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Molecular Medicine

, Volume 18, Issue 11, pp 1473–1479 | Cite as

Trastuzumab-DM1: A Clinical Update of the Novel Antibody-Drug Conjugate for HER2-Overexpressing Breast Cancer

  • Myra F. Barginear
  • Veena John
  • Daniel R. Budman
Invited Review Article

Abstract

Trastuzumab is a monoclonal antibody targeted against the HER2 tyrosine kinase receptor. Although trastuzumab is a very active agent in HER2-overexpressing breast cancer, the majority of patients with metastatic HER2-overexpressing breast cancer who initially respond to trastuzumab develop resistance within 1 year of initiation of treatment and, in the adjuvant setting, progress despite trastuzumab-based therapy. The antibody-drug conjugate trastuzumab-DM1 (T-DM1) was designed to combine the biological activity of trastuzumab with the targeted delivery of a highly potent antimicrotubule agent, DM1 (N-methyl-N-(3-mercapto-1-oxopropyl)-L-alanine ester of maytansinol), a maytansine derivative, to HER2-overexpressing breast cancer cells. T-DM1 is the first antibody-drug conjugate with a nonreducible thioether linker in clinical trials. Phase I and II clinical trials of T-DM1 as a single agent and in combination with paclitaxel, docetaxel and pertuzumab have shown clinical activity and a favorable safety profile in patients with HER2-positive metastatic breast cancer. Two randomized phase III trials of T-DM1 are awaiting final results; the EMILIA trial is evaluating T-DM1 compared with lapatinib plus capecitabine, and early positive results have been reported. The MARIANNE trial is evaluating T-DM1 plus placebo versus T-DM1 plus pertuzumab versus trastuzumab plus a taxane. Here, we summarize evidence from clinical studies and discuss the potential clinical implications of T-DM1.

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Authors and Affiliations

  • Myra F. Barginear
    • 1
  • Veena John
    • 1
  • Daniel R. Budman
    • 1
  1. 1.Monter Cancer Center of the North Shore-Long Island Jewish (LIJ) Cancer InstituteHofstra North Shore-LIJ School of MedicineLake SuccessUSA

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