Expanded Roles for Trastuzumab Deruxtecan in HER2+ Breast Cancer

Erika P. Hamilton, MD, director of the Breast and Gynecologic Cancer Research Program at the Sarah Cannon Research Institute and medical oncologist at Tennessee Oncology, discusses the wide-ranging impacts of the introduction of fam-trastuzumab deruxtecan-nxki (Enhertu) for patients with HER2-positive breast cancer.

Hamilton says that the success of trastuzumab deruxtecan in the phase 3 DESTINY-Breast03 study (NCT03529110) has led to its approval for HER2-positive breast cancer. In addition, it was also approved in HER2-positive gastric or gastroesophageal carcinoma based on the DESTINY-Gastric01 trial (NCT03329690) and for HER2-low breast cancer based on the DESTINY-Breast04 trial.

These trials have demonstrated the potential of antibody-drug conjugates (ADCs) as a targeted method for delivering cytotoxic payloads into cancer cells while avoiding toxicity toward healthy cells, according to Hamilton.

Additionally, there are other ADCs in development in breast cancer with different targets including HER3 ADCs and a TROP2-directed ADC. New ADCs are also showing potential in other disease types. Hamilton is also investigating DS-6000a, a CDH6 ADC for renal cell carcinoma (RCC) and ovarian cancer, in a phase 1 clinical trial (NCT04707248).

TRANSCRIPTION:

0:08 | I think that trastuzumab deruxtecan was a massive win and we're seeing that in HER2-positive breast cancer. We are seeing it in areas like gastrointestinal cancers, or the ASCO [American Society of Clinical Oncology] plenary, even patients that have HER2-low breast cancers. I think this provides more excitement for ADCs as a way to get powerful payload or chemotherapy into the cancer cells while trying to spare a lot of the normal body through the ADC platform.

We know that there are some similar ADCs in terms of platform and structure coming, some HER3 ADCs, a new TROP2 ADC, as well in some other cancers, such as a CDH6 ADC that is being looked at in RCC and ovarian cancer.