Abemaciclib After Breast Cancer Surgery Shows Sustained Long-Term Efficacy

The benefit of adding abemaciclib to hormonal therapy for 2 years after breast cancer surgery was demonstrated in the large monarchE study's 5-year long-term findings , presented at the ESMO 2023 Congress.

Abemaciclib (brand name Yulareb, manufactured by Eli Lilly Company) was approved by the FDA (US Food and Drug Administration) on October 12, 2021, for adjuvant treatment (protective treatment after surgery) of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor (HER2)-negative, node-positive early breast cancer at high risk of recurrence.

Patients with early-stage hormone-positive breast cancer who are at high risk of recurrence are defined as follows:

• Patients with 4 or more pathologically positive axillary lymph nodes; or
• Patients with 1-3 pathologically positive axillary lymph nodes and a tumor grade of 3; or
• Patients with a tumor size of 50 mm or greater.

In this patient group, abemaciclib reduces the risk of cancer recurrence when used in addition to endocrine therapy (tamoxifen or an aromatase inhibitor).

5-Year Results

These data came from the third interim analysis of monarchE, with a median follow-up of 54 months at the data cutoff on July 3, 2023.

At this 5-year milestone, all patients had stopped taking abemaciclib, and notably, more than 80% of patients had been followed for at least 2 years.

At the end of the fifth year, the benefit of adding abemaciclib to endocrine therapy (ET) on IDFS persisted across the entire patient population. There were 407 invasive disease events in the abemaciclib group, compared with 585 in the ET-only group. This represents a 32% reduction in the risk of invasive disease with abemaciclib (hazard ratio [HR], 0.680; 95% confidence interval [CI], 0.599-0.772). At five years, IDFS was 83.6% in patients receiving abemaciclib and 76.0% in those receiving ET alone.

The IDFS benefit of abemaciclib was consistent across various subgroups. These results did not vary with patients' age, menopausal status, type of chemotherapy received (neoadjuvant or adjuvant), number of positive lymph nodes, or type of endocrine therapy combined with abemaciclib (tamoxifen or an aromatase inhibitor).

Similarly, across the entire patient population, adding abemaciclib to ET continued to have a beneficial effect on DRFS (distant relapse-free survival) . Patients treated with the addition of abemaciclib experienced fewer distant recurrences than those treated with ET alone: 345 events in the abemaciclib group versus 501 in the ET-only group. This shows that adding abemaciclib reduced the risk of distant recurrence by 32.5% (hazard ratio [HR], 0.675; 95% confidence interval [CI], 0.588-0.774). At five years, DRFS was 86.0% in patients receiving abemaciclib and 79.2% in those receiving ET alone.

Overall survival results are not yet fully mature, but fewer deaths were reported in the abemaciclib arm than in the control arm. There were 208 deaths in the abemaciclib group and 234 in the placebo group. These data yielded a hazard ratio (HR) of 0.903, a 95% confidence interval (CI) of 0.749-1.088, and a p-value of 0.284.

Adverse Effects

The 5-year results identified no new safety signals, and the adverse effect findings were reported to be similar to those of earlier analyses.

The most common adverse effects associated with abemaciclib were diarrhea, neutropenia, and fatigue; the most common grade 3 to 4 adverse effects were neutropenia, leukopenia, and diarrhea.

At least one TEAE was observed in 98.4% of patients treated with abemaciclib, compared with 88.9% of patients receiving ET alone. This indicates that patients treated with abemaciclib experienced treatment-related adverse events more frequently.

At least one grade 3 or higher TEAE was reported in 50.0% of patients treated with abemaciclib, compared with 16.9% of those receiving ET alone. This indicates that patients treated with abemaciclib experienced severe adverse effects more frequently.

However, during the 5-year long-term follow-up, serious AEs were reported in 6.5% of patients treated with abemaciclib plus ET and 7.3% of those receiving ET alone. This indicates that serious adverse effects were less frequent over the long term in patients receiving abemaciclib than in those receiving ET alone.

The NATALEE Study (Ribociclib)

Ribociclib has not yet received FDA approval for treating these patients. Its efficacy as adjuvant treatment in patients with early-stage hormone-positive breast cancer was evaluated in the NATALEE study, whose 3-year results were presented at the ESMO 2023 Congress.

The NATALEE study enrolled  

• 4297 patients with stage 2 and 3 hormone receptor-positive, HER2-negative breast cancer.
• In the experimental arm, patients received an aromatase inhibitor (letrozole or anastrozole) for 60 months with ribociclib for 3 years, while the control arm received an aromatase inhibitor alone.
• Findings:
  • 3-year invasive disease-free survival was 90.7% with ribociclib versus 87.6% in the control arm.
  • 3-year recurrence-free survival was 92.1% with ribociclib versus 89.1% in the control arm.
  • 3-year overall survival was 97% with ribociclib versus 96.1%; however, this difference was not statistically significant.
• Adverse Effects: Grade 3 or higher neutropenia occurred in 44.3% of patients in the ribociclib arm.

Comparing NATALEE and monarchE

• Patient Characteristics: Both studies examine patients with hormone receptor-positive, HER2-negative breast cancer, but monarchE focuses on higher-risk patients.
• Treatment Duration: Abemaciclib is given for 2 years in monarchE, while ribociclib is given for 3 years in NATALEE.
• Efficacy: In both studies, CDK 4/6 inhibitors improved invasive disease-free survival (IDFS). In monarchE, abemaciclib produced greater improvements in the measured survival rates (7.6% improvement in IDFS and 6.7% in DRFS).
• Adverse Effects: Both drugs cause adverse effects, but a broader adverse effect profile is seen with abemaciclib in monarchE.