HER2 Directed Antibody-Drug-Conjugates beyond T-DM1 in Breast Cancer

Int J Mol Sci. 2019 Mar 5;20(5):1115. doi: 10.3390/ijms20051115.


Since the discovery of the human epidermal growth factor receptor 2 (HER2) as an oncogenic driver in a subset of breast cancers and the development of HER2 directed therapies, the prognosis of HER2 amplified breast cancers has improved meaningfully. Next to monoclonal anti-HER2 antibodies and tyrosine kinase inhibitors, the antibody-drug conjugate T-DM1 is a pillar of targeted treatment of advanced HER2-positive breast cancers. Currently, several HER2 directed antibody-drug conjugates are under clinical investigation for HER2 amplified but also HER2 expressing but not amplified breast tumors. In this article, we review the current preclinical and clinical evidence of the investigational drugs A166, ALT-P7, ARX788, DHES0815A, DS-8201a, RC48, SYD985, MEDI4276 and XMT-1522.

Keywords: (vic-)trastuzumab duocarmazine; ADC; HER2 low; HM2-MMAE; TAK-522; Trastuzumab deruxtecan; Trastuzumab emtansine; anti-HER2/PBD-MA; mode of action.

Publication types

  • Review

MeSH terms

  • Ado-Trastuzumab Emtansine
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Clinical Trials as Topic
  • Female
  • Humans
  • Maytansine / analogs & derivatives*
  • Maytansine / therapeutic use
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptor, ErbB-2 / metabolism*
  • Trastuzumab / therapeutic use*


  • Antineoplastic Agents, Immunological
  • Protein Kinase Inhibitors
  • Maytansine
  • Receptor, ErbB-2
  • Trastuzumab
  • Ado-Trastuzumab Emtansine