DESTINY-Breast04 ‘Practice Changing’ for HER2-Low Breast Cancer

Trastuzumab deruxtecan (Enhertu) demonstrated a statistically significant benefit in progression-free survival in patients with HER2-low metastatic breast cancer, meeting the primary endpoint of the phase III DESTINY-Breast04 trial. The results were presented at the American Society of Clinical Oncology (ASCO) annual meeting and published in the New England Journal of Medicine.

In this exclusive MedPage Today video, Aditya Bardia, MD, of Massachusetts General Hospital in Boston, explains why this trial will change the standard of care for this patient population.

Following is a transcript of his remarks:

The DESTINY-Breast04 trial was presented at ASCO in the plenary session and simultaneously published in the New England Journal of Medicine. The trial investigated trastuzumab deruxtecan or T-DXd versus standard chemotherapy for patients with metastatic breast cancer, who also had HER2 expression called HER2-low.

This is very important. Currently we define HER2-positive breast cancer as tumors that have a certain level of HER2 expression defined as IHC [immunohistochemistry] 3+ or FISH [fluorescence in situ hybridization]-amplified, but there’s also a subset of breast cancer that has some HER2 expression, IHC 1+/2+. Some call this HER2-low breast cancer. So this trial looked at the activity of T-DXd versus standard chemotherapy for this HER2-low metastatic breast cancer.

More than 500 patients were randomized to receive T-DXd versus standard chemotherapy. The trial predominantly had patients with hormone receptor-positive HER2-low breast cancer — about 88%. And then the rest were hormone receptor-negative HER2-low breast cancer.

In terms of the primary endpoint, the primary endpoint was progression-free survival. The trial met its primary endpoint, patients who received T-DXd had more than doubling of progression-free survival as compared to standard chemotherapy. Progression-free survival was also seen in the hormone receptor-negative metastatic breast cancer group, and was clearly seen in the hormone receptor-positive metastatic breast cancer group.

There was also improvement in overall survival with a hazard ratio that was clinically significant, and statistically significant as well. And this was seen again in hormone receptor-positive and hormone receptor-negative metastatic breast cancer. So these findings are remarkable to see such an improvement in progression-free survival, as well as overall survival.

In terms of side effects, the main side effect that was seen are side effects that we’ve seen with T-DXd, which include nausea [and] some degree of myelosuppression. A rare but known side effect of pneumonitis was also seen with T-DXd. The incidence was about 12% any grade, but the incidence of grade 5 pneumonitis was very low, about 1%, which is an improvement with what was seen previously with T-DXd in earlier studies and points to the importance of early recognition and management of side effects associated with T-DXd, including pneumonitis.

Overall in my mind, this is a practice-changing study. It’s a positive trial that changes how we treat metastatic breast cancer and is great news for patients as well as the field.

We are seeing increase in the interest of antibody-drug conjugates to treat patients with breast cancer. And it’s just wonderful to have this agent for our patients.