DESTINY-Breast11: Clinically Relevant Adverse Events

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Welcome to DataPulse from San Antonio Breast Cancer Symposium 2025 on ReachMD. This activity, titled “DESTINY-Breast11: Clinically Relevant Adverse Events” is provided by Global Learning Collaborative.

Dr. Geyer: 
Hello from San Antonio Breast Cancer Symposium 2025 here in San Antonio, Texas. I'm Dr. Charles Geyer. Today I'd like to share some additional safety data that we heard during the meeting regarding the neoadjuvant study of incorporating T-DXd as a replacement for AC as neoadjuvant therapy for patients with high-risk HER2-positive breast cancer.

At ESMO 2025, we saw the impressive results on the primary endpoint of PCR that demonstrated across—irrespective of the hormone receptor status, we saw an absolute increase in the PCR rates in this high-risk patient population of 11% from 56% with the standard regimen of dose-dense AC followed by THP, versus 67% of 4 cycles of T-DXd replacing the AC followed by THP. So very impressive overall result.

We saw, of course, the usual split-out that in the ER-positive subset, the rates dropped slightly. The control group was at, I believe, 52% but it increased to 61% with the T-DXd. The really striking finding was it in the ER-negative patients, a population where many of the patients had presented with locally advanced disease, node-positive disease, the PCR rate went up to 83% with T-DXd, so very, very impressive in terms of the activity side.

The really interesting thing was that it was appearing from the top high-level cut of the data that the T-DXd was actually substantially less toxic than the anthracycline. We've used anthracyclines a long time. We have effective antiemetic therapy, and I think most of us have gotten comfortable with the medication and don't really view it as being that challenging to give anymore. Our big concern with it is cardiotoxicity that comes later. I had kind of felt like I could give AC, and patients seem to do pretty well with it. But when looking at this study, head-to-head with T-DXd, it looked like T-DXd actually seemed to be a bit better tolerated. And so what we saw here at San Antonio was really a much deeper dive, so to speak, into the information.

And what we did see, a little more granularity, we did indeed see that T-DXd was associated with more nausea and vomiting. Also might be associated with a little higher risk for neuropathy. But overall, when you got into the details of the adverse events, the T-DXd actually seemed to be well tolerated, except for the nausea and vomiting. And in the study, they really did not mandate antiemetic therapy. So we know that if you don't use antiemetic therapy with anthracyclines, you're going to have nausea and vomiting. So to me, the take-home from the data on the nausea and vomiting is use your aggressive 3-drug maybe even 4-drug combinations to manage that.

We also saw what I thought was very interesting finding, is that the ILD that was captured by the serial CT scans actually showed that there was as much ILD with the anthracycline as with the T-DXd, which is very surprising, because I don't think any of us really can recall many cases of ILD clinically in our patients that we've been treating with anthracyclines. But with those scans with blinded reading, there are changes that are occurring. So I think this is very interesting data about T-DXd and the ILD risk. With the 4 cycles of therapy there was half as much as we saw in DESTINY-Breast05.

So I think the results of the study clearly are consistent with DB05. Both of these studies are telling us this drug has a place in high-risk HER2-positive early breast cancer. It's going to help us cure more patients. I think we just have to figure out which patients need it and get better about mitigating the side effects to get the full benefits.

So from San Antonio Breast Cancer Symposium 2025, I'm Dr. Charles Geyer. Thank you for listening.

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Thank you for listening to this DataPulse from San Antonio Breast Cancer Symposium 2025 on ReachMD. This activity is provided by Global Learning Collaborative. Thank you for listening.