Fibroblast growth factor receptor

So, I mean, these are not common alterations that we see.

So FGFR, especially in advanced metastatic setting, I mean, I've had just a few handful of cases over the years, and the only FDA-approved drug right now in that space is erdafetanib, which is an FGFR-targeted therapy.

It's an oral drug, and it was approved based on a trial called THOR trial, which So this was a phase three randomized trial, and it had multiple cohorts in that study.

And it was a positive study.

So this is showing the variety of actionable or therapeutically targetable aberrations that have been found in biliary tract carcinoma.

A lot of these can be readily identified with NGS testing, such as your FGFR rearrangements, IDH1 mutation, and different biliary tracts arising at different portions along the biliary tree have different propensity for these types of aberrations.

Importantly, you'll note that some biliary tract cancers also show ERBB2 amplification, i.e. HER2 positivity.

And so HER2 targeted therapies, again, are an option for patients with biliary tract cancers.

So I think most of the studies have shown us that the decision globally from, um, investigators after failure to this first-line treatment is going into chemotherapy.

I think we also need to do testing in these patients, right? We all know the history about FGFR alterations, particularly targeted therapy with erdafitinib for those patient harboring this alteration.

So all our patients need, um, you know, molecular testing.

We also have this history, you know, for trastuzumab deruxtecan, so very important not only to get these next-generation sequencing, you know, studies, but also the immunohistochemistry for HER2.

So, you know, in my clinic, I still have some patients that, you know, over the time in further lines receive still chemotherapies as, you know, taxanes or others.

Well, uh, uh, Maite, you have mentioned a lot of new biomarkers.

Uh, but at the end, in the clinic, well, most of the times, we are only using two, uh, FGFR3 and HER2 right now.

Right now.

So we're sequencing the tumor.

So somebody with stage four bladder cancer that has no mutations versus somebody else that has, for example, a mutation called FGFR versus somebody else that has a mutation where they have HER2 ex- overexpression.

All three of those could potentially be treated differently.

So you can basically inhibit the flag or the FGFR that's on that person's bladder cancer.

This person that has HER2 overexpression, you wanna block the HER2.

And then this person that has neither, the standard treatment is the best thing for that patient.

And that's present in 10% to 15% of intrahepatic cholangios.

This is the third FGFR inhibitor approved for cholangiocarcinoma, and the fourth one that has some data.

I'll start with ertifetinib, which is one of the older FGFR inhibitors.

It's not FDA approved for cholangio.

It does have good data for bladder cancer.

It is a kind of a pan inhibitor of FGFR 1, 2, 3, and 4.

Pemigatinib is a reversible inhibitor of FGFR 1, 2, and 3.

Fudibatinib is an irreversible inhibitor of FGFR1, 2, 3, 4.