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The PancChat Podcast is a collaborative effort from Let’s Win Pancreatic Cancer and the Pancreatic Cancer Action Network (PanCAN), inspired by the long-running #PancChat Twitter/X chat.
Hosted by award-winning journalist Alisyn Camerota, each episode features conversations with leading researchers, clinicians, patients, and advocates who are shaping the future of pancreatic cancer care and research. Together, we deliver expert insights, personal journeys, and the latest breakthroughs—bridging the gap between science and lived experience.
Whether you’re a patient, caregiver, healthcare professional, or simply want to learn more, join us to connect, be inspired, and learn how you can help to accelerate progress in the fight against pancreatic cancer.
Cindy Gavin: Hi everyone. I'm Cindy Gavin, CEO and co-founder of Let's Win Pancreatic Cancer. On today's podcast, we will take a closer look at the different treatment options for pancreatic cancer. Now over to you, Alisyn.
Alisyn Camerota: Hi everyone. Welcome to episode five of PancChat. Today's episode focuses on treatment options for pancreatic cancer. I'm your host, Alisyn Camerota. We want to thank our sponsor, Revolution Medicines.
So let me introduce our guest today. Dr Michael Pishvaian is the Director of Gastrointestinal Developmental Therapeutics and Clinical Research Programs for the Johns Hopkins Kimmel Cancer Center in the Greater Washington DC area and an Associate Professor at the School of Medicine. Welcome, doctor.
Dr. Michael Pishvaian: Thank you so much for having me.
Alisyn Camerota: Thanks for being here. Let’s just start with the basics if we can. When someone is diagnosed with pancreatic cancer, they are often offered standard of care treatment. Can you help define for us what standard of care means?
Dr. Michael Pishvaian: Yeah. Absolutely. So, standard of care really means the best that we know of to offer that patient at that given time. And we hope that standard of care improves over time as clinical trials are done. And right now, the standard of care involves primarily chemotherapy for patients with pancreatic cancer.
Alisyn Camerota: You know, I've let our audience know, I'm familiar with this because my husband passed away a year ago from pancreatic cancer. So, I remember that standard of care was one option. He was lucky enough to get on a clinical trial. And I say lucky enough because is the standard of care good enough? I mean, my impression is that people are always searching for something different than the standard of care in pancreatic cancer treatment.
Dr. Michael Pishvaian: That's a tough question. I would say for any cancer or for any disease really, the standard of care is never good enough until the cure rate is a hundred percent. But having said that, we definitely have made headway in the standard of care for pancreatic cancer, but we know that we still have a long way to go. We also know that we're woefully low in our clinical trial accrual rate. We only recruit about four percent of all pancreatic cancer patients into clinical trials.
So while we need to make progress, we really need to get more patients on trials to be able to make that progress.
Alisyn Camerota: Why is it so low, that recruitment rate?
Dr. Michael Pishvaian: So, there's a variety of reasons. Nobody knows exactly why. One of the things that we fight against the most is the nihilism, the cynicism that comes with a diagnosis of pancreatic cancer. And even in 2025, we still hear stories of family members, physicians, primary care doctors, gastroenterologists telling patients you've been diagnosed with pancreatic cancer. Don't bother getting any treatment. Just go get your affairs in order, which is really, really shameful.
And because of that, there's actually good data both from Canada and from the United States looking at insurance roles that fewer than 50% of patients who are labeled with a pancreatic cancer diagnosis get any treatment at all. Not surgery, not radiation, not chemotherapy, nothing. So, a lot of those patients, probably some of those patients are very sick and they can't get any treatment, but definitely some of those patients are being kind of guided to not undergo any treatment at all. Even of the 50% of patients who do get some sort of treatment, the lack of clinical trial enrollments definitely has a lot to do with the fact that there aren't a lot of really great clinical trials for patients. So even if we could enroll every patient into a clinical trial, we just don't have enough spots in innovative, exciting clinical trials.
And then there are logistical concerns as well. Sometimes it's just practically difficult for a patient to get into a clinical trial. You know, I think, if I'm not mistaken, you're in New York, I'm in DC, we both have multiple centers near us. But for a patient who's in Montana or even in Oregon, they have to travel sometimes six, seven, eight hours to get to a site that might have a trial that's appropriate for them.
Alisyn Camerota: Wow. That's really stunning. Thank you for all of that background. I wasn't aware of how difficult it can be because as we say, standard of care only goes so far. So, with standard of care, it means chemotherapy. Does it also mean surgery and radiation? Are those part of standard of care treatment?
Dr. Michael Pishvaian: They definitely are part of the overall armamentarium, but that definitely depends upon the stage and what the expectation is for treating that cancer. You know, a lot of patients will ask me about what stage of pancreas cancer they have, and I often forget if they're stage I or stage II in an earlier stage patient, because the reality is we really only focus on three characteristics of a patient's cancer when they're newly diagnosed. They're either clearly operable from the get go, so they're resectable. They have already cancer that's cancer that's already learned to spread to another organ, and that's a stage IV cancer. And then there's essentially everything in between, the localized patients that have some degree of involvement of the local blood vessels making surgery direct surgery more challenging.
Alisyn Camerota: I mean, I know that everyone is always gunning for surgery. What is the, and I don't know if you have this figure off the top of your head, but what's the general percentage of people who are eligible for surgery?
Dr. Michael Pishvaian: That's only about 10% of patients who are eligible from the get-go. These cancers learn to grow very quietly, very subtly. Patients might have the just the vaguest of symptoms over sometimes months or sometimes even a year or two before the cancer actually becomes diagnosed, and so the cancers learn to spread very early on. So 55% of patients when they are diagnosed already have stage IV cancer and 30% percent, 30 to 35%, their cancer is already involving or wrapped around some of the critical blood vessels that make surgery very difficult.
Alisyn Camerota: So really, as you say, only 10% are eligible for surgery. And what is their, I mean, I know that you can't generalize, but that's the best prognosis if you can get surgery. Yes?
Dr. Michael Pishvaian: So far to date, the only way that we know how to cure a patient with pancreatic cancer is if they ultimately have surgery, whether that's before or after chemotherapy, but ultimately surgery is the only way to cure them. Our rates of cure have definitely gone up in the last thirty years. You know, 30 years ago, the rate of cure with surgery was under five percent, probably like one or two percent. With chemotherapy being given postoperatively, those rates have significantly improved. It's still only a little less than 50%.
So about 40% of patients under the best of circumstances are ultimately cured with a combination of surgery and chemotherapy plus minus radiation. There's a lot of controversy about that, but surgery and chemotherapy can achieve about a 40, maybe up to 50% cure rate in a patient with pancreatic cancer.
Alisyn Camerota: Let's talk about the role of radiation. So, radiation, is it always used in conjunction with something else or can it be used just alone?
Dr. Michael Pishvaian: It can definitely be used alone. It definitely depends on the goal of the radiation therapy. I refer a lot of patients with pancreatic cancer to radiation therapy because radiation can be very effective at treating the symptoms that come from the tumor. If it's a tumor in the pancreas, it can control pain and other symptoms that are coming from that tumor. If it's a metastasis that has spread to another part of the body, that again is causing symptoms such as pain, then the radiation can be very effective at treating that area as well.
What we don't know even up to today is whether radiation actually helps cure patients at all. In fact, there have been multiple, multiple studies and we've really never proven that radiation increases the cure rates. There's a lot of secondary studies and a lot of pointing that there are some patients for whom radiation is beneficial, but we really haven't been able to nail that down. There's many, many other studies that are in development or ongoing trying to answer that question definitively.
Alisyn Camerota: That's really interesting. So basically, at the moment, in terms of standard of care, you're using the radiation in a palliative way?
Dr. Michael Pishvaian: In a palliative way and then I would say in the most selected population of patients that's being decided in a multidisciplinary fashion that's really critical where the surgeons, the medical oncologists and the radiation oncologists are discussing together. Sometimes we are also incorporating radiation therapy with curative intent.
Alisyn Camerota: Let's talk about chemotherapy. So there many different chemotypes that you use for pancreatic cancer or is it mostly FOLFIRINOX?
Dr. Michael Pishvaian: There's only really two types, maybe three. I often joke with my fellows that, pancreatic cancer amongst the GI cancers is probably the cancer for people who aren't so smart to learn to treat because you only have two real choices. Cancers like colorectal cancer have become very complicated. Gastric cancer has become very complicated and complicated in a good way because you have so many things, so many different ways to treat patients. For pancreatic cancer, we're still really sort of reliant on two standard of care regimens and I'll mention a third and second.
So first of all, as a background, back in the 90's, there was really very little to offer patients in terms of chemotherapy, but from the late 1990s through to the mid two thousand teens or early two thousand teens, the only drug we really used was a drug called gemcitabine. There was another drug, 5-FU, which probably worked as well as gemcitabine, but the gemcitabine was generally better tolerated and so we used that preferentially. And gemcitabine didn't do much. It really kind of slowed the decline of a patient, but never, you never really saw patients get much better with gemcitabine. But in 2011, we had the FOLFIRINOX study, which is a combination of three chemotherapy drugs, 5-FU, oxaliplatin, and irinotecan, and those three combined together were clearly better than gemcitabine alone.
Couple years after that, we had the combination of gemcitabine and nab-paclitaxel, many people will know it as Abraxane, but gemcitabine and Abraxane was also clearly better than gemcitabine alone. And that's really been our two standards for the last now 14 years. There's another, one other combination that patients may have heard of, which is gemcitabine and cisplatin, which is a combination that is appropriate to use for patients who are newly diagnosed and have the right kind of mutational status. And then finally, there's another three drug combination that we call NALIRIFOX. NALIRIFOX is basically the same as FOLFIRINOX, but instead of irinotecan, what we call naked irinotecan, it utilizes an encapsulated irinotecan called nanoliposomal irinotecan.
But for now, we don't really know that NALIRIFOX is any better than FOLFIRINOX. So when I use the term FOLFIRINOX, I could very easily be saying NALIRIFOX as well and that's probably gonna be true throughout this discussion.
Alisyn Camerota: And NALIRIFOX, is it better now that it's newer, is it, better tolerated than FOLFIRINOX?
Dr. Michael Pishvaian: No. The study that was done, they looked at quality of life outcomes and the quality of life metrics that they measured for patients who are on NALIRIFOX were better than for patients who had received FOLFIRNOX as part of some of the critical trials 10 years earlier. The problem with that assessment is it's really not an apples to apples comparison. And the way we use FOLFIRINOX today is very different from how FOLFIRINOX was originally used in the French study in 2011. And my experience and many of my colleagues experience with FOLFIRINOX and the side effects and how well patients tolerate is really about the same as what was reported in the NAPOLI-3 NALIRIFOX study.
Alisyn Camerota: So when a patient comes to you and presents with, you know, a new diagnosis of pancreatic cancer, how do you decide which of these they're going to get?
Dr. Michael Pishvaian: Yeah. So there have been multiple studies that have tried to ascertain which is better: gemcitabine, nab-paclitaxel or FOLFIRINOX. And we still to this day are that debate is kind of raging. And it's gone back and forth when the gemcitabine, nab-paclitaxel trial came out, it was two years after FOLFIRINOX and numerically the FOLFIRINOX data was better. There was a better survival, a better shrinkage, tumor shrinkage rate, what we call response rate.
But there were a lot of caveats to that, including the fact that the patient population who was treated with gemcitabine, nab paclitaxel was a little bit older, a little bit sicker. So again, it wasn't an apples to apples comparison. And in fact, over the next ten years, there were several large sort of registry or database trials looking at the comparison of these two. And there was a lot of discussion that actually they look very, very similar. When the NAPOLI-3 trial came out, it was the first real prospective trial where patients were enrolled and were randomized, by the flip of a coin to either receive a three-drug cocktail NALIRIFOX or the two-drug cocktail gemcitabine, nab-paclitaxel.
And in that specific trial, there's no question, and it was a well-run trial that the NALIRIFOX did better than the gemcitabine, nab-paclitaxel. And many people have extrapolated that to say, okay, three drug treatment is better than two drug treatment. But there have been other studies, still modern studies that have refuted that including, for example, there's a Japanese study, granted the Japanese East Asian population, we know as a general rule of thumb, just do a little bit differently, tolerate things a little bit differently than the Western population. And in their hands, in their critical trial, the gem study in nab-paclitaxel was clearly better than FOLFIRINOX. And then most recently there was a phase II study, but nevertheless a well-run rather large phase II study called the PASS-01 study that compared nab-paclitaxel/gemcitabine to and it was completely equivalent.
No difference at all in the different, in the two groups. So one could really get lost in the debate and I think that that's why we have to factor in other features of the patient in front of you in deciding which one you're going to use. First of all, we know that FOLFIRINOX and NALIRIFOX are a little bit harder to tolerate than gemcitabine/nab-paclitaxel. And so, we know that sort of an older, frailer patient population probably can't tolerate FOLFIRONOX. And those are the patients that will use gemcitabine/nab-paclitaxel for.
There are certain biomarker subgroups of patients, patients who have certain genetic mutations. If you happen to know that upfront, that you might prefer to use NALIRIFOX or FOLFIRINOX. And then finally patient decision weighs heavily, at least for me when I'm discussing things with patients. If I'm dealing with a patient with stage IV disease that we've had the discussion that we can't cure their cancer and that extension of life is equally important to quality of life. I have definitely had patients that choose from a quality of life perspective, not to be treated with FOLFIRINOX because they don't want to deal with the side effects, including they don't want to deal with the 5-FU pump that they have to wear for two days.
And so even a fit healthy patient, I've treated with gemcitabine/nab-paclitaxel, in sort of that patient discussion shared decision-making process.
Alisyn Camerota: So, with other chemotherapies other than the FOLFIRINOX family, you don't have to wear a pump. How does it get administered?
Dr. Michael Pishvaian: Yep, so all of these chemotherapies go in through the vein, they're all IV. But 20 years ago, was realized that giving the 5-fluorouracil, 5-FU, it's metabolized very quickly in the body, like within seconds. And so, to give a bolus of it, to give a large dose of it, and then just that, get that treatment once every couple of weeks doesn't do as much as if you give it slowly. And so the way we give FOLFIRINOX and is you give the 5-FU slowly over 46 hours, not 48 hours, but 46 hours. And then you have to wear a pump that pumps that in slowly over 46 hours. So patients go home with the pump, they carry it around with them.
It becomes, you know, it becomes their appendage, they get used to it, but it's certainly awkward at first.
Alisyn Camerota: It's just amazing how fluent you are in this whole language. I mean, you're reminding me now. It is a language of its own. All of these FOLFIRINOXES and all of the different options. And, you know, sadly, people become familiar with this.
Dr. Michael Pishvaian: It's true. I got it. The analogy that I use for patients with their pump is I say, you know, it's like somebody who broke their leg and they have no choice but to get used to the crutches that they're using within the first couple of days and it's the same way with the pump.
Alisyn Camerota: It's so true and with the pump it actually doesn't actually also make a noise?
Dr. Michael Pishvaian: It makes a very faint whirring noise. Yes, some people can get discomfort with that.
Alisyn Camerota: Yeah. And so doctor, I mean, I don't mean to put you on the spot, but when a when a patient comes to you and presents with stage IV pancreatic cancer, do you do you go, is your first instinct to go standard of care or do you look around for every other option first?
Dr. Michael Pishvaian: I definitely consider myself a clinical trialist and so my first go-to is absolutely to get them on a clinical trial and I will go out of my way to find them an appropriate clinical trial. As I mentioned earlier, we have the luxury of having, a couple of great centers just within driving distance that might have different trials that patients can have access to. Where I practice, there are definitely, it's actually a real mix of patients, but some of the patients have the means to go anywhere. And so if I've got a friend in San Francisco, who's got a really, really great innovative trial, I'd be happy to refer them over there. So trials are definitely my first choice.
It's just that we have so few trial options and even if there are good trials, there are so few spots on those trials. So I do end up somewhat disappointed. I'm disappointed in myself that I give standard of care a lot. I wish many more of my patients were on clinical trials. I will tell you that I used the number four percent earlier that we know that 4% of patients, in with pancreatic cancer are put on clinical trials nationally.
If a center is doing really, really well, you know, receive high praise if they actually enroll 20% of their patients on clinical trials. And I know at my center, at Hopkins, back in the heyday 10 years ago, we were enrolling 50% of our patients on pancreatic cancer trials, which is kind of unheard of. So you're never going to get 100% of your patients on a clinical trial.
Alisyn Camerota: You know, I remember hearing about people who were traveling for clinical trials hearing about patients, But the rub is that you don't just have to go to Portland, Oregon once. I mean, you have to kind of decamp and live there. Right?
Dr. Michael Pishvaian: It's true. Some of the trial designs are have become more innovative or more flexible with patient care. There are several large national trials right now that for example, if they're getting, if some component of their treatment is an experimental component and they don't need to be there for every treatment, then they can get their chemotherapy. If it's added to chemotherapy, they can get their standard chemotherapy at their home oncologist's office, but then just come periodically. But you're right, most of the trials, you have to be there on a recurring basis.
I remember when I was in Houston, I was down at MD Anderson for just a year and there was a whole trailer park of patients who were on clinical trials and used to drive their trailer down there and stay there for months at a time just to be able to stay on the trial.
Alisyn Camerota: Wow. Yeah. That's a fact. And so, doctor, what's the takeaway from all of this? I mean, for the patients and their families who are listening, what should they do to be proactive and particularly if standard of care is all their doctor is offering?
Dr. Michael Pishvaian: Well, they should definitely talk about clinical trials. They should definitely raise the discussion acknowledging that many people don't have access to these trials, but they should at least bring that up because if we don't have a trial for patient as they're starting their chemotherapy, then we definitely may have trials for them later on in the course of their therapy, either when what we call maintenance therapy or in second line or beyond. So clinical trials should always be a thought if the right trial comes up at the right time. And then I think that, you know, none of, we don't mind patients that come to us with a list of possible trials. The problem is, and this is not the fault of the patient at all, is that the lists that are out there, for example, on ClinicalTrials.gov, they're thorough, but they don't really tell you which trials are truly available for that patient at the right time.
So that's the hard part too. But yeah, the more informed a patient can be, they shouldn't hesitate to ask their doctor, are there clinical trials either here or nearby that I can go to that might actually give me a better option?
Alisyn Camerota: But I think that you make a very good point that I want to underscore, which is you can start on standard of care, and you can get some runway with standard of care. I mean, you can you can that can work for you, and then you can while you're looking for your next, you know, vine to swing through.
Dr. Michael Pishvaian: And again, many of us are getting that message. We I just had an hour long call this morning. We're designing a new trial with FOLFIRINOX and actually we are definitely baking into the protocol that patients can have received one or two doses of their FOLFIRINOX and then be enrolled in the study and they're still considered first line treatment.
Alisyn Camerota: That's really valuable because you would hate to be blocked, you know, from getting into a clinical trial just because you did something that was the most you know, it's such a time sensitive situation that you definitely wanna act with alacrity, then you would hate to be cut out of a clinical trial.
Dr. Michael Pishvaian: It's true. It's happened to me. In fact, happened to me recently where a patient literally just missed the window for a trial by hours and it's really heartbreaking.
Alisyn Camerota: Yeah, that is heartbreaking. Right, doctor, thank you. This is so helpful. What have I missed? Is there anything else you want to say about standard of care or any kind of treatment that I think?
Dr. Michael Pishvaian: Well, I think one thing we didn't really talk about is the effectiveness of standard of care. And I won't go into a whole lot of details on numbers and stuff like that. But what I will say really as a counter argument to that cynicism that I discussed earlier, is that chemotherapy, standard of care chemotherapy does definitely help patients with pancreatic cancer. In fact, numerically, statistically, the majority of patients, probably about 80% of patients will have some benefit from the chemotherapy, whether it's FOLFIRINOX or gemcitabine, nab-paclitaxel. That means a reduction in their pain and improvement in their quality of life and improvement in how they're feeling overall.
So chemotherapy definitely can work. It has a time limit as to how long it works for, but it definitely can work.
Alisyn Camerota: That is such a great point and I'm really glad that you're making it. But when you say it has a time limit, can you put a finer point on that?
Dr. Michael Pishvaian: You know, that's where I think an individual patient discussion is really important because sometimes patient people don't like to dwell on the numbers. And I definitely emphasize the idea that every person is different. And I there's nothing about the patient in front of you that tells you if they're going to have a very little benefit from the chemotherapy and their cancer is going to grow rapidly, or if they're going to be those patients who for reasons that we can't explain are on their treatment for sometimes years.
Alisyn Camerota: Yeah, so in other words, the standard of care can last a long time, but you don't know it going in.
Dr. Michael Pishvaian: Yep, it's true. So it's really important to manage the side effects, to focus very much on quality of life, and then take it basically one treatment and one scan at a time.
Alisyn Camerota: Dr. Michael Pishvaian, thank you so much. Really great information. Sure that our viewers will really appreciate hearing all of this.
Dr. Michael Pishvaian: Excellent. My pleasure. Thanks so much.
Alisyn Camerota: Okay. Thank you. And thanks everybody for tuning in. I'll see you next time.
Julie Fleshman: Hi, I'm Julie Fleshman, President and CEO of PanCAN. Thank you for listening to this episode about pancreatic cancer treatment. For more information, please visit pancan.org and letswinpc.org. In our next episode, Dr. Andrew Hendifar will join us to talk about how treatment decisions are made and how clinical trials may fit into care planning.
We hope you'll join us.