Pancreatic cancer has always been a tough disease to treat, but glimmers of light are leading to progress. Watch as Dr Marshall digs into to new promise for pancreatic cancer care.
MedBuzz: The PBM Pushback
[00:00:00]
John Marshall, MD: Ho, Ho, Ho, everybody out there. This is John Marshall for Oncology Unscripted, and we're going to talk a lot about pancreatic cancer today. We're also going to talk about some other things as well, but I thought I would sort of start off with a little holiday story.
See that stocking? I've had this stocking for a long, long time. I actually keep it right over there in my drawer, and it's a reminder of what we do for a living. So, a patient almost 30 years ago gave me this. It was actually a breast cancer patient I was covering for one of my colleagues who was out on maternity leave, and during that three-month window, I was the one who gave her the scan that showed the recurrence of her breast cancer. And so, I was the messenger if you will, of the bad news. And she pretended like nothing was really a big deal, and it was fine. My colleague came back and managed things from that point on. But then that Christmas season, that year, I got a very beautifully wrapped box. I thought, oh, how nice that this patient I was covering for those three months, many years ago had given me this gift and I opened it up and inside was this stocking. I thought, well, that's pretty nice. I don't really understand it. And then I felt and inside the stocking is a lump of coal. And this was a patient who had taken a lot of trouble to wrap me up a pretty gift with a stocking in it, mainly to make sure I knew that I was the Scrooge for her holiday season.
And so, as we enter this holiday season with our patients, with our colleagues and our teams around us, remember. It is a special time of year for all of us. It's an important time of year, but it's also a time of year when bad news carries a little bit harder weight with our patients. So, avoid getting one of these from your next patient if you get one of those bad scans, which sadly is common among our pancreas cancer patients.
But before we go there. talk a little bit about one of our past topics, a little bit of gossip that's out there, and that's the pharmacy benefit manager. If you remember, we talked about this a few episodes ago where this group CVS Caremark, and there are many of them now, nearly three big ones, are controlling the pricing of our medicines in such a way that they're ramping up pricing, controlling the distribution, and really kind of undermining a lot of the free enterprise, if you will, out there. And so I'm sure it wasn't our video and commentary that caused this, but there's been some backlash from the PBMs who now are like filing lawsuits against the Federal Trade Commission, claiming that basically they're fiddling with all of this is unconstitutional. And they've had full page ads running in the Washington Post. We always know when there's something going on here in Washington because they'll take out a full-page ad saying we're right. You're wrong. You should support us. I guess it’s sort of subliminal messaging for our Congress people as they go to work in the morning. Nonetheless, there's now this pushback from PBMs to say, stay out of my business. It's not the government's business.
And so now I'm thinking about what's coming in the year ahead. You don't want regulation. Okay, you voted for him. He's not going to have any regulation, at least as far as I can tell. But this is one of those examples of what's going to happen if we don't push back, it's going to affect all of us going to affect the cost of health care. And we won't be the ones who are benefiting from this. These third-party managers, such as the PBMs, will be the ones that are benefiting. So, it's going to be to see what happens in the year ahead. Just how much changes in regulation, particularly for us in health care, will have an impact on outcomes, cost, access, all those important things that we are trying to get for our patients. So, I don't know. Stay tuned. More stories to come on the PBMs.
What’s Making the Impossible Possible in Pancreatic Cancer?
[00:04:19]
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.
Shaping the Future of Pancreatic Cancer: Interview with Julie Fleshman
[00:11:20]
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. It's always a pleasure to talk to you and be with you.
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? And about that. 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 was 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 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 that.
Julie Fleshman: So yes, so you know, and it was one of the colors not taken, right? 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, but all kidding aside, I mean, you and your team have built an incredible infrastructure, not just a Hill presence and 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, hopefully it will also help 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: Yeah, I couldn't agree more. Now, the year ahead, we're all pretty sure that the NIH budget is not going to get bigger. We're panicked that it's going to be significantly smaller. And so, I think about a group like yours that has successfully advocated in DOD budget, negotiations to get pancreas cancer research funded there, there's certainly a high priority around pancreatic cancer in the NIH budget.
What are some of your worries as you look to the year ahead and new administration changes?
Julie Fleshman: Yeah, I was actually just on Capitol Hill last week with Madison Marsh, Miss America 2024, who lost her mom to pancreatic cancer. And so, she's been using her platform to talk about the disease. So, she and I were up on the Hill together and talking about increasing the DOD line item for pancreatic cancer research, and just trying to understand the current environment. And definitely what we heard is most likely it will be flat funding. There probably will not be any increases. And I think there is just a lot of concern about what's going to happen to these agencies and what could this look like. So, PanCAN along with the other cancer advocacy organizations are going to have to stay on top of it. I think the good news is that usually health related problems do better during change like this. And so, let's hope that's the case, but this will be a time where the voice of the patient, the voice of advocates is going to be extremely important.
John Marshall, MD: 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. 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 that sort of process, and does this platform concept work? And I think the answer is yes. However, financially, in order to make it financially work, you have to have constantly have new drugs coming into the pipeline on the platform. And that was the part that turned out to be 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.
We also had, you know, the last couple of years it's better today, but the last couple of years, I mean the funding for biotech, you know, really dried up. I still think many of them are challenged and so there wasn't even funding to do something even like this that would be less expensive. So, with all of those things, it became a financial risk for PanCAN was the bottom line.
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 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 big, you know, basically phase three clinical trial for an organization like us that had never operated one before. So, you know, we didn't have everything working with us, we did this, but we certainly learned a lot.
And I think, you know, 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 just held here at Georgetown at the Reusch Center, a think tank around pancreatic cancer. And 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, or 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, 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.
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 for 25 years, I've been told KRAS, RAS 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 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. 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 in September. 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.
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 that's driven this and made sure that in the top of everybody's mind is how We're all tired of taking care of pancreas cancer patients with not much to do. 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 for talking with us today 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 all you do for patients. So, thank you.
John Marshall, MD: I really can't thank Julie enough for joining us in our series Oncology Unscripted. As you can see from our discussion, she’s just all there is out there. She has been such an advocate and positive for so many of us in the space of GI cancers and pancreas cancer in specific. So, a great shout out to her and thank everyone out there for joining us today as we've sort of started to dig in deeper in the world of pancreatic cancer, our hope for the future, as we've developed new agents and new support for our patients that are out there. Join us next time on Oncology Unscripted.
Thanks everybody. John Marshall.
Oncology Unscripted With John Marshall: Episode 11: What’s Making the Impossible Possible in Pancreatic Cancer?
MedBuzz: The PBM Pushback
[00:00:00]
John Marshall, MD: Ho, Ho, Ho, everybody out there. This is John Marshall for Oncology Unscripted, and we're going to talk a lot about pancreatic cancer today. We're also going to talk about some other things as well, but I thought I would sort of start off with a little holiday story.
See that stocking? I've had this stocking for a long, long time. I actually keep it right over there in my drawer, and it's a reminder of what we do for a living. So, a patient almost 30 years ago gave me this. It was actually a breast cancer patient I was covering for one of my colleagues who was out on maternity leave, and during that three-month window, I was the one who gave her the scan that showed the recurrence of her breast cancer. And so, I was the messenger if you will, of the bad news. And she pretended like nothing was really a big deal, and it was fine. My colleague came back and managed things from that point on. But then that Christmas season, that year, I got a very beautifully wrapped box. I thought, oh, how nice that this patient I was covering for those three months, many years ago had given me this gift and I opened it up and inside was this stocking. I thought, well, that's pretty nice. I don't really understand it. And then I felt and inside the stocking is a lump of coal. And this was a patient who had taken a lot of trouble to wrap me up a pretty gift with a stocking in it, mainly to make sure I knew that I was the Scrooge for her holiday season.
And so, as we enter this holiday season with our patients, with our colleagues and our teams around us, remember. It is a special time of year for all of us. It's an important time of year, but it's also a time of year when bad news carries a little bit harder weight with our patients. So, avoid getting one of these from your next patient if you get one of those bad scans, which sadly is common among our pancreas cancer patients.
But before we go there. talk a little bit about one of our past topics, a little bit of gossip that's out there, and that's the pharmacy benefit manager. If you remember, we talked about this a few episodes ago where this group CVS Caremark, and there are many of them now, nearly three big ones, are controlling the pricing of our medicines in such a way that they're ramping up pricing, controlling the distribution, and really kind of undermining a lot of the free enterprise, if you will, out there. And so I'm sure it wasn't our video and commentary that caused this, but there's been some backlash from the PBMs who now are like filing lawsuits against the Federal Trade Commission, claiming that basically they're fiddling with all of this is unconstitutional. And they've had full page ads running in the Washington Post. We always know when there's something going on here in Washington because they'll take out a full-page ad saying we're right. You're wrong. You should support us. I guess it’s sort of subliminal messaging for our Congress people as they go to work in the morning. Nonetheless, there's now this pushback from PBMs to say, stay out of my business. It's not the government's business.
And so now I'm thinking about what's coming in the year ahead. You don't want regulation. Okay, you voted for him. He's not going to have any regulation, at least as far as I can tell. But this is one of those examples of what's going to happen if we don't push back, it's going to affect all of us going to affect the cost of health care. And we won't be the ones who are benefiting from this. These third-party managers, such as the PBMs, will be the ones that are benefiting. So, it's going to be to see what happens in the year ahead. Just how much changes in regulation, particularly for us in health care, will have an impact on outcomes, cost, access, all those important things that we are trying to get for our patients. So, I don't know. Stay tuned. More stories to come on the PBMs.
What’s Making the Impossible Possible in Pancreatic Cancer?
[00:04:19]
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 inthe 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, becausewe'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.
Shaping the Future of Pancreatic Cancer: Interview with Julie Fleshman
[00:11:20]
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. It's always a pleasure to talk to you and be with you.
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? And about that. 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 was 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 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 that.
Julie Fleshman: So yes, so you know, and it was one of the colors not taken, right? 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, but all kidding aside, I mean, you and your team have built an incredible infrastructure, not just a Hill presence and 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, hopefully it will also help 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: Yeah, I couldn't agree more. Now, the year ahead, we're all pretty sure that the NIH budget is not going to get bigger. We're panicked that it's going to be significantly smaller. And so, I think about a group like yours that has successfully advocated in DOD budget, negotiations to get pancreas cancer research funded there, there's certainly a high priority around pancreatic cancer in the NIH budget.
What are some of your worries as you look to the year ahead and new administration changes?
Julie Fleshman: Yeah, I was actually just on Capitol Hill last week with Madison Marsh, Miss America 2024, who lost her mom to pancreatic cancer. And so, she's been using her platform to talk about the disease. So, she and I were up on the Hill together and talking about increasing the DOD line item for pancreatic cancer research, and just trying to understand the current environment. And definitely what we heard is most likely it will be flat funding. There probably will not be any increases. And I think there is just a lot of concern about what's going to happen to these agencies and what could this look like. So, PanCAN along with the other cancer advocacy organizations are going to have to stay on top of it. I think the good news is that usually health related problems do better during change like this. And so, let's hope that's the case, but this will be a time where the voice of the patient, the voice of advocates is going to be extremely important.
John Marshall, MD: 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. 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 that sort of process, and does this platform concept work? And I think the answer is yes. However, financially, in order to make it financially work, you have to have constantly have new drugs coming into the pipeline on the platform. And that was the part that turned out to be 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.
We also had, you know, the last couple of years it's better today, but the last couple of years, I mean the funding for biotech, you know, really dried up. I still think many of them are challenged and so there wasn't even funding to do something even like this that would be less expensive. So, with all of those things, it became a financial risk for PanCAN was the bottom line.
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 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 big, you know, basically phase three clinical trial for an organization like us that had never operated one before. So, you know, we didn't have everything working with us, we did this, but we certainly learned a lot.
And I think, you know, 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 just held here at Georgetown at the Reusch Center, a think tank around pancreatic cancer. And 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, or 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, 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.
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 for 25 years, I've been told KRAS, RAS 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 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 ofresponders in those patients.
Julie Fleshman: Absolutely. 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 in September. 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.
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 that's driven this and made sure that in the top of everybody's mind is how We're all tired of taking care of pancreas cancer patients with not much to do. 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 for talking with us today 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 all you do for patients. So, thank you.
John Marshall, MD: I really can't thank Julie enough for joining us in our series Oncology Unscripted. As you can see from our discussion, she’s just all there is out there. She has been such an advocate and positive for so many of us in the space of GI cancers and pancreas cancer in specific. So, a great shout out to her and thank everyone out there for joining us today as we've sort of started to dig in deeper in the world of pancreatic cancer, our hope for the future, as we've developed new agents and new support for our patients that are out there. Join us next time on Oncology Unscripted.
Thanks everybody. John Marshall.
This transcript has been edited for clarity.