Final Results of TH3RESA Trial Confirm Effectiveness of T-DM1

Breast Cancer News
October 17, 2014
Erin Rowley, Writer and Content Coordinator
Reviewed By: 
Nicholas J. Robert, MD

Final results of the phase III TH3RESA trial confirm that the medicine T-DM1 extends progression-free survival, PFS, in people who have HER2-positive metastatic breast cancer that no longer responds well to first-line treatments, such as trastuzumab. PFS is the time from the start of treatment until the disease grows or spreads.

Early results of this study were presented at the European Cancer Congress, in Amsterdam, in the fall of 2013.

Background and Goals

About one-fifth of breast cancers are HER2-positive, meaning the tumors grow because they have too much of a protein called human epidermal growth factor receptor-2, HER2. Targeted therapies such as trastuzumab (Herceptin), which can hone in on the cancer cells rather than treat the whole body, are effective in treating HER2-positive disease. However, they sometimes stop working over time.

Ado-trastuzumab emtansine (Kadcyla), also known as T-DM1, is an antibody drug conjugate, a cancer treatment that pairs chemotherapy medicines with targeted therapies. Pairing the two medicines delivers the chemotherapy to tumor cells directly and lessens harmful effects on healthy cells.

A past study, the EMILIA trial, found that compared to capecitabine (Xeloda) and lapatinib (Tykerb), T-DM1 did a better job of extending overall survival, OS, the time from the start of treatment to death from any cause, for women with HER2-positive metastatic breast cancer who were no longer benefiting from other treatments. This led to FDA approval of T-DM1. To build on this information, the TH3RESA trial compared T-DM1 to standard breast cancer treatments.


More than 600 people with metastatic, HER2-positive breast cancer took part in TH3RESA. They all had cancer that continued to grow despite treatment with any two of the following medicines: trastuzumab, lapatinib, or a taxane, chemotherapy that blocks cell growth by stopping cell division.

Participants were randomly assigned to one of two groups. One group received the study medicine, T-DM1, by vein every 3 weeks. The other group received standard treatments chosen by their doctors.

The researchers measured and compared OS and PFS.


The final results showed that

  • Median PFS lasted almost 3 months longer in the T-DM1 group
  • 31 percent of participants in the T-DM1 group saw their cancer shrink after treatment, versus 9 percent in the standard treatment group
  • The standard treatment group experienced 2 percent more serious side effects than the T-DM1 group

The data also suggested T-DM1 may lengthen OS. The researchers will report on OS at a later date.

TH3RESA researchers say that based on these results, T-DM1 should become a standard treatment for people with HER2-positive metastatic breast cancer that has progressed despite treatment with other medicines.

What This Means for You

If you have HER2-positive metastatic breast cancer and the standard treatments have stopped working as well for you, you may feel frustrated and out of options. This research shows that T-DM1 may be another option to control the disease longer and with fewer side effects.

Multiple trials are currently recruiting people for more studies of T-DM1. If you are interested in participating, visit and talk to your doctor.

Krop, Ian; Kim, Sung-Bae; González-Martín, Antonio et al. Trastuzumab emtansine versus treatment of physician’s choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. The Lancet. June 2014; doi:10.1016/S1470-2045(14)70178-0.

Additional Related Topics 
Clinical Trials