Trastuzumab emtansine: first global approval

Drugs. 2013 May;73(7):755-65. doi: 10.1007/s40265-013-0050-2.


Genentech and ImmunoGen are collaborating on the development of trastuzumab emtansine, a HER2 antibody-drug conjugate that comprises Genentech's trastuzumab antibody linked to ImmunoGen's anti-mitotic agent, mertansine (a maytansine derivative; also known as DM1). The conjugate combines two strategies: the anti-HER2 activity of trastuzumab, and the targeted intracellular delivery of mertansine, a tubulin polymerisation inhibitor which interferes with mitosis and promotes apoptosis. The linker in trastuzumab emtansine is a non-reducible thioether linker, N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC, designated MCC after conjugation). Trastuzumab emtansine (Kadcyla™) has been launched in the USA as second-line monotherapy for HER2-positive metastatic breast cancer, and has been filed for approval in the EU and Japan in this indication. Trastuzumab emtansine is in phase III development as first-line combination therapy or monotherapy for metastatic HER2-positive breast cancer, and as third-line monotherapy for metastatic HER2-positive breast cancer. Phase II development is underway for early-stage breast cancer and phase II/III development is underway in patients with HER2-positive gastric cancer. This article summarizes the milestones in the development of trastuzumab emtansine leading to this first approval for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination.

Publication types

  • Review

MeSH terms

  • Ado-Trastuzumab Emtansine
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Drug Approval*
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use*
  • Female
  • Humans
  • Maytansine / adverse effects
  • Maytansine / analogs & derivatives*
  • Maytansine / pharmacology
  • Maytansine / therapeutic use
  • Trastuzumab


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Drugs, Investigational
  • Maytansine
  • Trastuzumab
  • Ado-Trastuzumab Emtansine