Thank you.

Thank you so much, and thank you to Neil Love and his team, and thank you, Jelena, for this introduction.

And indeed, we have seen a lot of progress in targeting her two positive G-junction or gastric adenocarcinomas, going from the single-lipidode monoclonal antibodies, trastuzumab, to antibody drug conjugate, to bispecific antibodies, and in gastric cancer, to a lesser extent, to small molecules.

And I will discuss in this short presentation some new data on the new drugs that are available and new strategies.

The first important progress after the data of trastuzumab were the data of Keynote 811, first-line treatment, chemo plus trastuzumab versus chemotrastuzumab plus pembrolizumab, which Yelena and others reported several years ago, showing a clear progression-free survival benefit, a clear survival benefit in patients with HER2-positive G-junction or gastric adenocarcinomas, and especially also patients with a PDL-positive tumor.

The subgroup analysis in this study in the PDL-positive tumor showed that there was a the benefit especially in this group there.

At this meeting, these are the data from the abstract.

Eric, since you were a little bit of an outlier, can you kind of review the data for us in that sense?

Eric, do you want to tackle

that one? Yeah, that's a good one.

That's a rare special case in this setting.

I don't think we have the data to make a strong statement which one we would go.

In Europe, we don't have the KRAS inhibitors approved, so we would go rather for a two-targeted therapy if they would be available, the KRAS-targeted therapies.

Yeah, intuitively, but that's just gut feelings.

That's no science.

But would you re-biopsy? Would you repeat a biopsy given the lower incidence?

Eric, is that something you do routinely?

Yeah, we try to recommend to do routine biopsies in the DESTINY studies, the DESTINY, at least the GASTRIC-02, DESTINY-GASTRIC-04 study.

This was mandatory.

The label doesn't say that you have to do it.

So we try to have a pragmatic attitude.

If possible, if easily, if you can take an easy biopsy, then I would do it.

If, of course, taking biopsies is very risky, then I would not do it.

I don't know, Eric, it's a European study, so

Is age just a number here, or would you approach this differently? Maybe Eric?

It's, of course, difficult without seeing the patient, but a 92-year-old patient, 93-year-old patient with an ECOG2, usually in our setting it's best supportive care.

It's for sure not chemotherapy in this setting.

In an in-depth discussion, if the patient really insists on HER2-targeted therapy, frontline could be an option.

The question is, of course, which one? Do we go for trastuzumab alone? Do we go for zanidatamab with a patient like that? Trastuzumab, Liruxtican, and ECOG2, 93-year-old patient, that's something I would not do in this setting.

Would you target HER2 or IDH2 in the second line? Okay.

Eric, you want to take that one? Well, the patient, as is indicated here, is HER2-IHC2+.

So the indication is you need a positive fish test after that.

Eric, is that something you do routinely?

Yeah, we try to recommend to do routine biopsies in the DESTINY studies.

The DESTINY, at least the Gastric O2, DESTINY Gastric O4 study, this was mandatory.

The label doesn't say that you have to do it regularly.

So we try to have a pragmatic attitude.

If possible, if easily, if you can take an easy biopsy, then I would do it.

If, of course, taking biopsies is very risky, then I would not do it.

Professor Van Kutsen, please take it away.