title: Trastuzumab emtansine: a novel antibody-drug conjugate for HER2-positive breast cancer.
abstract: Trastuzumab emtansine (T-DM1) is a novel HER2-directed antibody-drug conjugate. T-DM1 consists of the potent antimicrotubule agent DM1, linked via a noncleavable linker to the HER2-specific monoclonal antibody trastuzumab. Preclinical studies demonstrate that T-DM1 has dual mechanisms of action: selective delivery of DM1 to the HER2-positive (HER2(+)) tumor cell combined with trastuzumab's activation of antibody-dependent cell-mediated cytotoxicity and inhibition of HER2-mediated signal transduction. In phase II studies, T-DM1 was active in patients with trastuzumab- and lapatinib-refractory metastatic breast cancer and led to improved progression-free survival compared with the combination of trastuzumab and docetaxel in the first-line setting. In a recent phase III trial in patients with metastatic breast cancer who previously received trastuzumab and a taxane, T-DM1 resulted in improved progression-free and overall survival compared with capecitabine and lapatinib. T-DM1 is associated with a favorable toxicity profile; reversible thrombocytopenia and hepatic transaminase elevations are the only grade ≥3 adverse event present in 5% or more of patients. Alopecia, peripheral neuropathy, and neutropenia are distinctly uncommon. On the basis of its improved efficacy and toxicity compared with capecitabine/lapatinib, T-DM1 should be considered the standard for patients with HER2(+) metastatic breast cancer who have previously progressed on trastuzumab and a taxane. Results from additional randomized studies in metastatic breast cancer are pending, and trials in the (neo)adjuvant setting are being initiated.
authors.affiliation: Authors' Affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Ian
authors.initials: I
authors.lastname: Krop
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008453:Maytansine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; 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