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What’s Making the Impossible Possible in Pancreatic Cancer?
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Released: January 02, 2025

Expiration: January 01, 2026

John Marshall
John Marshall, MD
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What’s Making the Impossible Possible in Pancreatic Cancer?

John Marshall, MD: This is John Marshall for Oncology Unscripted, and we're going to talk a lot about pancreatic cancer today.

Our main topic today is really all-around pancreatic cancer. We just got out of November. And as you know, November is Pancreatic Cancer Awareness Month. Now, did you know that there are about 60, 000 new cases of pancreatic cancer every year? Not that many survivors, right? Because most patients present with metastatic disease, and is there such a thing as early pancreatic cancer? And so, the teams that have been trying to advocate for new science in pancreatic cancer have made headway. First, you need a month. So, they got November 2nd. You need a ribbon. Do you know what color the ribbon is? Yep. Yep. You're right. It is a purple ribbon. So you got to have a ribbon. You have got to have a month. Got to have a few five K's. You have got to have some money. to distribute out there for research and you've got to create a home for patients to go to, so that they can learn more about their disease. And so Pancreatic Cancer Awareness Month has really been something that I would say has been positive for our patients and our medical team in this space.

I want focus on a paper actually that came out last month in the JCO, and this paper by Ludmir et al, was kind of breaking a rule, but it worked.

Now, you remember that in colon cancer, not pancreas, colon cancer, you can resect metastatic disease. In fact, you should for some patients because sometimes there's only one or two weeds in the yard. And if you remove the metastatic disease, you cure that patient. But generally. We don't do that for other cancers routinely, but this group published their data looking at pancreatic cancer patients with five or fewer lesions, metastatic lesions, randomizing them between just continuing chemotherapy versus this metastectomy or localized treatment, and wouldn't you know it, it seemed to work. So, the next time you're in your GI multidisciplinary tumor board, and somebody, some surgeon usually says, what if we just took those mets out of the liver? And that you would use to say, nah, it's pancreas cancer. There's no data. Now, there is data. So, I strongly encourage you to look up that paper, maybe present it at your next multidisciplinary tumor board so that you too can be cutting edge, if you will, on trying to do a better job with pancreatic cancer.

Now, the other piece that happened in November is we have our annual Ruesch Center Symposium here at Georgetown. We invited people from all over the country to come and start off with a think tank. What do we know? What don't we know? Actually, we know a lot more than we used to know. We then celebrate this with a series of presentations and a CME symposium. And I wanted to sort of really drill down on pancreas cancer for a little bit, because we've made progress, believe it or not.

So, it really starts with an understanding of there is such a thing as early phase pancreatic cancer premalignant lesions within the pancreas. There's increasing ability to detect these things. Now, how do we prevent them from becoming a cancer? That's another challenge. How do we identify them as a screening tool? There's new data that supports being able to do some of these new screens,  both with blood testing, as well as with imaging, et cetera. So, there is hope that soon we will be able to incorporate routine screening in patients to try and find early-stage pancreatic cancer, even premalignant.

The second, and this is a big deal, is we have been saying that RAS is untargetable. 90 percent of pancreatic cancers have a RAS mutation. And we basically said, we're sorry, your driving mutation is untargetable until now. It started with G12C and now there are, gosh, some people say more than 20 new drugs that are targeting RAS, increasingly more successful. Some are very specific to a certain mutation. Others are pan RAS inhibitors, but there are a lot of clinical trials, a lot of new therapies, and a lot of investment that's going into this space of targeting RAS in pancreatic cancer. And our hope is that Maybe even by this time next year, we have some positive randomized data that would lead to FDA approvals.

My guess is between now and then, we will also be seeing some phase 2 data that suggests significant positive responses. All of a sudden, we're seeing waterfall plots with pancreatic cancer, not with just one patient, 10 percent, having a response, but now approaching 50 percent of patients having response. And I am really excited about RAS inhibition in pancreatic cancer now.

The last piece of this is that you think of pancreatic cancer as sort of an immune silent disease. disease that there's no treatment for therapy, no role for immune therapy in these patients. But newer studies looking at novel combinations of immune therapies are starting to show some improvement in waterfall plots as well.

So, when we got everybody together here at our symposium and our think tank, what really came out of it is that It's now on us to figure out how to put together these immunotherapy approaches and these RAS targeted agents along with our existing systemic agents to move the bar in pancreatic cancer.

Is it about time? Yes, it is. Do we have the right drugs? We at least have a good wave of drugs That will move us forward in this space. So, if you're out there taking care of patients like me with pancreatic cancer, now's the time to be looking out for trials and other options as these agents come through the mix. Hopefully, this time next year we have improved survival and a path forward about how to make that even better. So, I'm optimistic around pancreatic cancer.

To really get into this area of pancreatic cancer, we've invited not only a good friend, but someone who I think maybe single handedly has had more impact on the outcomes, the investment, the support for pancreatic cancer. There's no one out there on the planet, in my opinion, except this person, Julie Fleshman, who started, founded, grown, this organization the Pancreatic Cancer Action Network. [00:11:20]

This transcript has been lightly edited for clarity.