Komal Jhaveri, MD, FACP: One thing that I really wanted to talk about, not just therapies in this setting, but how do we test for these mutations? We spoke about ESR [estrogen signaling receptor] when we spoke about PI3K [mutations], AKT mutations, and HER2 mutations. How do we think about testing? Do you use tissue [or] do you use plasma, and why?

Gregory Vidal, MD, PhD: We’ve made the decision at my institution, very long ago, to have every first-line metastatic patient get a tissue profile. So, at our center, it’s a practice that we do. So yes, tissue upfront. Also important, for example, [is] in the hormone receptor-positive space. If that patient has been previously exposed to aromatase inhibitor and is currently on an aromatase inhibitor and doesn’t have an ESR1 mutation, it doesn’t mean that it couldn’t develop one in the future. You must do a liquid later because it may come on later. We know with exposure it can come on, and so, I do tissue upfront many times, and then repeat with a liquid on the back end because we can have new mutations that have interventions.

Komal Jhaveri, MD, FACP: Do you have a liquid assay that you use, or do you do something differently?

VK Gadi, MD, PhD: No. I was going to say the same thing. We want biopsies. We want tissue initially and as a framework for understanding what’s going on. Is the estrogen receptor still there? Those kinds of questions. But liquid, I’d like to say we’re an agnostic company. There are FDA-approved companion diagnostics for some of these tests, but they can get them packaged as a deal. You can get multiple biomarkers tested with some companies. So that might be an attractive option when you don’t have to rely on a single companion diagnostic. Not to speak to any one provider, there’s probably multiple options.

I was going to add to what you were saying, Greg, though we learned some data at this meeting showing that HER2, for example, is super flexible over time. Where you see patients really convert from zero to more and more low HER-ness. Not going to HER2-positive outright, but a little bit more HER expression, which then licenses patients to get a drug like trastuzumab deruxtecan [T-DXd] in the estrogen receptor-positive setting. So, plug not just for serial liquid biopsies, but there are patients where you might even still need to think about an actual needle going into a mass.

Transcript edited for clarity.

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