> Ado-Trastuzumab Emtansine Approved for Early-Stage, HER2-Positive Breast Cancer

Ado-Trastuzumab Emtansine Approved for Early-Stage, HER2-Positive Breast Cancer


FDA approves targeted treatment for people when disease remains after neoadjuvant therapy

The U.S. Food and Drug Administration on May 3 approved ado-trastuzumab emtansine (Kadcyla) to treat certain people with early-stage, HER2-positive breast cancers. The approval is based on results from the phase III KATHERINE trial, which were presented at the San Antonio Breast Cancer Symposium in December 2018.


Ado-trastuzumab emtansine, also known as TDM-1, is an antibody-drug conjugate. It links the HER2-targeted therapy trastuzumab (Herceptin) to a chemotherapy known as DM1. Trastuzumab attaches to cancer cells with too much of the HER2 protein. Because the medicine targets breast cancer cells in this way, it delivers chemotherapy mainly to cancer cells and is less harmful to healthy cells.

The FDA previously approved ado-trastuzumab emtansine for people with metastatic, HER2-positive breast cancer who already had treatment with trastuzumab and taxane chemotherapy. In early-stage breast cancer, trastuzumab is already approved with chemotherapy. Trastuzumab with chemotherapy can be used as neoadjuvant therapy, treatment given to shrink tumors before breast surgery.

If doctors still find breast cancer after neoadjuvant therapy, called residual disease, it may increase the chance that the cancer may return. Researchers wanted to see if using ado-trastuzumab emtansine after neoadjuvant therapy and surgery would lower the chance that the cancer would return.

The Approval

The FDA approved ado-trastuzumab emtansine to treat early-stage, HER2-positive breast cancer if doctors find residual disease at the time of surgery, after neoadjuvant therapy with trastuzumab-based treatment and chemotherapy. It is the first approval for ado-trastuzumab emtansine in early-stage breast cancer.

The approval was based on the phase III KATHERINE trial. In this trial, participants were given trastuzumab-based treatment and chemotherapy before surgery. If doctors saw signs of breast cancer at the time of surgery, the person was assigned to continue on trastuzumab alone or to get ado-trastuzumab emtansine.

The study found that people given ado-trastuzumab emtansine went longer without breast cancer returning, called invasive disease-free survival, than those who continued on trastuzumab alone. The findings were statistically significant, which means they were likely not the result of chance.

The study found that 3 years after treatment

  • 77 percent of people given trastuzumab did not have breast cancer return
  • 88 percent of people given ado-trastuzumab emtansine did not have breast cancer return

Ado-trastuzumab emtansine caused side effects in more people than trastuzumab alone, but researchers expected it would, and the results were similar to previous studies of this medicine. Some of the most common side effects were tiredness, nausea, low platelet counts, headaches, nose bleeds, sensory neuropathy (numbness and tingling sensation in fingers or toes), and high levels in some liver tests. Ado-trastuzumab emtansine also had more people stop treatment because of side effects:

  • 2 percent of people given trastuzumab stopped due to side effects.
  • 18 percent of people given ado-trastuzumab emtansine stopped due to side effects.

What This Means for You

The approval of ado-trastuzumab emtansine adds another tool for treating early-stage, HER2-positive breast cancer. If you were recently diagnosed with HER2-positive breast cancer, this may be an option for later treatment.

The treatment is recommended for people with residual disease after neoadjuvant therapy. If you are getting chemotherapy and trastuzumab-based treatment before surgery your doctors may not find residual disease. This means the chance of breast cancer returning is low for you, and you may not be offered ado-trastuzumab emtansine.

If your doctors find residual disease, it means there is a higher chance of breast cancer returning. But the KATHERINE trial found that ado-trastuzumab emtansine can lower that risk.

If you have questions about your treatment plan or your risk of breast cancer returning, speak to your medical team. They can explain why they recommended a certain treatment plan for your particular diagnosis.