Main Topic: Dr. Marshall confronts the chaos unfolding in Washington DC, where sweeping federal cuts are threatening the very foundations of cancer research and care. Taking us on a journey through some of the life-saving and groundbreaking innovations that all began with federally funded science along with the recent progress in one of the historically toughest cancers—pancreatic cancer. Dr. Marshall asks: How do we fight the dismantling of this important system and protect progress? Interview: In this Candid Conversations episode, Dr. Marshall revisits his conversation with Julie Fleshman, President and CEO of the Pancreatic Cancer Action Network. Julie shares the personal story that sparked her advocacy, the evolution of PanCan, the organization’s pivotal role in driving pancreatic cancer research, patient support, and clinical innovation, reflecting on the progress made for one of the most difficult-to-treat cancers. MedBuzz: Dr. Marshall’s call to action regarding the sweeping federal cuts to key health and research institutions, including the NCI, NIH, and FDA. With sudden firings, hiring freezes, and growing instability in the cancer research ecosystem, he issues a passionate call to the oncology community: speak up, stand together, and push back before decades of progress are undone.
We Funded the Cure—Now We're Pulling the Plug?
John Marshall: Welcome to Washington DC. My name is John Marshall. This is Oncology Unscripted. There is a whole lot of stuff going on out there, seemingly unscripted, seemingly without much in the way of a sense of motivation, really a plan. It's just blow it up. Let's see what'll happen after the fact.
But let's stop for just a second and think about what science, federally funded science, has accomplished over the last many decades here. Because a lot of us, including a lot of the population as well as the government, feels like, it was really business that did everything, not the government. So, we should shift all of this money over to business and take it away from the government. So, they're firing all sorts of people here in Washington and around the country with the science community.
But let's start by acknowledging what science has done for our health. So first, we know that cancer mortality has fallen dramatically. If you think about when I first started as a fellow a thousand years ago, really the only investment in clinical translational research was through the National Cancer Institute, occasional company here and there, and all of this improvement that we're seeing today comes really from that beginning, and so we've had a clear, positive influence. But let's look at some of the details here. The concept of, I don't know, rituximab, immunotherapy, and multi chemotherapy treatments, and the cures for lymphomas comes out of government invested research, bone marrow transplant comes out of government investment research.
How about understanding HPV and using vaccines? I know. Vaccines are crazy things that we shouldn't be giving because they're terrible things, right? According to the current government. But let's talk about the discovery of HPV and vaccines, which is going to get rid of HPV-mediated tumors.
What about imatinib? Remember that drug that was really out of the beginnings, of government research? But you know what? One of the ones that's my favorite is actually HER2. HER2 was discovered with government funded research, the therapies for treating HER2-targeting, transforming it from just a bad target, prognostically bad target, to something that actually is good news nowadays because we know how to treat it well. That was all done with government research, right? And so then here comes swooping in a pharmaceutical company under the name of Genentech that took it and made it into a billion-dollar profit that helped to fund other research.
And so, we have failed to value the innovation that comes from the government world, and there's just so much of it out there. And over the last month or so, there's been this dramatic downsizing of grants, grant applications, payment for grants that are funded, downsizing the number of people who are at the National Cancer Institute and other places around the world where there is federal funding for these with the, with the idea being that that's just wasteful, I guess that's the thought.
We know that the NIH investment has fueled a great deal of economy in all of the places that it's ongoing. So, not only is it producing science and our understanding of the biology of cancer and other diseases, it is also helping the local economy. Then what really got me going on, this was an ad. I'm pretty sure you're probably seeing them too, at your home for our new president and our new, folks that have taken over, ruling our country in a completely different way. And in fact, this team had the boldness to put out an advertisement that in four years they will cure cancer. You should watch it. It's just unbelievable. If they're going to fire all of these people who are the brains and the brain trust and the innovators and they're not going to fund the science that's teaching us what we need to know in order to actually cure cancer. We're going to get rid of all of those people and somehow through some other mechanism, they are going to have cured cancer in four years. So, what have we got to worry about? Right? This is going to be all fine because don't you worry our boss is going to cure cancer.
Speaking of cancer that we need to cure. We've been talking a lot lately about pancreatic cancer and what a difficult disease it is, and despite great deal of investment and positive input around it, we've made some strides, but not the kind of strides we need to make. But I do want to reinforce the progress that we have made. I've been thinking a lot about pancreas cancer comparing to colon cancer. I'm still giving the same adjuvant therapy I've been giving in colon cancer for 21 years. That's an embarrassing statement. On pancreas cancer, we have made progress. We know the drugs that are working there better. We are curing more people with pancreas cancer. One of those innovations is liposomal irinotecan, and the idea that you could take existing drugs and improve their performance by modifying their delivery and the formulation, and that's what liposomal irinotecan is all about. So, we now have pretty clean data that frontline incorporation of liposomal irinotecan in a FOLFIRINOX recipe is in fact better than other options in frontline.
And so, it really begins to fall on us more and more to make individual decisions about which drugs we're going to use and when. And so, this pushes down onto each of us. A sort of plan or a strategy of what regimen do you give in frontline? What do you give in second line? Which of the drugs do you combine? I think the best data we have is with NALIRIFOX, if you will, in frontline.
How much of this is going to be under our control? We are all feeling the pressure. How many peer-to-peer reviews are you having to do every week for what is essentially standard of care? I'm doing too many of them I have to tell you. So, we are clearly feeling an outside pressure in healthcare today about incorporating what we see as best of care for our patients, and so I want us to make sure that we are connecting, that the experts in your area and the generalists in your area are talking. And that we're sharing advice and optimizing individual patient care for all patients throughout our communities, because we know that if you do that, you get better outcomes. It's not necessarily about being more aggressive. That's often the term we use. It's honestly about being more effective.
As you know, we've been interviewing some of the leaders in the world of pancreatic cancer and we thought it would be appropriate to reshow some of these key comments that leaders have made, such as Julie Fleshman, who started and runs the biggest advocacy group for pancreas cancer, PanCan.
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Pancreatic Progress: Revisiting our Discussion with PanCan CEO Julie Fleshman
John Marshall, MD: Welcome everybody back to Oncology Unscripted. No script at all on this one and the person who's joining me right now, really, doesn't need a script because she wrote it. She was the one who really defined, in my opinion, what advocacy is all about. Taking maybe one of the most difficult, if not the most difficult, cancer, inspired by a personal story to change the outcome for people with pancreatic cancer. And I'm proud to say she's my friend, but she's also one of my mentors, as she has shown the way for so many as to how to really move the bar in advocacy. And this is Julie Fleshman, who is coming to us live and we're so grateful, Julie, for your joining us. So, first, welcome to Oncology Unscripted.
Julie Fleshman: Thank you so much for having me.
John Marshall, MD: You are so awesome. And you know, I think that, but let me start from the beginning, because a lot of people were coming up on a change in our world. And we know that advocacy is a critical component to our success in making advances in healthcare. It's not just handed to us. We have to push the forces around us to make it happen. Maybe give us your Quick version of, you know, what inspired you and the value of advocacy in the world of pancreatic cancer.
Julie Fleshman: I have a personal story. 25 years ago now, my dad was diagnosed with pancreatic cancer. 52 years old. Died four months after diagnosis. And I was devastated, and I didn't understand why there was nothing offered for him. Why were there no options? At the same time PanCan was founded and I was lucky and privileged to be hired as the first employee almost 25 years ago.
And I've really just watched, you know, the field, the pancreatic cancer field back then, there was nothing. There was no federal funding. There was no philanthropy. There were no, there's nobody studying the disease. There were no resources for patients and families. And you know, I really believe PanCan has been a catalyst for changing that. And today there is a robust pancreatic cancer research community. And I think a lot of exciting things on the horizon for patients. And so, you know, I believe advocacy being the voice of the patient, not backing down when everyone tells you this isn't the way that we get things done, but it makes the most logical sense for overcoming a hard disease and you keep at it and you keep chipping at it. And I believe advocacy is what gets us to where we're going and accelerates the rate of progress. And in this case, I think it has really helped to build a field that just didn't exist before.
John Marshall, MD: You did all that stuff. Let's talk about the important stuff. Why did you pick purple for the ribbon?
Julie Fleshman: So actually, our founder who lost her mom to pancreatic cancer, her mom's favorite color was purple. That is the story.
John Marshall, MD: I love, I love that.
Julie Fleshman: So yes, so you know, and it was one of the colors not taken, right? You can't, you need to have something different than the other cancers, but it is a great color.
John Marshall, MD: But all kidding aside, yeah, I actually have several purple ties now because of the of the purple ribbon. But all kidding aside, I mean, you have you and your team have built an incredible infrastructure, not just a Hill presence and an advocacy there. Not only a clinical research infrastructure that we'll talk about in a minute, but also operators standing by patients can call in, and get advice about what they should do with your team members. And in fact, I think that feeds back to the practicing clinician, because there's a lot that we don't know that's going on out there, particularly the general oncologist in the world of pancreatic cancer. I'm assuming each one of those was a decision and you needed to have the bandwidth to do it. Like how, how much struggle was that to get all of those resources together?
Julie Fleshman: Yeah, I mean, you looked at and said, okay, where are the gaps, and 25 years ago, there were a lot of gaps. One of the first and most obvious areas was, you know, when someone is diagnosed with this disease, there's no place to go for information or resources. So building that patient services program in the early days, you know, was so critically, I believe, important for helping patients be informed so that they can make the right decisions about their care and go in and be an advocate with their, you know, doctor. Just as you said, many physicians don't see hardly any pancreatic cancer patients. And so, to have someone come in and ask you questions about clinical trials, about testing, about these different things, and hopefully it is also helping to educate the health care professionals.
John Marshall, MD: Yeah. And you've given these folks a home, a club, if you will, where they can share thoughts. And I think with our, you know, the bad cancers, there isn't that sort of survivorship that you see in some other cancers. So you've, you've provided that place where people can interact and teach each other, which to me is just critical.
Julie Fleshman: Everybody needs a cheerleader, right? Whether you're a researcher, a doctor focusing on this tough disease, patients and family, someone who's lost someone. And I think that's what PanCan does. We rally the troops. We make people feel good about the work that they're doing and that there is hope and that we're going to get there. We just all have to work together to do it.
John Marshall, MD: Let me, let me kind of drill down on something you and your team were clearly setting those standards when you develop the concept around precision promise. This was an understanding that molecular abnormalities occur. There are different ones in different patients. We have targeted therapies. Could we drive progress in pancreatic cancer through that? And you, a lot of work, a lot of investment, a lot of science went into this, but it didn't turn out the way you want to maybe reflect a little bit about that and that experience for others, because, you know, for me personally, I think it's exactly the right way to go. And lessons we could share for others trying to do this and other diseases.
Julie Fleshman: Yeah. Yeah. So Precision Promise was an adaptive clinical trial platform. And so, you know, basically the goal behind it was that you could develop a drug with fewer patients, less cost, less time, a way to accelerate new treatments for patients. All of that's true. And I think we learned a lot about sort of that process, and does this platform concept work? And I think the answer is yes. However, in order to make it financially work, you have to constantly have new drugs coming into the pipeline on the platform. And that was the part that turned out to be the, the challenge. Part of that was, you know you were convincing a pharmaceutical company or a biotech company to develop their drug, that PanCan was going to develop their drug, they were going to lose control. So that proved to be an obstacle. The pharma and biotech companies, you know, changed their priorities and their strategies. And so maybe at one point they were developing this drug in pancreatic cancer and six months later they were deprioritizing the asset. And so all of those things became challenging.
The trial will go on. another organization that is going to launch a new, you know, basically Precision Promise version 2.0 and learn from all the things that that PanCan learned over the last, you know, four years. And, you know, Some people have said it was before its time, you know, now with there's so much excitement around drug development and targeting KRAS and all of these things that maybe, you know, if we were launching it today, it would be a different story. We launched it in 2020 in the middle of COVID. It was, you know, couldn't have been a worse time to be launching a, a big, you know, basically phase three clinical trial for an organization like us that had never operated one before. So, you know, we, we didn't have all everything working with us, we did this, but we certainly learned a lot.
And I think, you know, the, the investigators that were a part of the network and the sites that were running Precision Promise, really, that part ended up being pretty amazing. That network, and the camaraderie and the sharing and the learnings. and you know, I think that those things will continue far beyond.
John Marshall, MD: Yeah, no, I totally agree with you. You know, we, held here at Georgetown at the Ruesh Center, a think tank around pancreatic cancer. And we, we invited a bunch of very smart people. some of the smartest people in our country around this disease who've made a lot of progress. And the whole point of the think tank was to say, why haven't we cracked this nut? Why have we had a few new medicines? They've helped. Yeah. But we really haven't cracked the nut the way we want to. And it was interesting. One of the participants got up and said, but wait, we have done it or we have about to do it and all we really need to do is give it time and ongoing investment. But we're about to reap these rewards in pancreatic cancer, whether it's targeting or new understanding of immune therapies, understanding, how to control. cancers and the like I went into that meeting discouraged thinking there wasn't going to be much in our summary document of what we were going to be able to share, but I left that meeting maybe as excited as I've ever been, and I'm an old GI oncologist, as excited as ever been about the future of where we're going in pancreatic cancer reflect a bit where you all are on that and that stance and The one concern I had again is how do we make sure that that investments there to your previous point? How do we make sure that patients have access to these trials and new medicines around the country? So that all can move this faster. What are your what are your thoughts on that?
Julie Fleshman: I've heard multiple physicians and researchers say that they feel we're at a tipping point, and I've never heard, you know, that kind of talk, before. I mean, 25 years, I've been told KRAS, RAS and KRAS, super important. but it's undruggable. And suddenly, it's druggable. And so that's pretty amazing and exciting. you know, there are multiple, multiple companies with targets for KRAS for pancreatic cancer. The first phase three trial just launched last month. and then lots of phase two, phase one trials that are in development. So, I mean, this is exciting. This is really important.
John Marshall, MD: Yeah, I was going to say that we saw I saw a bunch of waterfall plots. Everybody knows what those are, where I'm used to seeing one patient and being excited about that. This was half the patients were below the line. We were seeing lots of, responders in those patients.
Julie Fleshman: Absolutely. And, and most likely it won't be the silver bullet. I think we've learned that in this disease. So the next step is what do we need to combine it with? What is that going to look like so there's durability, and, and we get, you know, even we extend patients lives even longer. I think that'll be the sort of immediate next step that we need to begin working on. But I was really heartened, at the AACR pancreatic cancer meeting That already it feels like the field is thinking about that, and they're working together across institutions. They're getting together in groups and trying to solve the problem based on different expertise. And so, I do feel like we have a very special community that knows this is hard. That this isn't just going to be the answer, and we're going to have to continue to work together. And PanCan wants to play that role. Whether we're funding, advocating, educating, you know, whatever that looks like to ensure this moves, moves forward for.
John Marshall, MD: I would go one step further, Julie. I don't think we would be where we are today with that progress without your work and PanCan's work, and we are all looking forward to the future in large part, thanks to you. So, I very much thank you for taking the time to talk with us today and, and wish you well as now we watch that survival curve improve.
Julie Fleshman: Thank you so much. I always appreciate your passion and enthusiasm, and, and all you do for patients. So, thank you.
MedBuzz: Who’s Next? Cancer Research in the Crosshairs
John Marshall, MD: If your world is like mine, you're spending a lot of time thinking each day about the impact of governmental changes, administration changes, and their impact on us as healthcare providers, us as humans. Us as educators, us as researchers in the world of cancer care today, and we know there are dramatic events occurring every day that we are sort of figuring out what's the impact, how do we preserve what it is we wanna do?
So, for example, as little as one week ago. Some of the fellows that matched in our area here in Washington DC weren't sure that they were going to be able to start in July because their positions were those kinds of positions that were under the current hiring freeze that just was thrown out there and it took until last Thursday for the leadership to realize that oh, uh, we didn't mean them. They could come on and join in July. But those same fellows we're given an option to say, well, if you don't believe that, that's gonna be there for very long. In which case I'm talking about the NCI. You can go and maybe get a job for some other place, but there aren't gonna be other jobs. Right? So, these are people who their entire lives have dedicated to this prospect, have thought that they have just matched and what might be the most stable organization around the country, the National Cancer Institute, to only find out it might be one of the least stable.
And I was reflecting, as many have been reflecting on these just callous, huge government cuts that have been made just over the last week or so at the FDA. Some of the best minds there gone at the NCI, at the NIH, some of the best minds there gone. Let's think about that a second. So the director of the Institute of Nursing Research gone, the head of the National Institute of Minority Health, health Disparities gone. The director of the Institute of Child Health and Human Development gone along with many others just on a dime, right?
They're using a model of a game show, a TV evening show, where the answer is you're fired. So we just fire people because we don't like what shirt they're wearing or where they park their car or some stupid answer like that. And I know it's so disruptive to everybody figuring out what does tomorrow hold? When's somebody gonna come and knock at your door? et cetera. So we are all in shock as an academic institution.
Who's the next Columbia? Apparently, it might be Harvard. They're going after them. How do we work together? NCI designated cancer centers to make sure that the administration and the house, et cetera. Understand the importance of our collaborative research and how we have contributed and will continue to contribute to the cures for cancer and other diseases.
Now the last piece of this is that, you know, as we talked about before, don't worry because Donald Trump and his administration is gonna cure cancer. Now, if you believe that, then sit back and let all of this just go. Leave them in charge. Let 'em do what they wanna do, because don't worry. Trust me, they're gonna cure cancer in four years. My argument is that that's unlikely at best, right? The kind of investment, the kind of people that have been fired, the kind of things that are going on is gonna reverse this process. If anything, and don't get me wrong, I would love to be wrong about this, but I don't think I am. And so how are we as a community, a medical healthcare community? How are we as a research community, how are we, are we as a drug development industry? To ensure that we keep the bar moving forward, that we provide care for our patients, that we innovate, and that we indeed do reach the same goal that our administration is seeking, and that is to cure cancer, but actually do it in as fast a timeline as we can.
We're gonna have to step out of our foxholes. We're going to have to look down the street, talk to each other, collaborate. Scream out loud when it's important. Stand up in front of Congress for 25 hours in a row and make sure they know that we're not happy with what's going on. The rest of the world is extremely unsettled. We are extremely unsettled. I think we should not just sit back and let it be. I think we should figure out how to work together, how to make larger voices, push back and say, there are some things that you are doing that are just not right, and we want it fixed.
John Marshall for Oncology Unscripted.