Trastuzumab Derxutecan in HER2+ mBC


Sara Tolaney, MD, describes trastuzumab deruxtecan and the data that led to its accelerated approval in HER2+ breast cancer.


Sara Tolaney, MD: Trastuzumab deruxtecan [T-DXd] is a very novel antibody-drug conjugate that has a very potent payload being deruxtecan, which is a topoisomerase 1 inhibitor. It’s linked via a cleavable linker to a HER2 [human epidermal growth factor receptor 2] -directed monoclonal antibody. This agent is unique because it has a very high drug-antibody ratio. It has about 8 payloads per antibody, and it uniquely can function by bystander effect so that the payload that goes into the cancer cell can actually diffuse into the neighboring cancer cells and result in cell death. We saw very early on that this agent has very robust activity in the phase I setting, which led to a phase II trial. DESTINY-Breast01 had looked at trastuzumab deruxtecan as monotherapy in patients who had all been pretreated with T-DM1 [ado-trastuzumab emtansine]. What we saw was really pretty amazing results. An objective response rate that was a little over 60% with a disease control rate that was about 97%. Almost every single patient was having tumor reduction. Remember, this is a patient population that is heavily pretreated with a median of 6 prior lines of therapy. We’re seeing that not only is there this high response rate but actually that these responses are very durable. In fact, the median progression-free survival was over 19 months. Now very recently we’ve seen overall survival data that is almost 30 months. We’re seeing that this antibody-drug conjugate can have very robust activity even in heavily pretreated patients.

The data from DESTINY-Breast01 did lead to FDA [Food and Drug Administration]-approval of trastuzumab deruxtecan in patients who are getting treated in the third-line and beyond setting. These are patients who’ve all had, for example, prior taxane and trastuzumab, as well as prior T-DM1.

Transcript edited for clarity.

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