ESMO 2025 | Remaining questions surrounding the use of T-DXd in the curative-intent setting
Sara Tolaney, MD, MPH, Dana-Farber Cancer Institute, Boston, MA, discusses the use of trastuzumab deruxtecan (T-DXd) in the curative-intent setting, highlighting remaining questions such as the optimal duration of therapy and whether a shorter course could reduce toxicities while maintaining efficacy. Dr Tolaney also notes the uncertainty surrounding the timing of T-DXd administration, whether it should be given in the preoperative setting or after standard preoperative regimens, and emphasizes the need for further research to address these questions. This interview took place at the European Society for Medical Oncology (ESMO) 2025 Congress in Berlin, Germany.
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Transcript
So while the data from DESTINY-Breast05 are clearly practice changing and T-DXd should become standard of care for these high-risk residual breast cancer patients, there are a lot of remaining questions. One clear question is, do people really need all 14 doses of T-DXd? It’s a lot of therapy to get someone through. And to be honest, we have no real rationale for how we come up with these durations of therapy...
So while the data from DESTINY-Breast05 are clearly practice changing and T-DXd should become standard of care for these high-risk residual breast cancer patients, there are a lot of remaining questions. One clear question is, do people really need all 14 doses of T-DXd? It’s a lot of therapy to get someone through. And to be honest, we have no real rationale for how we come up with these durations of therapy. And it is giving people, in essence, chemo for about nine months. And so it’d be great to know if we could actually give shorter course therapy, significantly reduce toxicities for our patients, but maintain that efficacy. So I’d love to see more work done there. I think another major question is where should T-DXd actually be given? Because at this meeting, we also saw data from DESTINY-Breast11 looking at T-DXd in the preoperative setting where we saw pCR rates that were almost up to 70%. And so should you give the T-DXd up front when you meet a patient and give them neoadjuvant treatment with T-DXd followed by THP? Or should you give someone our standard preoperative regimens, either something like TCHP, or sometimes we use a de-escalated regimen of taxane, trastuzumab, pertuzumab. And then if they have residual disease, give them T-DXd based on what we’ve seen from DESTINY-Breast05. And so we don’t know the answer to this question. I think it is something we’re going to have to sort out. But it’s nice to have options because I think if someone came in with a really high-risk cancer and you’re trying to get them to pCR, then preoperative T-DXd could make sense. Whereas if someone came in with what you thought was a lower-risk cancer but ended up with a lot more residual disease than you’re anticipating, then you have T-DXd as an option. So again, these choices allow for a lot of flexibility and hopefully allow us to maintain outstanding outcomes for our patients.
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