Dr Graff on the Evaluation of Trastuzumab Deruxtecan in HER2-Zero Breast Cancer

Stephanie L. Graff, MD, director, breast oncology, Lifespan Cancer Institute, assistant professor of medicine, Warren Alpert Medical School, co-leader, Breast Cancer Translational Research Disease Group, Brown University’s Legorreta Cancer Center, discusses the evaluation of fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with HER2-zero metastatic breast cancer in the ongoing, phase 2 DESTINY-Breast06 trial (NCT04494425).

In the ongoing DESTINY-Breast06 trial, investigators are exploring the use of the antibody-drug conjugate (ADC) vs physician’s choice of chemotherapy in patients with hormone receptor–positive/HER2-low breast cancer who have progressed on prior endocrine therapy in the metastatic setting. As a part of the trial, investigators are aiming to accrue and evaluate a small subgroup of patients who are HER2-zero, Graff explains. HER2-zero, meeting the lowest possible definition of HER2 expression, Graff adds.

Based on the portfolio of DESTINY-Breast trials that have evaluated trastuzumab deruxtecan, there extensive positive data on how the ADC performs in patients with HER2-positve disease. Additionally, in August 2022, the FDA approved trastuzumab deruxtecan for the treatment of patients with unresectable or metastatic HER2-low breast cancer, based on data from the phase 3 DESTINY-Breast04 trial (NCT03734029).

Investigators have some data and understanding of how trastuzumab deruxtecan performs in the HER2-zero population, which have shown that this subgroup of patients does respond to the ADC, Graff notes. Therefore, this phase 2 trial will attempt to add to the understanding of how this approach could perform in an earlier line of therapy, Graff adds. This approach represents an investigation into another avenue for the use of trastuzumab deruxtecan, and it could ultimately represent an additional treatment option for another subset of patients, Graff says. This trial could lead to a better understanding how this agent hits HER2 and how much, if any, expression is needed, Graff concludes.