Cyclin-Dependent Kinase Inhibitor

Aka: Cyclin-Dependent Kinase Inhibitor, CDK Inhibitor, Palbociclib, Ibrance, Ribociclib, Kisquali, Abemaciclib, Verzenio

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II. Indications

  1. Hormone Receptor positive, HER2 Negative advanced or metastatic Breast Cancer

III. Contraindications

  1. QT Prolongation (Ribociclib)
    1. Also correct Electrolyte abnormalities (e.g. Magnesium, Potassium) before use
    2. Avoid with other Medication Causes of QTc Prolongation

IV. Mechanism

  1. Cyclin-Dependent Kinase
    1. CDK4 (Cyclin D1) and CDK6 (Cyclin D3) are Serine-Threonine kinases
    2. These kinases become unregulated in some tumor types (e.g. Retinoblastoma), resulting in tumor cell growth
  2. Cyclin-Dependent Kinase 4 and 6 Inhibitor (CDK 4 and 6)
    1. Selective inhibition of Cyclin-Dependent Kinase CDK4 and CDK6
    2. Inhibit Retinoblastoma (Rb) Protein phosphorylation during early G1-S Phase and results in Cell Cycle arrest

V. Medications

  1. Palbociclib (Ibrance)
    1. Risks include Neutropenia, Venous Thromboembolism
    2. Avoid with strong CYP3A Inhibitors, strong CYP3A Inducers and narrow therapeutic range CYP3A Substrates
  2. Ribociclib (Kisquali)
    1. Risks include Neutropenia, QT Prolongation, hepatotoxicity
    2. Avoid with strong CYP3A Inhibitors, strong CYP3A Inducers and narrow therapeutic range CYP3A Substrates
  3. Abemaciclib (Verzenio)
    1. Risk of severe Diarrhea, Neutropenia, hepatotoxicity, Venous Thromboembolism
    2. Avoid with strong CYP3A Inhibitors and strong CYP3A Inducers

VI. Dosing

  1. See other references for disease specific dosing protocols

VII. Adverse Effects

  1. Neutropenia (all CDK Inhibitors)
  2. Venous Thromboembolism (Palbociclib, Abemaciclib)
  3. Hepatotoxicity (Ribociclib, Abemaciclib)
  4. QT Prolongation (Ribociclib)
  5. Severe Diarrhea (Abemaciclib)

VIII. Safety

  1. Avoid in Lactation
  2. Avoid in pregnancy (all trimesters, pregnancy category X)
    1. Use reliable Contraception including for at least 2 weeks after last dose
    2. Men should use reliable Contraception for at least 3 months after last dose of Palbociclib
  3. Monitoring
    1. Complete Blood Count
      1. Obtain baseline, and per cycle regimen
    2. Electrocardiogram (Ribociclib)
    3. Liver Function Tests (Ribociclib, Abemaciclib)

IX. Drug Interactions

  1. Strong CYP3A Inhibitors, strong CYP3A Inducers and narrow therapeutic range CYP3A Substrates
    1. Avoid with Palbociclib, Ribociclib, Abemaciclib
  2. Medication Causes of QTc Prolongation
    1. Avoid with Ribociclib

X. Resources

  1. Palbociclib (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e0e6412f-50b4-4fd4-9364-62818d121a07
  2. Ribociclib (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aaeaef94-f3f5-4367-8ea2-b181d7be2da8
  3. Abemaciclib (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=be4bc0de-0fdc-4d46-8d25-be43c79e6a06

XI. References

  1. Ettl (2022) Cancers 14(2):293 +PMID: 35053461 [PubMed]

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