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HER2+ MBC: Integrating Newer Targeted Therapies Into Practice


Considerations regarding how to best integrate newer targeted therapies available for HER2-positive metastatic breast cancer [MBC] into clinical practice.

Ian E. Krop, MD, PhD: We have 4 new drugs, all of which are now approved, mostly in these patients who have had at least 2 lines of prior HER2-directed therapy. The question would be, how do you decide which one to use? For first-line and second-line therapy, we still use the tried-and-true standard of taxane, trastuzumab, pertuzumab in the first line, and T-DM1 [trastuzumab emtansine] in the second line. In the third line, we have these 4 new drugs. How do we decide which ones to use? I think different oncologists probably have different views. There’s no right answer here.

In my mind, it makes sense to use trastuzumab deruxtecan in patients who do not have brain metastases, or who had brain metastases treated a long time ago and never had another problem. The reason I think it makes the most sense to use that drug is because the efficacy of trastuzumab deruxtecan, which we really haven’t talked about yet, appears markedly more active than any of the other drugs we’ve had so far. The response rate in heavily pretreated patients is over 60%, and progression-free survival is approaching 20 months, which is roughly 3 times longer than what we’ve seen with other drugs in the pretreated setting. It works very effectively, very uniformly, and it tends to have very durable responses. I think it’s very nice to be able to tell a patient that you have a drug that’s going to work in the vast majority of people to some extent, and it’s going to likely work for a long time. One [adverse] effect of trastuzumab deruxtecan that we have to pay attention to is that in about 15% of people, you can get pneumonitis or interstitial lung disease, which can be serious and can be fatal in a small number of patients. That has to be monitored when you use that drug.

For patients who have significant brain metastases, using tucatinib-based therapy in the third line, to me, makes the most sense because the drug clearly shows activity in that setting. In the fourth line, you can switch to whichever one the patient didn’t get. After that, you can use this new drug margetuximab along with chemotherapy to take advantage of its immune effects. That’s in my mind how we integrate all of these new drugs, at least one approach for patients now that they’re all available.

Transcript edited for clarity.

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