What is the recommended use and dosage of Verzenio (abemaciclib) for breast cancer treatment?

Verzenio (Abemaciclib) for Breast Cancer Treatment

For breast cancer treatment, Verzenio (abemaciclib) is recommended at a dose of 150 mg orally twice daily when used in combination with endocrine therapy (aromatase inhibitor or fulvestrant) for HR-positive, HER2-negative breast cancer, or 200 mg twice daily when used as monotherapy. 1

Indications for Verzenio

Early Breast Cancer

• Adjuvant treatment: In combination with endocrine therapy (tamoxifen or aromatase inhibitor) for HR-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence 1
  • Continue for 2 years or until disease recurrence/unacceptable toxicity
  • Category 1, preferred option for high-risk patients 2
  • Demonstrated significant reduction in recurrence risk (HR 0.664) in the MonarchE study 2

Advanced or Metastatic Breast Cancer

• First-line therapy: In combination with an aromatase inhibitor for HR-positive, HER2-negative advanced/metastatic breast cancer 1

  • MONARCH 3 trial showed improved PFS (28.18 vs 14.76 months) 2

• Second-line therapy: In combination with fulvestrant for HR-positive, HER2-negative advanced/metastatic breast cancer with disease progression following endocrine therapy 1

  • MONARCH 2 trial showed improved PFS (16.4 vs 9.3 months) and OS (46.7 vs 37.3 months) 2

• Later-line monotherapy: For HR-positive, HER2-negative advanced/metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy 1

  • MONARCH 1 trial showed 19.7% objective response rate and median PFS of 6 months 2

Dosing and Administration

Dosing Schedule

• Combination therapy: 150 mg orally twice daily 1
• Monotherapy: 200 mg orally twice daily 1
• Take with or without food at approximately the same times each day 1
• Swallow tablets whole; do not chew, crush, or split 1

Special Populations

• Pre/perimenopausal women: Must receive ovarian suppression/ablation with GnRH agonist when using with aromatase inhibitors 1
• Men: Should be treated with GnRH agonist when using with aromatase inhibitors 1

Monitoring and Management of Side Effects

Required Monitoring

• Complete blood counts: Prior to starting therapy, every 2 weeks for first 2 months, monthly for next 2 months, then as clinically indicated 1
• Liver function tests: Same schedule as CBC 1

Common Adverse Effects and Management

1. Diarrhea (most common, 81.3% of patients) 2

   • Start antidiarrheal agents at first sign of loose stools
   • Increase fluid intake
   • Grade 2 persisting >24 hours: Suspend dose until resolution to ≤Grade 1
   • Grade 3-4: Suspend dose and resume at lower dose when resolved to ≤Grade 1

2. Neutropenia (21-27% Grade 3-4) 2

   • Grade 3: Suspend dose until resolves to ≤Grade 2; no dose reduction required
   • Grade 3 recurrent or Grade 4: Suspend dose and resume at lower dose when resolved to ≤Grade 2

3. Hepatotoxicity

   • For persistent Grade 2, or Grade 3: Suspend dose until resolves to baseline or Grade 1
   • For Grade 4 or elevated bilirubin: Discontinue Verzenio

Dose Modifications

Dose Reduction Levels

• Combination therapy:

  • Starting: 150 mg twice daily
  • First reduction: 100 mg twice daily
  • Second reduction: 50 mg twice daily

• Monotherapy:

  • Starting: 200 mg twice daily
  • First reduction: 150 mg twice daily
  • Second reduction: 100 mg twice daily
  • Third reduction: 50 mg twice daily

• Discontinue if unable to tolerate 50 mg twice daily 1

Clinical Considerations

Efficacy Comparisons

• Abemaciclib is the only CDK4/6 inhibitor approved for adjuvant treatment of early breast cancer at high risk of recurrence 2, 3
• In metastatic setting, all three CDK4/6 inhibitors (abemaciclib, palbociclib, ribociclib) have shown significant improvements in PFS 2
• Abemaciclib has unique approval as monotherapy after progression on endocrine therapy and chemotherapy 1

Treatment Duration

• Early breast cancer: Continue for 2 years or until disease recurrence/toxicity 1
• Advanced/metastatic disease: Continue until disease progression or unacceptable toxicity 1

Common Pitfalls to Avoid

1. Inadequate diarrhea management: Proactive antidiarrheal treatment is essential
2. Insufficient monitoring: Regular CBC and LFT monitoring is crucial, especially in first 4 months
3. Overlooking drug interactions: Consider potential interactions with CYP3A4 inhibitors/inducers
4. Not using ovarian suppression: Pre/perimenopausal women must receive ovarian suppression with aromatase inhibitors
5. Continuing after progression: No data support using another CDK4/6 inhibitor-containing regimen after progression on abemaciclib 4

By following these evidence-based recommendations for Verzenio (abemaciclib), clinicians can optimize treatment outcomes while effectively managing side effects for patients with HR-positive, HER2-negative breast cancer.