Treatment of HER2 positive advanced breast cancer with T-DM1: A review of the literature

Crit Rev Oncol Hematol. 2016 Jan;97:96-106. doi: 10.1016/j.critrevonc.2015.08.011. Epub 2015 Aug 11.

Abstract

Background: Trastuzumab emtansine (T-DM1), a new agent developed for the treatment of HER2-positive breast cancer, is an antibody-drug conjugate with a complex compound obtained by the conjugation of trastuzumab, a stable thioether linker, and the potent cytotoxic drug maytansine-derivate(DM1), which inhibits cell division and induces cell death.

Field of study: PubMed database, ESMO, ASCO, San Antonio Breast Cancer Symposium Meeting abstracts and clinicaltrials.gov were searched using the terms "Anti-HER2 treatment breast cancer and trastuzumab emtansine (T-DM1) "; papers considered relevant for the aim of this review were selected.

Findings/results: The phase I trials have determined the safe dosing range of T-DM1, established at 3.6 mg/kg every 3 weeks. The phase III randomized EMILIA and TR3RESA trials have shown that T-DM1 provides objective tumor responses and significantly improves progression free survival and overall survival in HER2-positive metastatic breast cancer patients previously treated with anti-HER2-based regimens. The ongoing phase III trials KAITLIN and KATHERINE will give us further information about the place T-DM1 should occupy in the treatment of patients with early stage HER2-positive breast cancer. In this review we analyze the most relevant clinical trials conducted with T-DM1 and the role of this compound in the management of advanced breast cancer.

Conclusion: T-DM1 has shown clinically relevant activity in the treatment of HER2-positive breast cancer patients after progression on trastuzumab and taxane based therapy, both in the second line treatment setting and after early relapse on adjuvant trastuzumab therapy. This is accompanied by a favorable safety and tolerability profile.

Keywords: Advanced Breast cancer; Her2 positive; Trastuzumab emtansine; Treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Ado-Trastuzumab Emtansine
  • Antibodies, Monoclonal, Humanized / chemistry
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Clinical Trials, Phase III as Topic
  • Disease Progression
  • Female
  • Humans
  • Maytansine / analogs & derivatives*
  • Maytansine / chemistry
  • Maytansine / pharmacokinetics
  • Maytansine / therapeutic use
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / metabolism
  • Receptor, ErbB-2 / metabolism*
  • Trastuzumab

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Maytansine
  • Receptor, ErbB-2
  • Trastuzumab
  • Ado-Trastuzumab Emtansine