title: Ado-trastuzumab emtansine: a HER2-positive targeted antibody-drug conjugate.
abstract: OBJECTIVE
  To review the pharmacology, pharmacokinetics, efficacy, adverse effects, drug-drug interactions, dosage and administration, and formulary considerations for ado-trastuzumab emtansine.
  
  
  METHODS
  Sources of information were identified through a PubMed search (1966 to June 2014) using the key terms ado-trastuzumab emtansine, trastuzumab-DM1, trastuzumab-MCC-DM1, and T-DM1. Other information was obtained from clinicaltrials.gov, product labeling, and press releases.
  
  
  METHODS
  All English-language clinical trials and abstracts evaluating ado-trastuzumab emtansine in humans were reviewed for inclusion.
  
  
  RESULTS
  Overexpression or amplification of human epidermal growth factor receptor 2 (HER2) occurs in approximately 20% of breast cancers and is associated with more aggressive tumors and poorer prognosis in the absence of treatment. Although effective therapies for the initial management of HER2-positive metastatic breast cancer (MBC) exist, many patients will experience disease progression. Most second-line therapies are associated with either significant toxicities or limited improvements in overall survival (OS). Ado-trastuzumab emtansine is a HER2-positive directed antibody drug conjugate (ADC) approved in February 2013. In phase III clinical trials comparing the efficacy and safety of ado-trastuzumab emtansine with lapatinib-capecitabine or physician's choice, ado-trastuzumab emtansine had a better tolerability profile and improved progression-free survival compared with lapatinib-capecitabine or physician's choice and increased OS compared with lapatinib-capecitabine.
  
  
  CONCLUSIONS
  Ado-trastuzumab emtansine is a novel ADC effective for HER2-positive MBC in patients previously treated with trastuzumab, lapatinib, and a taxane. Further studies will determine its use in the adjuvant and neoadjuvant setting and in combination with pertuzumab.
authors.affiliation: Virginia Commonwealth University Health System, Richmond, VA, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Corrigan
authors.affiliation: Virginia Commonwealth University Health System, Richmond, VA, USA.
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Cicci
authors.affiliation: Virginia Commonwealth University Health System, Richmond, VA, USA.
authors.forename: Jessica Johnston
authors.initials: JJ
authors.lastname: Auten
authors.affiliation: Virginia Commonwealth University Health System, Richmond, VA, USA dlowe@mcvh-vcu.edu.
authors.forename: Denise K
authors.initials: DK
authors.lastname: Lowe
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000069287:Capecitabine; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077341:Lapatinib; D008453:Maytansine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D011799:Quinazolines / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D043823:Taxoids / Q000627:therapeutic use; D000068878:Trastuzumab
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D018796:Immunoconjugates; D000077341:Lapatinib; D008453:Maytansine; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C485206:pertuzumab
keywords: breast cancer; cancer; chemotherapy; drug development and approval; oncology