Sequencing HER2-Targeted Therapies in MBC

Ian E Krop, MD, PhD, elaborates on which treatment settings are most appropriate to use HER2-targeted therapies in to manage metastatic breast cancer.

Briana Contreras: I know some of these targeted approaches may be used at different times. You mentioned a few examples. In general, when should target approaches be used in the metastatic setting?

Ian E. Krop, MD, PhD: That’s a great question. I think unlike most other areas of breast cancer, in which sometimes we use target therapy, sometimes we use conventional therapies, in HER2-positive disease, it’s not really a question of when to use it. Because we’ve now shown in multiple studies that when you use a HER2-directed therapy, it’s always better than not using HER2 therapy. In every line of therapy we’ve looked at, using a HER2 therapy either by itself or with chemotherapy or endocrine therapy is always better than using the chemotherapy or endocrine therapy alone. In practice, what happens is, at least in the United States where fortunately these drugs are all available, we always have at least 1 HER2 therapy in everybody’s regimen. I think the data really support that. As we talked about, there are lots of different options, and how you sequence them can differ depending on patient preference and other factors. But I think the general sense is you should always have at least 1 HER2-directed therapy in your regimen, be it an antibody or a tyrosine kinase inhibitor, or a combination, or an antibody-drug conjugate.

Briana Contreras: Thank you. What are the considerations for deciding which targeted therapy is appropriate for a given patient?

Ian E. Krop, MD, PhD: I think that’s where things are evolving and where clearly a one-size-fits-all approach doesn’t make sense anymore. As I was talking about earlier, I think whether a patient has brain metastases at least helps me decide whether you’re going to use trastuzumab deruxtecan versus tucatinib-based therapy. We didn’t talk about neratinib, which also seems to have some effectiveness in the brain. My opinion about this is that we should probably use tucatinib in most of those patients first, along with capecitabine and trastuzumab, and then you could consider using neratinib after that if they have progression. But with the caveat that we really don’t have any data yet on whether neratinib does work after the use of another tyrosine kinase inhibitor like tucatinib. I’m hoping we get some data on that.

Those are the kind of things that we should think about, whether they have brain metastases. Somebody who has prior significant pneumonitis probably would like to avoid using trastuzumab deruxtecan, at least until you’ve tried other regimens. People who have problems with their GI [gastrointestinal] tract would like to avoid the drugs that cause significant diarrhea. I think those are things that should be considered. Some of these drugs cause less hair loss than others. For a patient who’s averse to hair loss, trying to use a regimen that doesn’t cause hair loss first would make sense. It’s definitely something where you have to consider lots of different variables. But it’s nice that we have all these different options.

Transcript edited for clarity.

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