title: Trastuzumab emtansine in breast cancer.
abstract: BACKGROUND
  Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate (ADC) composed of trastuzumab, a stable linker (MCC), and the cytotoxic agent DM1 (derivative of maytansine). Administration of T-DM1 leads to limited systemic exposure of free DM1, with no evidence of DM1 accumulation after repeated dosing.
  
  
  METHODS
  Phase I and Phase II clinical trials with T-DM1 as a single agent and in combination with paclitaxel, docetaxel, and pertuzumab have shown substantial clinical activity and a favorable safety profile. A randomized, open-label, first-line trial comparing trastuzumab and docetaxel with single agent T-DM1 showed a significant improved progression-free survival for T-DM1.
  
  
  CONCLUSIONS
  T-DM1 has successfully completed second-line Phase III development for advanced HER2-positive breast cancer. The Phase III EMILIA study demonstrated an overall survival benefit for T-DM1 compared to the combination of lapatinib and capecitabine in taxane-trastuzumab pretreated patients. T-DM1 may offer delivery on a personalized basis of very potent cytotoxic agents in a cellular selective manner.
authors.affiliation: St Augustinus Hospital, Translational Cancer Research Group Antwerp, Oosterveldlaan 24, Wilrijk-Antwerp, 2610, Belgium.
authors.forename: Luc Y
authors.initials: LY
authors.lastname: Dirix
authors.forename: Annemie
authors.initials: A
authors.lastname: Rutten
authors.forename: Philippe
authors.initials: P
authors.lastname: Huget
authors.forename: Marie
authors.initials: M
authors.lastname: Dirix
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D000069287:Capecitabine; D002986:Clinical Trials as Topic / Q000379:methods; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage; D000077341:Lapatinib; D008453:Maytansine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D000069287:Capecitabine; D003841:Deoxycytidine; D000077143:Docetaxel; D005472:Fluorouracil; D018796:Immunoconjugates; D000077341:Lapatinib; D008453:Maytansine; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C080625:taxane; C508053:ERBB2 protein, human