Trial argues strongly for the development of 1st-line biomarker selected strategies in pancreatic ductal adenocarcinoma

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Published: 4 Jun 2024
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Prof Jennifer Knox - University of Toronto, Toronto, Canada

Prof Jennifer Knox speaks to ecancer at ASCO 2024 about early results of the PASS-01 trial, which evaluates the benefit of 1st line modified FOLFIRINOX versus gemcitabine/nab-paclitaxel in de novo metastatic pancreatic ductal adenocarcinoma (PDAC) patients.

She explains that the idea behind the trial was to understand whether there are any biomarkers that can be identified early on in the diagnosis of metastatic pancreas cancer and use this to inform treatment after standard-of-care chemotherapy.

Prof Knox reports that very little difference was seen between the chemotherapy regimens and the unimpressive performance of both highlights the importance of precision treatment and adding novel therapies into the mix.

Trial argues strongly for the development of 1st-line biomarker selected strategies in pancreatic ductal adenocarcinoma

Prof Jennifer Knox - University of Toronto, Toronto, Canada

The PASS-01 trial, PASS stands for Pancreatic Adenocarcinoma Signature Stratification for Treatment. What we’re trying to do is try to understand are there any genomic, RNA or other biomarkers that we can pull out very early in the diagnosis of metastatic pancreas cancer and use it to inform treatment for these patients after the standard of care chemotherapy? And maybe even more importantly learn from that who responds better to what type of chemotherapy so that we can improve the selection up front for patients going forward. So that’s the trial we’re presenting.

What are the results?

It’s interesting, when we started the trial we made the assumption that while both chemotherapies that we have today, FOLFIRINOX and gemcitabine/nab paclitaxel, are very useful, the assumption was that FOLFIRINOX would be a little better. So we powered it assuming that we would see a slightly longer signal for FOLFIRINIX than the gemcitabine/nab paclitaxel but we would learn how to use each one of them perhaps better.

What is a little surprising is that that’s not what we showed. We showed that there is essentially very little difference between either of those chemotherapies and, in fact, the gemcitabine/nab paclitaxel came out as a little bit ahead, a little bit longer time for the patients to progress and a little less toxicity. Now, having said that, I don’t really think either of them are great, they both leave much for improvement, but it opens the discussion that we shouldn’t be hanging our hat on one of the other, we really should be trying to choose from the beginning what will be best for this patient and then building on that.

What could be the impact of this research?

It will be interesting to see how this impacts clinic. I hope this gives oncologists a little bit more comfort knowing that it isn’t wrong to choose one or the other and if there is a trial that is using one of these for good scientific reason then that makes sense. But to avoid one or the other without a scientific rationale doesn’t make any sense.

What we’re hoping is that, as the data matures a little bit, we’ll be able to strongly say you can pick certain subtypes of pancreas cancer right from the beginning. There’s something called the classical, there’s something called the basal, and this you can tell in the RNA signatures. Right from the beginning you know this one will probably be doing better on gemcitabine/nab paclitaxel, let’s add a KRAS inhibitor, let’s do something innovative on top of that rather than just waiting for a subsequent line.

One of the other findings in the PASS trial is although we’ve done all this intensive science on every patient, the reality is that only just over 50-60% ever get a chance to even use that and move to second line because they deteriorate so quickly. So moving all that information up front and using it earlier on is likely to impact patients a lot more.

Anything else you would like to add?

We’re moving into a very interesting time. I don’t mean to say that I don’t think chemotherapy has had its role; it’s been very helpful, especially these combinations, but we have to use them smarter. We have to know who is going to respond to one and not to the other and then we have to start adding novel targeted agents, KRAS inhibitors, different things like that, to the chemotherapy and optimising each patient so we’re not getting 60% getting to second line, we’re getting 100% to second line and then they’re doing well as well. So we’re moving into good times for pancreas cancer and the past data will be very informative to try to build those next steps.