‘Massive Improvement’ With Second-Line Enhertu in HER2+ Breast Cancer

The recently approved antibody-drug conjugate trastuzumab deruxtecan (T-DXd; Enhertu) was clearly more effective in treating metastatic HER2-positive breast cancer than standard-of-care trastuzumab emtansine (T-DM1; Kadcyla), researchers reported at the virtual European Society for Medical Oncology (ESMO) virtual meeting.

In this exclusive MedPage Today video, Amy Tiersten, MD, of Mount Sinai Hospital in New York City, offers her takeaways from the DESTINY-Breast03 trial.

Following is a transcript of her remarks:

The abstract that I’m most excited about is a phase III trial comparing two antibody-drug conjugates in HER2-positive metastatic breast cancer in the second-line setting. Prior to this study, an antibody-drug conjugate, T-DM1, was considered standard of care in the second-line setting, but this phase III randomized trial compared two antibody-drug conjugates in the second-line setting, T-DM1 and T-DXd, and showed a massive improvement in progression-free survival with the T-DXd molecule as compared to T-DM1.

The median progression-free survival was 25 months for T-DXd versus 7 months for T-DM1, which is a massive improvement that is one of the biggest differences I’ve ever seen in progression-free survival in any randomized trial.

What’s also interesting is that there was less interstitial lung disease seen in this clinical trial, probably because it’s a less heavily pretreated group of patients, because that was a major concern that had come out of the earlier T-DXd trials.

Certainly this will change my practice, and I will be using T-DXd in the second-line setting. I’m actually not so surprised about these results, because I have had such dramatic responses in my own patients and using T-DXd, but it’s really nice to see this important head-to-head comparison.