FOLFIRINOX

You don't sound impressed by that.

Well, that's Folfirinox by another name, isn't it? It is, yeah.

That's quite punchy, isn't it?

Yeah.

And once it has metastasized, survival is lowest of all.

Even the strongest standard chemotherapy combination, FOLFIRINOX, extended median survival to about eleven months in the landmark trial published in the New England Journal of Medicine.

Eleven months, and that was the good result.

So families facing metastatic pancreatic cancer feel time differently.

What can we add to that? And keep in mind that 5-FU had similar outcomes, that we have activity with 5-FU for these patients.

You'll see that as a- another part of a backbone when we think about our modern treatment algorithm with gemcitabine plus capecitabine and with the modified FOLFIRINOX regimen, wh- which we will discuss here shortly.

All this was a lot.

Check out our show notes for more details on this, particularly for this historical interlude.

But remember, gemcitabine monotherapy was the backbone.

So can one of you get into how did we get to this combination therapy when we think about gemcitabine plus capecitabine and this modified FOLFIRINOX?

And a lot of this builds on the work that Vivek just outlined.

Gemcitabine really was that standard of care, but of course, we're always trying to push that envelope and see what can be better.

We gave them four months of the platinum-based therapy.

Did you know in the clinical trial that brought that to market, they didn't get much more?" This is FOLFIRINOX, that's 5-FU, irinotecan and the platinum, that's the platinum-based therapy, versus gemcitabine, the older drug in pancreas cancer.

It's an older paper in New England Journal.

And in the paper it says this: The median number of cycles administered was 10 in the platinum group and 6 in the other group.

But POLO was a study that only enrolled you if you didn't progress in the first four months.

So how many people in this study progressed in the first four months? And the answer is about a third.

A third of them progressed on FOLFIRINOX in the first four months.

So that average of five months of treatment or 10 cycles is in everybody.

Zalbetuximab was the first in class at Claudin 18.2-directed monoclonal antibody.

It was evaluated in two global clinical trials, SPOTLIGHT and GLOW, and each of those used a different chemotherapy backbone respectively, although both were oxaliplatin and FOLFIRINOX.

The SPOTLIGHT trial evaluated FOLFOX plus or minus zalbetuximab, and the GLOW trial evaluated CAPOX plus or minus zalbetuximab.

For entry into both clinical trials, patients were required to express Claudin 18.2 at IHC two or three plus on more than seventy-five percent of cells, so that is our cutoff for Claudin positivity for zalbetuximab.