When, if ever, will you utilize T-DM1 in metastatic HER2+ breast cancer given trastuzumab deruxtecan's significantly improved efficacy vs T-DM1?

We now have very compelling data that trastuzumab deruxtecan (T-DXd) is highly effective in the second line setting and superior to T-DM1. The announcement of results came with the statement that "this study will lead to a paradigm shift in the treatment of Her2-positive metastatic breast cancer". S...

There may still be a role for T-DM1 in a patient who has been exposed to several regimens including all approved/NCCN-recommended regimens, or who may be intolerant or have contraindications to kinase inhibitors or to topoisomerase I inhibitors. However, 2nd and 3rd generation antibody-drug conjugat...

At this juncture, we do not know the efficacy of T-DM1 after T-DXd. I think for those patients who develop ILD or for whom, THP or T-DXd are too toxic or may have low volume metastatic disease, T-DM1 remains a good alternative. There are some single arm studies that have combined T-DM1 with HER2 TKI...

Later line - typically using THP 1st, trastuzumab deruxtecan 2nd line, cape/tras/tucatinib 3rd line...then I would consider drugs like T-DM1 at that point. We will have emerging data about mechanisms of resistance, but I think later line it is appropriate to try T-DM1 now.

I completely agree that TXD is more tempting given the data. However, I think T-DM1 still has a role as second line in the absence of myelotoxicity, neuropathy issues, absence of CNS disease, and slowly progressive disease/low disease burden. For now, using TXD as it is approved allows more treatmen...

Mechanisms of resistance to the ADCs have not been well defined. Some are likely to be resistant to the payload while others may be due to a change in receptor status with decreased delivery. Ongoing trials and RWE collection will provide some data on the benefit (a least ORR) with different sequenc...