T-DM1: A Novel and Effective Immunoconjugate for the Treatment of HER2+ Breast Cancer

Jiali Li, MD, Alexa Glencer, and Hope S. Rugo, MD
Published Online: January 8, 2013
Hope S. Rugo, MDCorresponding Author:

Hope S. Rugo, MD

Professor of Medicine and Director, Breast
Oncology and Clinical Trials Education,
University of California, San Francisco, Helen
Diller Family Comprehensive Cancer Center,
San Francisco, CA;


Trastuzumab-derivative of maytansine-1 (trastuzumab emtansine; T-DM1) is a novel antibody-drug conjugate that combines an antibody targeted specifically to HER2- overexpressing cancer cells with maytansine, a potent cytotoxic agent. In comparison with lapatinib and capecitabine in patients with trastuzumab-resistant HER2+ advanced breast cancer, treatment with T-DM1 resulted in improved progression-free and overall survival, with a superior safety profile. Ongoing clinical trials are investigating T-DM1-based therapy in combination with other chemotherapy agents, with other targeted agents, and as treatment for early-stage HER2+ breast cancer and other malignancies.

Between 20% and 25% of all breast cancers overexpress the HER2/neu receptor or have amplification of the HER2 (ErbB2) gene, with about half also expressing the estrogen receptor. Before the introduction of targeted therapy, HER2-expressing (HER2+) breast cancers were associated with a high risk of short-term recurrence and shorter overall survival (OS).1,2 Trastuzumab, a humanized monoclonal antibody targeting the HER2/neu receptor, was approved by the FDA in 1998 for the treatment of HER2+ metastatic breast cancer (mBC),3,4 and in 2006 for the treatment of early-stage disease. In the advanced-disease setting, trastuzumab administered as monotherapy exerts a modest antitumor effect but has marked synergistic antiproliferative effects when combined with cytotoxic agents.5-7

Although trastuzumab combined with chemotherapy has become the standard of care for the treatment of HER2+ mBC, up to 50% of patients present with de novo resistance.8 Progression-free survival (PFS) following treatment with trastuzumab combined with taxane-based chemotherapy is only about 1 year.9,10 PFS can be extended to about 18 months with the addition of pertuzumab, a novel HER2-targeted antibody approved in this setting by the FDA in June 2012.11 Chemotherapy combined with trastuzumab in the early-stage setting has significantly improved disease-free survival (DFS) and OS; however, relapses continue to occur even years after initial treatment.6,7,12 In addition, improved OS in both early- and late-stage disease with trastuzumab has been seen only when the antibody is given in combination with chemotherapy, and hence, concomitant chemotherapy toxicity.

Related Articles
Prudence Francis, MD, discusses the SOFT trial, which examined suppression of ovarian function, and the impact it could have on the future treatment of women under 35 with HR+ breast cancer.
Eric Van Cutsem, MD, PhD, discusses the challenges of using chemotherapy to treat patients with gastric cancer.
Acting two months ahead of its deadline, the FDA granted an accelerated approval to palbociclib (Ibrance) as a first-line treatment for patients with ER-positive metastatic breast cancer.
Metastatic disease accounts for the vast majority of cancer-related deaths. Ensuring a definitive diagnosis and the most effective treatment in a timely fashion is essential for extending life expectancy.
JTT Articles
BioT3 Integrates Diagnosis With Actionable Biomarkers in Metastatic Cancer
Immune Checkpoint Inhibitors for Renal Cell Carcinoma
External Resources

MJH Associates
Pharmacy Times
Specialty Pharmacy Times
Physicians' Education Resource
Internal Resources

Targeted Communications
Connect With Us:

About Us
Contact Us
Privacy Policy
Terms & Conditions
Intellisphere, LLC
666 Plainsboro Road
Building 300
Plainsboro, NJ 08536
P: 609-716-7777
F: 609-716-4747

Copyright TargetedOnc 2015
Intellisphere, LLC. All Rights Reserved.