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DESTINY-Breast04 'Practice Changing' for HER2-Low Breast Cancer

— Trastuzumab deruxtecan shows remarkable improvement in progression-free and overall survival

Ƶ MedicalToday

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 and published in the .

In this exclusive Ƶ video, , 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.

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    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams.