ESMO 2025 | T-DXd vs T-DM1 in high-risk HER2+ breast cancer: DESTINY-Breast05 interim data

I think the findings from Destiny breast cancer 05 that we saw at ESMO this year are practice-changing. To me, there were some of the most exciting data that we saw at ESMO because it focused on a very high-risk group of HER2-positive breast cancer patients. So these were patients who had residual node-positive disease after getting neoadjuvant therapy or came in and presented with a tumor that was inoperable at baseline and then went on to have residual cancer. And they randomized them to get T-DXd for 14 cycles or T-DM1. And they found that those patients who received T-DXd actually had a much better outcome. It reduced their risk of recurrence by half when compared to T-DM1. It was an absolute difference of about 9%. And so to me, this is quite profound because the majority of events that we saw were actually distant recurrences and it reduced distant recurrences by half. One interesting little tidbit was we were kind of curious to see if T-DXd could actually prevent CNS relapse, because in the original Katherine trial that had looked at the use of adjuvant T-DM1, we saw no reduction in risk of CNS relapse. In this trial, Destiny breast cancer 05, we saw that T-DXd did have a numerical improvement in terms of CNS events, so there were eight fewer CNS relapses in the T-DXd arm compared to T-DM1. It’s early on, the median follow-up time is only about 30 months. So I do think we need to follow this out longer to see if this is a real signal, but I think it’s very, you know, a strong indication that maybe T-DXd can do better than T-DM1 even in the CNS. So I think it’s exciting to see that.

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