The KATHERINE trial studied a new use for ado-trastuzumab emtansine, also known as TDM-1 or Kadcyla. This medicine links the HER2-targeting therapy trastuzumab (Herceptin) to a chemotherapy medicine that is too toxic to be given on its own. TDM-1 is already FDA approved to treat metastatic HER2-positive breast cancer.

KATHERINE tested whether TDM-1 could benefit some people with early-stage disease as well. The trial looked at people who had residual disease, or cancer cells that remain despite treatment with chemotherapy and trastuzumab before surgery. Residual disease is linked to higher risk for recurrence and death.

Everyone in KATHERINE received chemotherapy and HER2-targeting therapy before surgery. If doctors found at least one centimeter of disease remaining after surgery, participants were randomly assigned to get 14 cycles of either trastuzumab or TDM-1. The researchers wanted to see which medicine had a greater effect on invasive disease-free survival, or how long people went without having a recurrence of invasive breast cancer.

The difference between the two groups was statistically significant, meaning it is not likely the result of chance. After following participants for about 3 years:

• 77 percent of those taking trastuzumab went without a recurrence.
• 88 percent of people taking TDM-1 went without a recurrence.

Researchers will continue to follow up to see whether this effect extends to overall survival, a measure that will take more time to show. But the findings will likely change practice immediately for people with residual disease after pre-surgery chemotherapy, said Eric Winer, MD, of Dana-Farber Cancer Institute in Boston and a member of LBBC’s Medical Advisory Board. Dr. Winer led a plenary discussion after the trial was presented. He declared on one of his slides, in large red letters, “The Standard of Care Has Changed” for this group.

Also presented Wednesday morning was the IMpassion130 trial of the immunotherapy atezolizumab (Tecentriq). When first announced in October at the European Society for Medical Oncology Annual Congress, the results drew worldwide attention and discussion. Participants received atezolizumab and the chemotherapy nab-paclitaxel (Abraxane) as their first treatment for metastatic triple-negative breast cancer. The study showed an increase in progression-free survival—the first time that had ever been shown in this type of cancer with an immunotherapy medicine. But the benefit was mostly limited to people with immune cells near the tumor that expressed PD-L1. The study also showed a trend toward higher overall survival, but it was too early to see a benefit (or lack of benefit) across the entire group.

Yesterday’s presentation took a deeper look at features of different groups in the study to see whether it’s possible to tell who can be helped by this treatment. These data reinforced earlier findings that PD-L1 expression is the best way to predict who will benefit from using atezolizumab. Testing positive for PD-L1 expression predicted that atezolizumab could help extend progression-free survival, or how long a person lives without the cancer growing. That represented about 40 percent of those in the study. The tumors of these people had some T-cells, white blood cells that help the immune system fight cancer, so tested positive for PD-L1. For people whose cancers tested negative for PD-L1, adding atezolizumab did not change progression-free survival.

During an evening Hot Topics session sponsored by the Alamo Breast Cancer Foundation, medical oncologist Julie Gralow, MD, explained that anyone whose cancers tested positive for PD-L1 appeared to benefit from the immunotherapy combination, no matter how much or how few T-cells they had. Dr. Gralow, who practices at Seattle Cancer Care Alliance and is a member of LBBC’s Medical Advisory Board, said she expects atezolizumab to be FDA approved based upon the findings presented over the last few months.