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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Related Studies

Ontology: trastuzumab (C0728747)

Definition (NCI) A recombinant humanized monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2). After binding to HER2 on the tumor cell surface, trastuzumab induces an antibody-dependent cell-mediated cytotoxicity against tumor cells that overexpress HER2. HER2 is overexpressed by many adenocarcinomas, particularly breast adenocarcinomas. (NCI04)
Definition (NCI_NCI-GLOSS) A monoclonal antibody that binds to HER2 (human epidermal growth factor receptor 2), and can kill HER2-positive cancer cells. Monoclonal antibodies are made in the laboratory and can locate and bind to substances in the body, including cancer cells. Trastuzumab is used to treat breast cancer that is HER2-positive and has spread after treatment with other drugs. It is also used with other anticancer drugs to treat HER2-positive breast cancer after surgery. Trastuzumab is also being studied in the treatment of other types of cancer.
Definition (PDQ) A recombinant humanized monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2). After binding to HER2 on the tumor cell surface, trastuzumab induces an antibody-dependent cell-mediated cytotoxicity against tumor cells that overexpress HER2. HER2 is overexpressed by many adenocarcinomas, particularly breast adenocarcinomas. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42265&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42265&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1647" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Immunologic Factor (T129) , Amino Acid, Peptide, or Protein (T116)
MSH C112748
SnomedCT 116080004, 327397006, 387003001
English Anti-erbB2 Monoclonal Antibody, Anti-c-erbB2 Monoclonal Antibody, Anti-ERB-2, HER2 monoclonal antibody, anti-c-erB-2, Anti-HER2/c-erbB2 Monoclonal Antibody, Anti-p185-HER2, trastuzumab (medication), trastuzumab [Chemical/Ingredient], TRASTUZUMAB, Herceptin Trastuzumab Biosimilar PF-05280014, PF-05280014, Herceptin Biosimilar PF-05280014, Trastuzumab Biosimilar PF-05280014, ABP 980, Trastuzumab Biosimilar ABP 980, Trastuzumab, Trastuzumab (product), Trastuzumab (substance), monoclonal antibody HER2, monoclonal antibody c-erb-2, MOAB HER2, rhuMAb HER2, MoAb HER2, Monoclonal Antibody HER2, Monoclonal Antibody c-erb-2, Anti-c-ERB-2, c-erb-2 Monoclonal Antibody, HER2 Monoclonal Antibody, Anti-erbB-2, trastuzumab
Spanish trastuzumab (concepto no activo), trastuzumab (producto), trastuzumab (sustancia), trastuzumab