ESMO 2025 | Expanding the use of T-DXd in intermediate-risk breast cancer
Charles Geyer, MD, University of Pittsburgh Medical Center, Pittsburgh, PA, highlights the potential use of trastuzumab deruxtecan (T-DXd) in intermediate-risk patients with breast cancer, highlighting the need to clarify recoverability and reversibility before considering its application in lower-risk populations. Trial data has justified the use of T-DXd in the existing patient population, with a significant reduction in recurrence rates, but further analysis is needed to determine the optimal dosing and patient selection. This interview took place at the European Society for Medical Oncology (ESMO) 2025 Congress in Berlin, Germany.
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Transcript
So technically, we don’t have a lot of very insightful studies on sequencing. If you take, for instance, PSMA lutetium, you know that giving it before or after the taxol doesn’t make a big difference. If you look at PSMA Vision and PSMA 4, it’s roughly the same response rate and PSMA 4 tells you you can delay a little bit. For radium-223, what we know is that it shouldn’t be given too late, otherwise it doesn’t work...
So technically, we don’t have a lot of very insightful studies on sequencing. If you take, for instance, PSMA lutetium, you know that giving it before or after the taxol doesn’t make a big difference. If you look at PSMA Vision and PSMA 4, it’s roughly the same response rate and PSMA 4 tells you you can delay a little bit. For radium-223, what we know is that it shouldn’t be given too late, otherwise it doesn’t work. In terms of sequencing, the only certainty we have is that as soon as possible, this patient should be tested for DNA repair and the PARP inhibitor should be fed in as soon as possible, probably even in the metastatic or more naive setting. So that we know. For the rest, you have three drugs, radium, PSMA ligand, two chemotherapies. So the best strategy is the strategy you manage to give everything to everybody so I would recommend giving it very early when the patient has a time to monitor PSMA expression on a regular basis because if your patient has a very high PSMA expression that’s the time to give PSMA therapy and feed in docetaxel early. There was a beautiful trial from Kim Chi, Vancouver, Canada, comparing docetaxel to PSMA lutetium and actually showing that if you start with docetaxel first, you have a benefit in overall survival. So that’s a very strong message in terms of sequencing.
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