Trastuzumab

Information about Trastuzumab

Trastuzumab is a humanized monoclonal antibody to the HER2 receptor which is used in combination with other antineoplastic agents in the therapy of breast and gastric cancer.   

Trastuzumab-HER2 complex

Liver safety of Trastuzumab

Trastuzumab has been implicated in rare instances of transient, marked serum enzyme elevations, but has not been linked to instances of clinically apparent liver injury with jaundice.  In contrast, the recently developed conjugate of trastuzumab with the microtubule inhibitor emtansine, which is used as an antineoplastic agent for advanced resistant breast cancer, has been linked to frequent serum enzyme elevations during therapy and, when given chronically, to nodular regenerative hyperplasia. 

Mechanism of action of Trastuzumab

Trastuzumab (tras tooz’ ue mab) is humanized monoclonal antibody to HER2 which is a human growth factor receptor that is overexpressed in 20% to 25% of breast cancers.  The interaction of epidermal growth factor (EGF) with HER2 results in rapid cell growth and proliferation via intracellular pathways that include MAP and PI3 kinase.  Binding of trastuzumab to the HER2 receptor blocks this cell signaling pathway and causes growth arrest.  Trastuzumab was shown to decrease recurrences and prolong survival in women with breast cancer that were HER2 positive. 

FDA approval information for Trastuzumab

Trastuzumab was approved for use in the United States in 1998 and current indications include breast and gastric cancers that express HER2.  Trastuzumab is available in multiple use vials under the brand name Herceptin.  The typical dose is 2 to 8 mg/kg intravenously every week, the dose and duration of therapy varying with different indications. 

{se}} Common side effects include fatigue, nausea and vomiting, diarrhea, infusion reactions, rash, headache, neutropenia, infections and anemia.  Rare, but serious side effects include infusion reactions (usually with the initial dose), cardiomyopathy (especially when combined with an anthracycline), pneumonitis and fetal toxicity.

Ado-trastuzumab emtansine (em tan’ seen) is a conjugate of trastuzumab with emtansine (DM1), a microtubule inhibitor derived from maytansine that is taken up with trastuzumab into HER2 expressing cancer cells and degraded in lysosomes resulting in release of DM1, which binds to tubulin and disrupts microtubular networks resulting in cell cycle arrest and cell death.  This conjugate, when combined with other antineoplastic agents, has shown increased efficacy in advanced, metastatic breast cancer.  Ado-trastuzumab emtansine was approved for use in previously treated, advanced breast cancer in the United States in 2013, and experience with its use has been limited.  The antibody conjugate is available in single use vials under the brand name Kadcyla.  The recommended dose is 3.6 mg/kg intravenously every 3 weeks until disease progression or intolerability.  The antibody conjugate has a higher rate of adverse side effects than trastuzumab alone; the more common adverse events include fatigue, nausea, myalgias, headache, constipation, serum enzyme elevations and thrombocytopenia. 

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• Dailymed label info on Trastuzumab
• FDA Trastuzumab

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