title: Trastuzumab emtansine (T-DM1) for HER2-positive breast cancer.
abstract: BACKGROUND
  Trastuzumab emtansine (T-DM1), a novel drug developed for the treatment of HER2-positive breast cancer, is a human epidermal growth factor receptor (HER2) targeted antibody drug conjugate, composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent DM1 (derivative of maytansine). It has been shown that, in preclinical studies, it has anti-tumor activity in trastuzumab refractory cancer cells. In this review, we aim to show the clinical data about trastuzumab-DM1 (T-DM1) therapy and to discuss the therapy advantages for the management of patients with HER2-positive breast cancer.
  
  
  METHODS
  T-DM1 showed positive results in clinical studies of HER2-positive metastatic breast cancer. PubMed database, ASCO and San Antonio Breast Cancer Symposium Meeting abstracts were searched up to September 2012 by using the terms 'trastuzumab emtansine (T-DM1) and anti-HER2 treatment'; papers which were considered relevant for the aim of this review were selected by the authors.
  
  
  RESULTS
  The phase III randomized trial EMILIA has shown that T-DM1 provided objective tumor responses and significantly improved progression free survival and overall survival compared to lapatinib and capacitabine combination in HER2-positive metastatic breast cancer patients treated with a prior taxane and trastuzumab regimen. It is believed that T-DM1 will play a role in the management of patients with advanced and early stage HER2-positive breast cancer, but this awaits further study. In particular, the ongoing phase III trials MARIANNE and TH3RESA will further give information about the place of T-DM1 in the treatment algorithms for HER2-positive disease.
  
  
  CONCLUSIONS
  The trials of T-DM1 as a single agent and in combination with other chemotherapies have shown clinical activity and a favorable safety profile in patients with HER2-positive metastatic breast cancer. There are ongoing studies of T-DM1 showing an increasing tendency towards moving the study of these agents to earlier stages of HER2-positive breast cancer.
authors: Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.
authors: Baris
authors: B
authors: Boyraz
authors: Mehmet A N
authors: MA
authors: Sendur
authors: Sercan
authors: S
authors: Aksoy
authors: Taner
authors: T
authors: Babacan
authors: Emir C
authors: EC
authors: Roach
authors: Muhammet C
authors: MC
authors: Kizilarslanoglu
authors: Ibrahim
authors: I
authors: Petekkaya
authors: Kadri
authors: K
authors: Altundag
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008453:Maytansine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D000068878:Trastuzumab; D016896:Treatment Outcome
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