T-DM1 Poised to Set New Standard in HER2-Positive Metastatic Breast Cancer

Silas Inman @silasinman
Published: Monday, Jul 14, 2014
Adam Brufsky, MD, PhD

Adam Brufsky, MD, PhD

The antibody-drug conjugate T-DM1 (ado-trastuzumab emtansine; Kadcyla) will have an impact on the entire spectrum of care for patients with metastatic HER2-positive breast cancer, resulting in a greater emphasis on patient selection protocols and testing, according to the expert panelists in a recent Peer Exchange discussion.

T-DM1, which was first approved by the FDA in February 2013, is being explored in several settings as a single agent and in combinations for patients with HER2-positive metastatic breast cancer. Additionally, studies are exploring biomarkers of response that may provide clues for selecting optimal treatments. In general, many of these studies are ongoing or have recently been presented, noted Adam M. Brufsky, MD, PhD, in the recent OncLive Peer Exchange roundtable entitled “Practical Considerations in Breast Cancer.

Multiple Trials Focus on T-DM1

The approval of T-DM1 was based on results from the phase III EMILIA trial1 that randomized 991 patients with HER2-positive advanced breast cancer previously treated with trastuzumab (Herceptin) and a taxane in a 1:1 ratio to T-DM1 or lapatinib (Tykerb) plus capecitabine. Overall, treatment with T-DM1 resulted in a median progression- free survival (PFS) of 9.6 months versus 6.4 months with lapatinib/capecitabine. The median overall survival (OS) was 30.9 months for T-DM1 versus 25.1 months for lapatinib/ capecitabine.

Moreover, T-DM1 was associated with fewer adverse events (AEs). Grade 3 or higher AEs occurred in 57% of patients in the lapatinib/capecitabine arm compared with 41% for the T-DM1 arm. “This is an ongoing open-label study with some very significant results reported and by every measure used,” said Brufsky. “T-DM1 had a greater efficacy and less toxicity than combined lapatinib and capecitabine.”


Adam M. Brufsky, MD, PhD
Medical Director
Women’s Cancer Center
Magee-Womens Hospital of UPMC
University of Pittsburgh Cancer Institute
Pittsburgh, PA


Kimberly L. Blackwell, MD
Professor, Medicine
Assistant Professor Radiation Oncology
Duke Cancer Institute
Durham, NC

Joyce A. O’Shaughnessy, MD
Co-Director Breast Cancer Research Baylor
Charles A. Sammons Cancer Center
Texas Oncology/The US Oncology Network
Dallas, TX

Mark D. Pegram, MD
Professor, Medicine (Oncology)
Stanford University Medical Center
Associate Director, Clinical Research
Director, Breast Cancer Program
Stanford Cancer Institute
Stanford, CA

Hope S. Rugo, MD
Professor, Medicine
Breast Oncology Clinical Trials Program
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, CA

Denise A. Yardley, MD
Senior Investigator
Breast Cancer Research
Sarah Cannon Research Institute
Tennessee Oncology
Nashville, TN
Data from the phase III TH3RESA study2 were presented at the 2013 European Cancer Congress. This study randomized 602 patients with advanced HER2-positive breast cancer previously treated with at least two HER2-directed therapies in a 2:1 ratio to receive T-DM1 or physician’s choice of treatment. The administration of T-DM1 resulted in a median PFS of 6.2 months compared with 3.3 months in the control arm. The median OS findings are not yet available. “What data we have is that both in EMILIA and in TH3RESA, the T-DM1 should be the goto agent,” said Kimberly L. Blackwell, MD. “EMILIA and TH3RESA really suggest that T-DM1 should play a major role in the treatment of HER2- positive, trastuzumab-refractory metastatic breast cancer.”

Building upon these results, the phase III MARIANNE trial3 is examining T-DM1 plus or minus pertuzumab (Perjeta) compared with trastuzumab plus a taxane for recurrent locally advanced or untreated patients with HER2-positive metastatic breast cancer. Although results have not yet been presented, experts expect this trial to establish T-DM1 as the first-line standard of care. In addition to demonstrating the overall efficacy of T-DM1 in the frontline setting, the MARIANNE trial will establish whether the addition of pertuzumab to T-DM1 improves efficacy.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Clinical Interchange™: Translating Research to Inform Changing Paradigms: Assessment of Emerging Immuno-Oncology Strategies and Combinations across Lung, Head and Neck, and Bladder CancersOct 31, 20182.0
Community Practice Connections: Oncology Best Practice™ Targeting Cell Cycle Progression: The Latest Advances on CDK4/6 Inhibition in Metastatic Breast CancerOct 31, 20181.0
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