HER2 biomarker testing in practice | S14E1

Mm-hmm.

Yes.

And, and, and, and, you know, no HER2 testing is relevant in advanced non-small cell lung cancer.

We have, uh, uh, we currently have drugs approved for patients with advanced lung cancer who have HER2 mutations.

And also, uh, we has, uh, we, we, we have a, a, a approved, uh, trastuzumab deruxtecan on a tumor-agnostic basis for patients with HE- uh, 3+ overexpression, including those with lung cancer.

And we had the FDA approval, but recently we have also the EMA approval, no? So again, it's essential, uh, the work of the pathologists and the, the, you know, uh, the, the HER2 testing.

We need to, to perform NGS, uh, in all the patients with non-squamous histology.

HE- HER2 amplification is a mechanism of, uh, resistance in patients with EGFR mutations, and maybe also important to include, uh, patients in clinical trials as well as, uh, HER2, uh, overexpression, no? So, uh, I don't know, Fernando, if there is any different recommendation among different, uh, testing guidelines.

Perhaps we can review the recommendations, uh, in, in Europe, uh, about the HER2 testing.

Yes.

This, uh, I think is a, is a very, is very important, Enriqueta, because it can be sometimes a bit confusing because of, of all these different mechanisms.

I think most or all guidelines agree that we need to, um, to make sure that, that we test for HER2 mutations, uh, in patients with advanced non-small cell lung cancer, and the recommended method, uh, currently is, uh, next-generation sequencing because it's, it's very comprehensive.

And then you, you, you make sure that, uh, you don't miss any of these, uh, activating mutations.

And sometimes you do find copy number variation, uh, which traditionally, uh, this amplification has been studied by FISH, but currently it can be inferred from, from the results of next-generation sequencing, um, pipelines, particularly if you have enough tumor content.

And currently, as you were, um, saying, it, it's not clear how to deal with this, um, amplification, but it's mostly studied in the, in, in the settings, uh, of resistance.

So after treatment, uh, is, is one of the things that we can, um, identify and, and eventually, uh, treat with, with inclusion of, of these patients in, in clinical trials.

And so, uh, those are the two main, um, uh, considerations around mutations and amplifications.

And then, uh, to study HER2 overexpression, we need to perform HER2 immunohistochemistry, um, that it's, uh, recommended after, after progression.

And, um, and, and for that, we, we are going to be using, uh, HER2 immunohistochemistry.

And, um, and currently, we are following the, the gastric carcinoma scoring criteria because, as you also mentioned, um, now HER2 in, in lung has been developed as a pan-tumor biomarker.

So it probably makes sense to use, uh, a scoring criteria that is similar to the one that we've been using, uh, for our gastric carcinoma patients.

A-and, uh, Fernando, any role, uh, for liquid biopsy for, uh, HER2, uh, mutations or amplification?

Absolutely.

Uh, I think liquid biopsy is a, is a fantastic way of, of identifying particularly HER2 mutations.

Um, it's not that reliable to, um, estimate the, the, the copy number variation, but it can be done.