Current Clinical Use of Abemaciclib in Breast Cancer
Abemaciclib is now used in two distinct settings for HR+/HER2- breast cancer: as adjuvant therapy for high-risk early breast cancer and as treatment for advanced/metastatic disease in combination with endocrine therapy. 1, 2
Adjuvant Setting: High-Risk Early Breast Cancer
The NCCN and ASCO recommend abemaciclib 150 mg twice daily for 2 years combined with endocrine therapy (minimum 5 years) as a Category 1 preferred option for patients with high-risk, HR+/HER2- early breast cancer. 1, 2
Patient Selection Criteria for Adjuvant Use
High-risk is specifically defined as patients meeting one of the following criteria: 1
- ≥4 positive lymph nodes, OR
- 1-3 positive lymph nodes PLUS at least one of:
- Tumor ≥5 cm
- Histologic grade 3
- Ki-67 ≥20%
Efficacy in the Adjuvant Setting
The benefit is substantial and sustained: 1
- 7.6% absolute improvement in invasive disease-free survival (IDFS) at 5 years
- 6.7% absolute improvement in distant recurrence-free survival (DRFS) at 5 years
- Hazard ratio of 0.680 (95% CI, 0.599-0.772) for IDFS with median follow-up of 54 months
Advanced/Metastatic Disease Setting
First-Line Therapy
Abemaciclib combined with an aromatase inhibitor is a Category 1 preferred option for postmenopausal women (or premenopausal women receiving ovarian suppression) with HR+/HER2- recurrent or stage IV breast cancer. 2
- Median PFS not reached versus 14.7 months with aromatase inhibitor alone (HR 0.54; 95% CI 0.41-0.72) 2
After Progression on Prior Endocrine Therapy
Abemaciclib plus fulvestrant is a Category 1 preferred option for patients who have progressed on prior endocrine therapy, demonstrating improved PFS, objective response rate, and overall survival. 2
Dosing Regimen
The standard dosing differs by setting: 2
- Adjuvant setting: 150 mg orally twice daily continuously for 2 years
- Metastatic setting: 150 mg orally twice daily continuously until progression or unacceptable toxicity
Safety Profile and Management Considerations
Common Adverse Events
Grade ≥3 adverse events occur in 50% of patients receiving abemaciclib plus endocrine therapy versus 16% with endocrine therapy alone. 1 The most frequent adverse events include: 1, 2
- Diarrhea: 81-90% (grade 3 in 9.5%)
- Neutropenia: 21-45% (grade 3/4 in 21-27%)
- Fatigue: 40-65%
- Nausea: 64%
Serious Safety Concerns
Critical adverse events to monitor: 1
- Thromboembolic events: 3% of patients
- Interstitial lung disease: 3% of patients
- Fatal adverse events: 0.8% of patients
Key Clinical Pitfall
Abemaciclib requires continuous daily dosing without treatment breaks, distinguishing it from some other CDK4/6 inhibitors. 2 This continuous schedule is essential for maintaining efficacy based on its mechanism of action. 3