Verzenio

HR+/HER2− Advanced or Metastatic Breast Cancer: In combination with an aromatase inhibitor as initial endocrine-based therapy in postmenopausal women and men.
HR+/HER2− Advanced or Metastatic Breast Cancer: In combination with fulvestrant in patients with disease progression following endocrine therapy.
HR+/HER2− Early Breast Cancer (adjuvant): In combination with endocrine therapy (tamoxifen or aromatase inhibitor) in adult patients with high risk of recurrence and Ki-67 score ≥20% (for node-positive disease).

Advanced/metastatic (with AI): 150 mg orally twice daily continuously
Advanced/metastatic (with fulvestrant): 150 mg orally twice daily continuously
Adjuvant early breast cancer: 150 mg orally twice daily continuously for up to 2 years
Administration: With or without food. Swallow tablets whole.
Dose reductions: First: 100 mg twice daily; Second: 50 mg twice daily. Discontinue if unable to tolerate 50 mg twice daily.

Tablets (film-coated): 50 mg, 100 mg, 150 mg, 200 mg

None listed in the prescribing information.

• Diarrhea: Most frequently reported adverse reaction. Instruct patients to start antidiarrheal therapy at first sign. Dose interruption and/or reduction may be required.
• Neutropenia: Monitor CBCs prior to initiation, every 2 weeks for first 2 months, monthly for next 2 months, and as clinically indicated.
• ILD/Pneumonitis: Fatal cases reported. Monitor for respiratory symptoms. Permanently discontinue for Grade 3/4.
• Hepatotoxicity: Monitor LFTs before initiation, every 2 weeks for first 2 months, monthly for next 2 months, and as clinically indicated.
• Venous Thromboembolism: DVT and PE reported. Monitor for signs/symptoms.
• Embryo-Fetal Toxicity: Can cause fetal harm. Verify pregnancy status before initiating.

Diarrhea (81%), Neutropenia (41%), Fatigue (40%), Infections (39%), Nausea (39%), Abdominal Pain (29%), Anemia (28%), Vomiting (26%), Decreased Appetite (24%), Headache (20%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Strong CYP3A Inhibitors: Avoid concurrent use. If unavoidable, reduce Verzenio dose to 100 mg twice daily (from 150 mg) or 50 mg twice daily (from 100 mg).
Strong CYP3A Inducers: Avoid concurrent use. If unavoidable, increase Verzenio dose up to 200 mg twice daily.
CYP3A Substrates: Abemaciclib is a CYP3A inhibitor at clinically relevant concentrations. The dose of sensitive CYP3A substrates with narrow therapeutic index may need reduction.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Abemaciclib is a selective inhibitor of CDK4 and CDK6 that are activated upon binding to D-cyclins. In ER+ breast cancer cell lines, abemaciclib (in combination with anti-estrogens) blocks Rb phosphorylation, preventing G1/S transition and inhibiting cell growth. Abemaciclib shows greater selectivity for CDK4/cyclin D1 over CDK6/cyclin D3 and is dosed continuously (unlike palbociclib/ribociclib) due to a distinct pharmacological profile that also allows penetration into the CNS.

Tmax: 8 hours. Bioavailability: 45%. Vd: 690 L. Protein binding: 96%. Metabolized by CYP3A4 to active metabolites M2 (~25% parent exposure), M20 (~26%), M18 (~8%). Half-life: 18 hours. Steady state by Day 5. Elimination: feces 81%, urine 3%.

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• MONARCH 3 — Abemaciclib + NSAI vs. placebo + NSAI as first-line in HR+/HER2− advanced breast cancer. Phase III, n=493.
  🔬 NCT02246621 ↗ 📄 Primary Publication ↗
• MONARCH 2 — Abemaciclib + fulvestrant vs. placebo + fulvestrant in HR+/HER2− advanced breast cancer after endocrine therapy. Phase III, n=669.
  🔬 NCT02107703 ↗ 📄 Primary Publication ↗
• monarchE — Adjuvant abemaciclib + ET vs. ET alone in HR+/HER2− high-risk early breast cancer. Phase III, n=5637.
  🔬 NCT03155997 ↗ 📄 Primary Publication ↗

Verzenio has FDA-approved indications across the following cancer types covered on PipelineEvidence: