A Closer Look at T-DXd in HER2-Positive Breast Cancer

Sarah Sammons, MD, medical oncologist, clinical investigator in the Breast Oncology Center, associate director of the Metastatic Breast Cancer Program, Dana-Farber Cancer Institute, provides an overview of the DESTINY-Breast03 trial (NCT03529110).

Sammons was an investigator on an exploratory analysis of the randomized, multicenter, phase 3 DESTINY-Breast03 trial which highlighted the need to evaluate trastuzumab deruxtecan (Enhertu; T-DXd), an antibody drug conjugate, for the treatment of patients with HER2-low breast cancer, active HER2-positive breast cancer, and other solid tumors expressing brain metastases.

In the study, experts compared T-DXd with older ADCs like T-DM1 (trastuzumab emtansine; Kadcyla).

Transcription:

0:09 | I can tell you a little bit about the DESTINY-Breast03 clinical trial. I was not a primary investigator, but I am very aware of the data and happy to talk about the trial because it has had major implications for our patients with HER2-positive metastatic breast cancer. The DESTINY-Breast03 clinical trial was a randomized, multicenter, phase 3 clinical trial that looked at comparing trastuzumab deruxtecan, or T-DXd, with an older antibody-drug conjugates called T-DM1, or trastuzumab emtansine [Kadcyla].

0:51 | This was an important trial that established the new standard-of-care treatment for our patients with metastatic HER2-positive breast cancer in the second-line setting after treatment with a taxane and trastuzumab [Herceptin]/pertuzumab [Perjeta]. Patients in this clinical trial who had already received first-line therapy were randomized to either T-DXd, which is a new antibody-drug conjugate, or T-DM1, which is an older antibody-drug conjugate.

1:21 | We have seen the primary results of this clinical trial a while ago, and it was a dramatically positive clinical trial. Those patients that got T-DXd had a progression-free survival of almost 29 months, which is really just unprecedented in the first- or second-line HER2-positive metastatic setting vs about 7 months with T-DM1, so almost a 4-fold improvement in progression-free survival. We have also seen overall survival benefits in the second-line overall population.