How do differences in toxicity profile factor into your choice between a T-DXd-based neoadjuvant regimen and ddAC-THP?

I have largely abandoned AC in HER2-positive EBC. Cardiac toxicity is just as unpredictable as ILD, in my opinion, and when it occurs is irreversible. There is also the issue of treatment-refractory MDS/AML with anthracyclines.

The standard-of-care arm does not reflect my typical practice for this patient population. I almost always treat with neoadjuvant TCHP, so patients are usually spared anthracyclines. That being said, the real risk of ILD requires that we appropriately select the patients who receive T-DXd-THP. Speci...

While the DESTINY-Breast11 trial ( >T3, or N+ or inflammatory breast, although the FDA approval includes T2N0) compared T-DXd-THP vs. ddAC-THP, the non-anthracycline TCHP has comparable path CR rates to ddAC-THP with less risk of cardiotoxicity, secondary malignancies, febrile neutropenia, and simil...

We don’t really do a lot of ddAC-THP anyway, so we have moved away from it to avoid excess cardiac toxicity relative to non-anthracycline regimens.