Can’t fight DESTINY.

Headline: Trastuzumab deruxtecan is now positioned to be the go-to after failing chemo for metastatic HER2-low breast cancer.

The Study: To answer your first question, HER2-low was defined as 1+ per IHC or 2+ per PHC and FISH-negative. To answer your second question, trastuzumab deruxtecan (TD) is the anti-HER2 monoclonal antibody we all know and love conjugated to a topoisomerase I inhibitor. The DESTINY-Breast03 trial has already proven the role of TD for metastatic HER2+ breast cancer. Yesterday’s ASCO plenary session has brought us the next iteration, DESTINY-Breast04 that, interestingly, now establishes  the role of TD in the aforementioned HER2-low population. Across 557 women randomized 2:1 to TD versus physician’s choice chemo, the primary endpoint of progression-free survival was doubled after TD from 5 → 10 months. What’s more, even overall survival was improved from 17 → >23 months. And all of this came with less grade 3+ toxicity than with chemo.

TBL: Trastuzumab deruxtecan significantly improves outcomes for women with metastatic breast cancer with any degree of HER2-IHC staining. | Modi, N Engl J Med 2022