monarchE Study

Efficacy was assessed in monarchE, a randomized (1:1), open-label, two-group, multicenter study including adult women and men with resected, HR-positive, HER2-negative, node-positive early breast cancer and clinical and pathological features consistent with a high recurrence risk.

Patients were randomly assigned to one of two study groups to receive either 2 years of abemaciclib plus their physician's choice of standard endocrine therapy, or standard endocrine therapy alone.

The main efficacy outcome measure was invasive disease-free survival (invasive disease-free survival= IDFS), an indicator of cancer recurrence.

Results

The study enrolled 2003 patients with Ki-67 scores ≥20% and a high recurrence risk.

• Abemaciclib produced a significant improvement in disease-free survival (HR 0.626; 95% CI: 0.488, 0.803; p=0.0042). It reduced the likelihood of cancer recurrence by 37%.
• At 36 months, disease-free survival was 86.1% (95% CI: 82.8, 88.8) in patients receiving abemaciclib plus tamoxifen or an aromatase inhibitor, and 79% (95% CI: 75.3, 82.3) in those receiving hormonal therapy alone (tamoxifen or an aromatase inhibitor).

Overall survival data were immature at the time of the disease-free survival analysis.

The most common (≥20%) adverse effects were diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia and headache.

The recommended starting abemaciclib dose is 150 mg twice daily with tamoxifen or an aromatase inhibitor until completion of 2 years of treatment, disease recurrence or unacceptable toxicity.