II. Indications

  1. Breast Cancer (HER2 Positive)
    1. Trastuzumab
    2. Ado-Trastuzumab Emtansine
    3. Pertuzamab
  2. Gastric Cancer (metastatic, HER2 Positive)
    1. Trastuzumab

III. Mechanism

  1. Human Epidermal Growth Factor Receptor 2 (HER2, HER2/neu, erbB-2 Receptor, CD340 Antigen)
    1. HER2/neu is a EGFR related Tyrosine Kinase important in Breast Cancer
    2. HER2 is overexpressed by many adenocarcinomas (esp. Breast adenocarcinoma)
    3. Overexpression of HER2/neu may predict worse prognosis and cancer recurrence
  2. Epidermal Growth Factor Receptor (EGFR, HER1, ErbB1)
    1. EGFR is a Tyrosine Kinase that is activated by specific Ligands
    2. Triggers cascade that leads to cell proliferation, invasion and migration
  3. Anti-HER2 Monoclonal Antibody
    1. Recombinant human Monoclonal Antibody directed against the HER2 cell surface receptor
    2. Binds HER2 and triggers a cell-mediated cytotoxic immune response
      1. Targeted most significantly against tumor cells overexpressing HER2

IV. Medications: Anti-HER2

  1. Trastuzumab (Herceptin)
    1. Used in Breast Cancer (where HER2-neu is overexpressed) and metastatic HER2+ Gastric Cancer
    2. Trastuzumab has been very effective in HER2 positive Breast Cancer
    3. Risk of infusion reactions, pneumonitis, Cardiomyopathy, cytopenias
    4. Trastuzumab Biosimilar agents
      1. Trastuzumab-ANNS (Kanjinti)
      2. Trastuzumab-DTTB (Ontruzant)
      3. Trastuzumab-PKRB (Herzuma)
      4. Trastuzumab-QYYP (Trazimera)
  2. Pertuzamab (Perjeta)
    1. Risk of infusion reactions, Cardiomyopathy, cytopenias

V. Medications: Anti-HER2 with Cytotoxic Conjugates

  1. Ado-Trastuzumab Emtansine (Kadcyla)
    1. Trastuzumab is conjugated to the cytotoxic agent emtansine (DM1), a microtubule inhibitor
    2. Delivers cytotoxic DM1 to HER2 positive cells (e.g. Breast Cancer)
    3. Risk of Trastuzumab adverse effects, as well as hepatotoxicity, bleeding

VI. Dosing

  1. See other references for disease specific dosing protocols

VII. Adverse Effects

  1. Infusion Reaction (Trastuzumab, Pertuzamab)
    1. Anaphylaxis
    2. Angioedema
  2. Cardiomyopathy (box warning, Trastuzumab, Pertuzamab)
    1. Congestive Heart Failure
  3. Lung Toxicity (box warning, Trastuzumab)
    1. Interstitial pneumonitis
    2. Acute Respiratory Distress Syndrome
  4. Cytopenia (Trastuzumab)
    1. Neutropenia
    2. Anemia
    3. Thrombocytopenia
  5. Hepatotoxicity (Ado-Trastuzumab Emtansine)
  6. Major Bleeding (Ado-Trastuzumab Emtansine)
  7. Other common adverse effects
    1. Diarrhea
    2. Stomatitis
    3. Headache

VIII. Safety

  1. Avoid in Lactation
  2. Avoid in pregnancy (all trimesters, Pregnancy category X)
    1. Risk of pulmonary hypoplasia, oligohydramnios, neonatal death
    2. Use reliable Contraception
  3. Monitoring
    1. Complete Blood Count
    2. Electrocardiogram
    3. Echocardiogram

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