Trastuzumab emtansine (T-DM1) for HER2-positive breast cancer.

Abstract

BACKGROUND:

Trastuzumab emtansine (T-DM1), a novel drug developed for the treatment of HER2-positive breast cancer, is a human epidermal growth factor receptor (HER2) targeted antibody drug conjugate, composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent DM1 (derivative of maytansine). It has been shown that, in preclinical studies, it has anti-tumor activity in trastuzumab refractory cancer cells. In this review, we aim to show the clinical data about trastuzumab-DM1 (T-DM1) therapy and to discuss the therapy advantages for the management of patients with HER2-positive breast cancer.

SCOPE:

T-DM1 showed positive results in clinical studies of HER2-positive metastatic breast cancer. PubMed database, ASCO and San Antonio Breast Cancer Symposium Meeting abstracts were searched up to September 2012 by using the terms 'trastuzumab emtansine (T-DM1) and anti-HER2 treatment'; papers which were considered relevant for the aim of this review were selected by the authors.

FINDINGS:

The phase III randomized trial EMILIA has shown that T-DM1 provided objective tumor responses and significantly improved progression free survival and overall survival compared to lapatinib and capacitabine combination in HER2-positive metastatic breast cancer patients treated with a prior taxane and trastuzumab regimen. It is believed that T-DM1 will play a role in the management of patients with advanced and early stage HER2-positive breast cancer, but this awaits further study. In particular, the ongoing phase III trials MARIANNE and TH3RESA will further give information about the place of T-DM1 in the treatment algorithms for HER2-positive disease.

CONCLUSION:

The trials of T-DM1 as a single agent and in combination with other chemotherapies have shown clinical activity and a favorable safety profile in patients with HER2-positive metastatic breast cancer. There are ongoing studies of T-DM1 showing an increasing tendency towards moving the study of these agents to earlier stages of HER2-positive breast cancer.

• Authors: Baris Boyraz, Mehmet A N Sendur, Sercan Aksoy, Taner Babacan, Emir C Roach, Muhammet C Kizilarslanoglu, Ibrahim Petekkaya, Kadri Altundag
• Journal: Current medical research and opinion (Curr Med Res Opin) Vol. 29 Issue 4 Pg. 405-14 (Apr 2013) ISSN: 1473-4877 [Electronic] England
• PMID: 23402224 (Publication Type: Journal Article, Review)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Maytansine
• ERBB2 protein, human
• Receptor, ErbB-2
• Trastuzumab
• Ado-Trastuzumab Emtansine

Topics

• Ado-Trastuzumab Emtansine
• Animals
• Antibodies, Monoclonal, Humanized (adverse effects, pharmacokinetics, therapeutic use)
• Antineoplastic Agents (adverse effects, pharmacokinetics, pharmacology, therapeutic use)
• Breast Neoplasms (chemistry, drug therapy)
• Disease-Free Survival
• Female
• Humans
• Maytansine (adverse effects, analogs & derivatives, pharmacokinetics, therapeutic use)
• Rats
• Receptor, ErbB-2 (analysis)
• Trastuzumab
• Treatment Outcome