title: Trastuzumab emtansine in advanced human epidermal growth factor receptor 2-positive breast cancer.
abstract: BACKGROUND
  Ado- trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate composed of trastuzumab, a stable linker (MCC), and the cytotoxic agent DM1 (derivative of maytansine; mertansine). T-DM1 retains the mechanisms of action of trastuzumab, but also acts as a, selectively delivered, tubulin inhibitor. Following antigen-mediated binding to the tumor cell, T-DM1 is endocytosed and intracellularly catabolized resulting in the release of its cytotoxic moiety.
  
  
  METHODS
  T-DM1 has completed Phase III development and compared favorably with the lapatinib/capecitabine combination with a superior response rate (objective response rate [ORR]) and duration of response, longer duration of disease control (progression-free survival [PFS]), prolonged overall survival and improved tolerability and quality of life in patients with prior treatment with trastuzumab and a taxane. In a separate Phase III, T-DM1 was compared with any other chosen regimen in patients who had at least received two prior HER2-directed therapies. T-DM1 nearly doubled PFS.
  
  
  CONCLUSIONS
  T-DM1 (Kadcyla) has become the treatment of choice in second-line and beyond for patients with advanced HER2-expressing breast cancer.
authors: Sint-Augustinus Cancer Center, Department of Medical Oncology , Sint-Augustinus, Oosterveldlaan 24, 2610 Wilrijk-Antwerp , Belgium +003234433737 ; luc.dirix@gza.be.
authors: Tom
authors: T
authors: Van den Mooter
authors: Laure-Anne
authors: LA
authors: Teuwen
authors: Annemie
authors: A
authors: Rutten
authors: Luc
authors: L
authors: Dirix
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D002986:Clinical Trials as Topic / Q000379:methods; D018572:Disease-Free Survival; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006801:Humans; D008453:Maytansine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D000068878:Trastuzumab
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008453:Maytansine; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: human epidermal growth factor receptor 2; metastatic breast cancer; pertuzumab; trastuzumab; trastuzumab emtansine