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

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.