ALK Inhibitor


ALK Inhibitor, ALK Tyrosine Kinase, Anaplastic Lymphoma Kinase Inhibitor, CD246, Alectinib, Alecensa, Brigatinib, Alunbrig, Ceritinib, Zykadia, Crizotinib, Xalkori, Lorlatinib, Lorbrena

  • Indications
  1. Non-Small Cell Lung Cancer (ALK+ fusion, metastatic)
  • Mechanism
  1. Anaplastic Lymphoma Kinase (ALK Tyrosine Kinase)
    1. ALK Receptors are Insulin receptors key to Central Nervous System development
      1. Also found in the developing Small Intestine and Testes
    2. ALK receptors are not normally expressed in adults
    3. ALK receptors are expressed in certain cancers, associated with gene dysregulation
      1. Non-Small Cell Lung Cancer
      2. Anaplastic large cell Lymphoma
  2. ALK Receptor Antagonists are small molecule, Tyrosine Kinase Inhibitors specific to ALK receptors
    1. Agents that block ALK, suppress specific tumor cell growth
  • Medications
  1. Alectinib (Alecensa)
    1. Multi-kinase Inhibitor
    2. Adverse effects include hepatotoxicity, Interstitial Lung Disease (ILD), Bradycardia, CPK Increase
    3. No major Drug Interactions
  2. Brigatinib (Alunbrig)
    1. Adverse effects include ILD, Bradycardia, Hypertension, Vision change, CPK increase, Pancreatitis, Hyperglycemia
    2. Drug Interactions include strong CYP3A4 inhibitors and inducers (also may render OCPs ineffective)
  3. Ceritinib (Zykadia)
    1. Multi-kinase Inhibitor
    2. Adverse Effects include hepatotoxicity, Pancreatitis, ILD, Bradycardia, QT Prolongation, Hyperglycemia
    3. Increased absorption with fatty meal (and decreased with Proton Pump Inhibitors)
  4. Crizotinib (Xalkori)
    1. Also blocks c-Met/hepatocyte growth factor receptor (HGFR); aso blocks ROS1 (see ROS1 Inhibitor)
    2. Adverse Effects include ILD, hepatotoxicity, Bradycardia, QT Prolongation
  5. Lorlatinib (Lorbrena)
    1. Adverse Effects include hepatotoxicity, ILD, CNS effects, Hyperlipidemia, AV Block
    2. Drug Interactions include strong CYP3A4 inhibitors and inducers (also may render OCPs ineffective)
  • Adverse Effects
  1. Cardiovascular
    1. Bradycardia (all agents)
    2. QTc Prolongation (Ceritinib, Crizotinib)
    3. Hypertension (Brigatinib)
    4. AV Block (Lorlatinib)
  2. Hepatotoxicity
    1. Primarily occurs with Alectinib, Ceritinib, Crizotinib, Lorlatinib
    2. Monitor Liver Function Tests every 2 weeks during the first 3 months of therapy (esp. Alectinib)
  3. Interstitial Lung Disease (ILD) or Pneumonitis
    1. Occurs with all agents: Brigatinib (9%), Alectinib (0.4%), Ceritinib, Crizotinib, Lorlatinib
  4. Creatine Phosphokinase (CPK) Increased or severe myalgias
    1. Occurs with Alectinib (up to 4%) and Brigatinib
  5. Lipase Elevation or Pancreatitis
    1. Occurs with Brigatinib and Ceritinib
  6. Hyperglycemia
    1. Occurs with Brigatinib, Ceritinib
  7. Hyperlipidemia
    1. Occurs with Lorlatinib
  8. Ocular Toxicity or visual disturbance
    1. Occurs with Brigatinib
  9. CNS Toxicity (Seizures, altered cognitive function, Hallucinations, altered speech)
    1. Occurs with Lorlatinib
  10. Nausea or Vomiting
  • Safety
  1. Avoid in Lactation
  2. Avoid in pregnancy (all trimesters)
    1. Use reliable Contraception
    2. Use non-Hormonal Contraception with Brigatinib, Ceritinib, Lorlatinib (OCPs may fail)
  • Efficacy
  1. Alectinib is highly effective in advanced ALK Lung Cancer
  • Drug Interactions
  1. Strong CYP3A4 inhibitors and inducers
    1. Brigatinib, Ceritinib, Lorlatinib
  2. Proton Pump Inhibitors
    1. Ceritinib