> Trastuzumab deruxtecan shows high response rates in phase II trial

Trastuzumab deruxtecan shows high response rates in phase II trial


While early results are impressive, more research is needed

Trastuzumab durextecan (Enhertu) was FDA approved in December 2019. This article explains the research that helped support the initial FDA approval. 

Results from the phase II DESTINY-Breast01 trial studying the new antibody drug conjugate trastuzumab deruxtecan, also called DS-8201, were presented Wednesday at the San Antonio Breast Cancer Symposium and released the same day in the New England Journal of Medicine. The presentation showed very positive results in overall response rate for people with metastatic, HER2-positive breast cancer, but more research is necessary to see if trastuzumab deruxtecan helps people live longer than treatments currently available.

Antibody drug conjugates link chemical medicines that kill cells to antibodies that target features of cancer cells, in this case the HER2-receptor. The idea is to bring more powerful medicines to cancer cells and harm fewer healthy cells in the process. The notable antibody drug conjugate in use for breast cancer treatment currently is ado-trastuzumab emtansine (Kadcyla). Newer antibody drug conjugates, such as trastuzumab deruxtecan, are designed to carry more of the medicine part and researchers hope that will make for even better outcomes.

DESTINY-Breast01 was an open-label trial, meaning doctors and the women being treated knew that trastuzumab deruxtecan was being given, and everyone in the trial received the treatment. The study included 184 women with metastatic, HER2-positive breast cancer that had previously been treated with trastuzumab and ado-trastuzumab emtansine.


The study found that tumors responded in 60.9 percent of women given trastuzumab deruxtecan. The median response duration, or length of time that a tumor continues to respond to treatment without growing or traveling to another part of the body, was 14.8 months. The median duration of progression-free survival, or the length of time a person lives without cancer growing or spreading, was 16.4 months.

The most common side effects for those participating in the trial were nausea, vomiting, and fatigue. Trastuzumab deruxtecan was also associated with interstitial lung disease (ILD), a scarring or inflammation of certain lung tissue. In this study, 13.3 percent of participants developed ILD, and four women (2.2 percent of participants) died from it. Researchers said this should be closely watched in future studies, with guidance on identifying ILD and the recommendation to treat with steroids the moment ILD is suspected.

What this means for you

Though DESTINY-Breast01 is a phase II trial, the high response rate and long duration of response brought a lot of attention. The women in this trial had already been through two lines of treatment, so it is exciting to see that, on average, the cancer responded to this treatment for over a year. However, further testing in a randomized trial will need to be done to see how trastuzumab deruxtecan compares to current treatment options. Doctors will also want to learn more about interstitial lung disease as a side effect and how well it is managed in larger populations.