The EMILIA study found that women diagnosed with locally advanced or metastatic HER2-positive breast cancer that had stopped responding to a standard targeted therapy regimen lived longer without the cancer growing when they got the experimental medicine T-DM1 (chemical name: ado-trastuzumab emtansine) compared to women who got a different targeted therapy regimen.
The findings were reported at the 2012 American Society of Clinical Oncology Annual Meeting. Read the abstract of Primary results from EMILIA, a phase III study.
T-DM1 is a combination of the targeted therapy medicine Herceptin (chemical name: trastuzumab) and the chemotherapy medicine emtansine. In T-DM1, the emtansine is attached to the Herceptin.
(In earlier studies on T-DM1, it was reported that the chemotherapy medicine maytansine was attached to Herceptin to form T-DM1. Emtansine is a derivative of maytansine.)
Herceptin is approved by the U.S. Food and Drug Administration to treat advanced-stage, HER2-positive breast cancers and to lower the risk of recurrence of early-stage, HER2-positive breast cancer with a high risk of recurrence. HER2-positive cancers make too much of the HER2 protein. The HER2 protein sits on the surface of cancer cells and receives signals that tell the cancer to grow and spread. About one out of every four breast cancers is HER2-positive. Herceptin works by attaching to the HER2 protein and blocking it from receiving growth signals.
Emtansine, like some other chemotherapy medicines, disrupts the way cells grow. Emtansine isn't a targeted medicine, which means it can affect healthy cells as well as cancer cells.
T-DM1 was designed to deliver emtansine to cancer cells in a targeted way by attaching emtansine to Herceptin. Herceptin then carries emtansine to the HER2-positive cancer cells.
Locally advanced breast cancer is cancer that has spread to the chest wall below or the skin above the breast. Metastatic breast cancer is cancer that has spread to other parts of the body away from the breast, such as the bones or liver.
The EMILIA study looked at 991 women diagnosed with locally advanced or metastatic HER2-positive breast cancer that had stopped responding to a standard treatment regimen of Herceptin and a taxane chemotherapy. Paclitaxel (brand name: Taxol), albumin-bound or nab-paclitaxel (brand name: Abraxane), and docetaxel (brand name: Taxotere) are taxanes.
The women were randomly assigned to receive one of two treatment regimens:
- half the women got a combination of the targeted therapy Tykerb (chemical name: lapatinib) and the chemotherapy Xeloda (chemical name: capecitabine); this combo already is approved to treat advanced-stage HER2-positive breast cancer that has stopped responding to Herceptin
- half the women got T-DM1
Half the women were followed for more than a year and the other half were followed for shorter times.
Progression-free survival -- the time the women lived without the cancer growing -- was 9.6 months in women treated with T-DM1 compared to 6.4 months in women treated with Tykerb and Xeloda.
The study also found other important differences between the two treatment groups:
- 84.7% of women who got T-DM1 were alive after a year compared to 77% who got the Tykerb-Xeloda combination
- 65.4% of women who got T-DM1 were alive after 2 years compared to 47.5% who got the Tykerb-Xeloda combination
These results seem promising; still, more follow-up time is needed before researchers can judge whether overall survival will be better with T-DM1.
The treatment stopped the cancer from growing for a time in some women and the cancer actually shrank in other women:
- 43.6% of women who got T-DM1 had this response compared to 30.8% who got the Tykerb-Xeloda combination
The time that passed before cancer-related symptoms got worse was longer (7.1 months vs. 4.6 months) in women who got T-DM1 compared to women who got the Tykerb-Xeloda combination.
Severe side effects are unfortunately common with many cancer treatments. About 41% of women who got T-DM1 had severe side effects compared to 57% of women who got the Tykerb-Xeloda combination.
The results suggest that T-DM1 could be an important new treatment option for women diagnosed with advanced-stage, HER2-positive breast cancer. The women in the EMILIA study will continue to be followed to see if T-DM1 improves overall survival.
Another study (the MARIANNE study) is looking to see if T-DM1 would be effective as the first targeted therapy treatment given to women diagnosed with advanced-stage, HER2-positive breast cancer. And a third study (the TH3RESA study) is looking at whether T-DM1 could treat advanced-stage, HER2-positive breast cancer that has stopped responding to both Herceptin and Tykerb.
If you've been diagnosed with locally advanced or metastatic HER2-positive breast cancer, you and your doctor may be considering a number of treatment options. If you're willing to participate in a clinical trial, you may have even more options available, possibly including an experimental medicine such as T-DM1. Talk to your doctor about clinical trials that might be a good fit for you and your unique situation. Visit the Breastcancer.org Clinical Trials pages for more information.
And stay tuned to Breastcancer.org for updates on research using T-DM1 to treat HER2-positive breast cancer.
Editor’s Note: On Feb. 22, 2013, the U.S. Food and Drug Administration (FDA) approved Kadcyla (chemical name: T-DM1 or ado-trastuzumab emtansine). In some early studies of T-DM1, such as the study reviewed here, it was reported that the chemotherapy medicine maytansine was attached to Herceptin to form T-DM1. Emtansine is a derivative of maytansine. On May 3, 2019, the FDA approved Kadcyla to treat early-stage HER2-positive breast cancer after surgery if residual disease was found after neoadjuvant treatment with taxane chemotherapy and Herceptin.