Ado-trastuzumab emtansine (T-DM1): a novel antibody-drug conjugate for the treatment of HER2-positive metastatic breast cancer

J Oncol Pharm Pract. 2015 Apr;21(2):132-42. doi: 10.1177/1078155214527144. Epub 2014 Mar 27.

Abstract

Human epidermal growth factor receptor-2 (HER2)-positive breast cancer is an aggressive form of breast cancer associated with poorer prognosis and shortened survival. Primary and acquired resistance to existing HER2-targeted therapies presents a challenge for the management of patients with HER2-positive metastatic breast cancer. Ado-trastuzumab emtansine, a drug-antibody conjugate, has shown promising results for patients failing prior treatment with trastuzumab. Ado-trastuzumab emtansine consists of the monoclonal antibody trastuzumab linked to a potent microtubule inhibitor (emtansine), allowing a targeted delivery of chemotherapy to cells that overexpress HER2. Ado-trastuzumab emtansine has been approved for use in patients with metastatic breast cancer who have failed prior therapy with trastuzumab and a taxane. Although well-tolerated in clinical trials, thrombocytopenia has been reported and platelet values should be monitored closely. Increased liver enzymes and bilirubin, as well as cardiotoxicity, have also been documented, and recommendations for dose reduction or discontinuation due to these toxicities are available. Clinical trials are currently ongoing to further define the role of ado-trastuzumab emtansine in both the metastatic and early breast cancer settings.

Keywords: Ado-trastuzumab emtansine; T-DM1; human epidermal growth factor receptor-2-positive; metastatic breast cancer.

Publication types

  • Review

MeSH terms

  • Ado-Trastuzumab Emtansine
  • Animals
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology
  • Female
  • Humans
  • Immunoconjugates / adverse effects
  • Immunoconjugates / therapeutic use*
  • Maytansine / adverse effects
  • Maytansine / analogs & derivatives*
  • Maytansine / therapeutic use
  • Neoplasm Metastasis
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / metabolism
  • Signal Transduction / drug effects
  • Trastuzumab
  • Treatment Outcome
  • Tubulin Modulators / adverse effects
  • Tubulin Modulators / therapeutic use*

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Immunoconjugates
  • Tubulin Modulators
  • Maytansine
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab
  • Ado-Trastuzumab Emtansine