title: [Antibody-drug conjugates in oncology: from the concept to trastuzumab emtansine (T-DM1)].
abstract: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) which associates the selective intracellular targeting of the cytotoxic agent, DM1 (maytansine derivative) to the antitumor activity of trastuzumab. T-DM1 targets the epidermal growth factor receptor 2 (HER2), highly expressed in the most aggressive forms of breast cancer. Current standard of care in HER2-positive advanced or metastatic breast cancers has its limitations, particularly after progression on HER2-targeted approved therapies. T-DM1 showed a significant antitumor activity in vitro and in vivo, and in experimental models resistant to HER2-targeted agents. Phase I and II studies showed that the maximum tolerated dose for T-DM1 is 3.6 mg/kg given intravenously every three weeks. At this recommended dose, T-DM1 provided objective tumor responses and favourable safety profile. A phase II randomised study, evaluating T-DM1 in first line vs trastuzumab plus docetaxel, the current standard of care in advanced or metastatic breast cancers, showed improved tolerability and efficacy. Recently, the results of EMILIA, a phase III randomised study assessing, after prior treatment with trastuzumab and a taxane, the efficacy and the safety of T-DM1 vs lapatinib plus capecitabine, confirmed the therapeutic benefit. T-DM1 appears to be an effective therapeutic option to treat patients with HER2-positive metastatic breast cancer.
authors.affiliation: Institut Paoli-Calmettes, oncologie médicale, 232, boulevard Sainte-Marguerite, 13009 Marseille, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Gonçalves
authors.forename: Olivier
authors.initials: O
authors.lastname: Trédan
authors.forename: Christian
authors.initials: C
authors.lastname: Villanueva
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000009:adverse effects / Q000627:therapeutic use*; D008453:Maytansine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000922:Immunotoxins; D008453:Maytansine; D000068878:Trastuzumab; D000080044:Ado-Trastuzumab Emtansine