Utilizing Trastuzumab Deruxtecan in HER2-Positive Breast Cancer

Hatem Soliman, MD, an associate member of the breast oncology program, and medical director of the clinical trials office, Moffitt Cancer Center, discusses fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) and its importance for patients with HER2-positive breast cancer.

According to Soliman, trastuzumab deruxtecan is a highly active antibody drug conjugate that has shown to be effective among patients with HER2-positive breast cancer. The agent first showed promise in the phase 1, single-arm trial (DESTINY-Breast01; NCT03248492) which evaluated trastuzumab deruxtecan in heavily-pretreated patients with HER2-positive breast cancer. These data led to the accelerated approval of T-DXd.

Then, the confirmatory DESTINY-Breast03 (NCT03529110) study explored T-DXd vs trastuzumab emtansine (Kadcycla; T-DM1), and most recently in 2022, findings from the DESTINY-Breast04 (NCT03734029) study continued to support the agent for the treatment of patients with HER2-low, hormone receptor–positive metastatic breast cancer.

TRANSCRIPTION:

0:08 | Trastuzumab deruxtecan is a game changer for us in the field. This is a very active drug, which showed its promise quite early on in its development based on some of the early DESTINY trials that were conducted. This drug is highly active, and it's an antibody drug conjugate. As opposed to the pertuzumab and trastuzumab-based treatments, which are just monoclonal antibodies, the antibody drug conjugate is a different way to deliver targeted chemotherapy payloads to the cells preferentially that overexpress or have a particular target while trying to spare the toxicity from normal tissues that don't express as much of the target.

1:02 | Trastuzumab deruxtecan tries to exploit that by taking those patients who are HER2-positive and delivering a highly potent payload known as SN-38, which is attached to the antibody. It's conjugated and gets sucked into the cells that overexpress HER2. Although nowadays, we use it for tumors that may have lower levels of HER2 expression as well with quite a bit of success. But the idea is still the same. The antibody gets sucked in, and then the chemical payload that's attached to the antibody gets cleaved off within the cell, and then it can go about doing its business of trying to knock off the target cell. That's what makes it so active and effective is the combination of that targeted delivery of a potent payload that allows it to have such a great level of activity in HER2-expressing cancers.