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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. What an exciting time for the pancreatic cancer community. On August 26, the FDA approved RasonqueTM, the first ever drug to directly target the RAS mutations that drive the majority of pancreatic cancers. This is a landmark moment for our community.
On today's podcast, we will learn more about the new drug and how it will be used, as well as what it means for patients and for the future of research.
Over to you, Alisyn.
Alisyn Camerota: Hi everyone. Welcome into PancChat. I'm your host, Alisyn Camerota. Before we get started, we want to thank our sponsor Revolution Medicines. Today's episode is very timely because it focuses on the big news surrounding the FDA's approval of this groundbreaking first of its kind pill to treat the KRAS mutation which has been such a vexing problem for doctors and researchers trying to treat pancreatic cancer.
Allow me to introduce our guest Dr. Brian Wolpin. Dr. Wolpin has been on staff at the Dana Farber Cancer Institute and Harvard Medical School since 2007 where he currently serves as the Robert T. and Judith B.
Hale Chair in Pancreatic Cancer and Professor of Medicine. His research focuses on designing approaches for early detection and studying novel therapeutics for pancreatic cancer. He and his research team have been at the forefront of studying RAS inhibitors in the laboratory and in the clinic, so he is a great authority to help us understand where we are today with this development. Welcome, Dr. Wolpin.
Dr. Brian Wolpin: Well, thank you, thanks for having me.
Alisyn Camerota: Thanks for being here. Okay so let's start with the big news that the FDA fast tracked approval of this very promising drug. The brand name is RasonqueTM. RasonqueTM? Okay, making sure I have that right.
Which is manufactured by our sponsor RevMed. And in the interest of full disclosure, I should say my husband was part of the phase one clinical trial for this drug. So, I saw firsthand how it worked. So, doctor, tell us what it means for pancreatic cancer patients now that this new drug was just approved by the FDA.
Dr. Brian Wolpin: Yeah, I think there's two big buckets of things it really means in my mind. The first is it provides a new treatment option for patients, which we have really desperately been looking for and working hard to achieve. And the data from the clinical trial, which we'll talk some more about, really showed that it benefits patients both in terms of quality of life, but also how long they're able to live with their cancer. So, I think the first and foremost thing that this approval does is it provides now broad access to a medicine we have seen that is effective in patients with pancreatic cancer. I think the second thing is it really shows the field the importance of targeting RAS.
As you said at the beginning, that is a very important gene that drives pancreatic cancer, and it really is the proof that if you can target that gene well, you can lead to improved treatment for pancreatic cancer. And I think that sets the field then headed off in a really productive and exciting set of directions based on that data for now years to come.
Alisyn Camerota: Is there a way to quantify how much better patients do on this than previous traditional medicines?
Dr. Brian Wolpin: Yeah, I think probably the best way to do that is to use the data from the phase three trial, which was run to compare daraxonrasib, the experimental medicine, the RAS inhibitor, to what we generally do, and what we generally do is chemotherapy. These were patients that had metastatic spread of their pancreatic cancer, so to the liver or to the lungs or other places in the body, and they had had one prior type of chemotherapy before. In that setting, we usually switch and give them different chemotherapy because mostly what we've had available to treat pancreatic cancer has been chemotherapy.
So, in this trial, half of the patients went on to get what we would normally do, which is the chemotherapy, and half of the patients received the new medicine, daraxonrasib, and what daraxonrasib showed is that it approximately doubled the average amount of time that people lived with their pancreatic cancer. It did the same for the amount of time until the cancer developed progression.
It also led to about a threefold increase in your ability to substantially shrink the tumor, and the quality of life of patients was better preserved. There were generally less side effects from the pill medicine, the daraxonrasib, and patients' disease, their cancer was controlled for longer and better, so they also had less symptoms from their cancer. So, I think you could use all those different metrics to show that receiving daraxonrasib was better than receiving chemotherapy in this setting.
Alisyn Camerota: So, who's eligible for this new drug? Can anyone get it?
Dr. Brian Wolpin: So, I think to answer that question we need to look at the FDA approval that just occurred. When drugs are FDA approved they are given a label which describes who are appropriate patients to be treated. I would say there's three sort of main points to that that I think is worth pointing out. The first is that patients must have metastatic pancreatic cancer. So again, the cancer must have spread to other parts of the body.
Two is they must have received one prior type of chemotherapy before. Or three, if they had not received prior chemotherapy before, it must be because they're not able to do so, meaning they're not well enough to receive chemotherapy, and we don't think that they'll be able to tolerate or handle that. So, these metrics that the FDA sets down largely mirror what the clinical trial also did, right? It's really trying to say here's what the trial showed, here were the patients on the trial, and the approval largely mirrors what was present for enrolling patients to that trial.
Alisyn Camerota: So okay, does that mean that now everyone with that criteria can get this? In other words, is it available at most all treatment centers now?
Dr. Brian Wolpin: It should be. They'll take a little bit of time for stocks to come in and pharmacies to have the medicine available, but it now has a full FDA approval which allows oncologists at any cancer center or any clinic in the country to write for this medicine for their patients. So, as you had asked at the beginning about the sort of what are the big impacts of this, one is now this broad availability, right? It now becomes available. You don't have to be on a trial anymore.
You don't have to be in a special program. Any oncologist can help write this medicine for their patient if it's appropriate for them.
Alisyn Camerota: I read that a one month supply will cost roughly $40,000 which is obviously prohibitive for most American families. So how does that work?
Dr. Brian Wolpin: Yeah, so most medications, whether it be this one or others, we have health insurance that helps us try to pay for the medicines that we use like we do for, you know, any condition. The payment ultimately will be dependent upon the insurance companies and Revolution Medicines deciding upon the cost and the reimbursement. I think as with many medicines we use, it is difficult for people who don't have insurance because many medicines we use are expensive and that's really why insurance is necessary, right, for the populace.
Alisyn Camerota: Can you, you touched on this, but in layman's terms, can you just explain how this drug works and why it's so much better than chemotherapy so far?
Dr. Brian Wolpin: Yeah, I think in a big picture view, the way I tend to think about this is chemotherapy is relatively nonspecific, right? It's trying to kill cells that are dividing rapidly. And since pancreatic cancer cells do divide and grow, it's really part of the definition of cancer, chemotherapy can have some effectiveness, but it also affects a lot of your normal cells that are also growing and dividing, and therefore can cause a substantial number of side effects, and the tumor cells seem to find a way around chemotherapy quickly, right? So we give chemotherapy, it does work, right? It's an important tool for us to treat pancreatic cancer, but the problem becomes cancers get smart to that and they grow anyway, and they grow through the chemotherapy.
The daraxonrasib really takes a very different approach to this. What daraxonrasib does is we say, look, we know almost all pancreatic cancers have activation of the RAS oncogene. This is a very specific gene that's present in the tumor that gets mutated or expressed in a way that drives the tumor to grow. And we know that. We actually have known that for quite some time.
What we'd want to do then is not just kill more indiscriminately cells that grow more rapidly. We want to go in and really try to hit that specific gene, that specific mechanism that is making the cancer grow. And that's what daraxonrasib does, right? It binds to and blocks the signaling that comes from RAS. And so that really hones in on, well, what makes this kind of cancer grow?
Why does pancreatic cancer grow? It does so in many ways because of RAS, and this drug now blocks the signaling that comes from RAS. So that's really a very different way to think about treatment for pancreatic cancer compared to what we have tended to do, which is with chemotherapy. And I think that's in part why it tends to be better tolerated than chemotherapy, and also why we hope it will continue to be more effective than chemotherapy as we treat more and more patients. It has been so far.
We expect that to continue.
Alisyn Camerota: What are the side effects of this new drug and how are they managed?
Dr. Brian Wolpin: Yeah, so I would say there's sort of two big bins of side effects we have seen. One is rash and two is inflammation in the gastrointestinal tract. And so the rash honestly has probably been the most problematic of them. It's an acne like rash. It can happen on the face, on the chest, and in the back.
In many patients, you know, it's not a tremendous thing. It's bothersome, but it's not particularly severe, and we have medicines to use to manage it. But there are some patients where it can be more severe. So a more significant rash that really can cause people some discomfort. And so what we've been learning to do, and I would say this is sort of learning along the way, because this is a new medicine, we've never used a medicine like this before.
So we've had to sort of figure this out as we've been treating patients. We've been starting to figure out there are some prophylactic medicines we can give. So medicines we give right as treatment starts with daraxonrasib. There's a pill we use now to do that. We recommend people use a cream on their face and their chest that is an anti-inflammatory.
And then if the rashes were to get worse, we have now some other medicines, including other pills and other creams that we've started to use that are working much better to control the rash than what we saw at the beginning, where we were, again, really just trying to figure out how this is working. So, I think over time, we will continue to get better at managing the rash. There probably will still need to be some patients who need a break from the treatment. Some of my patients I've had to say stop the treatment for a week or two to let the rash get better. That may still be necessary, but I think we're seeing that less as we're getting smarter about how to manage the rash.
That's the other
Alisyn Camerota: My husband had a little bit, a touch of it, but it wasn't worth stopping and it wasn't overwhelming. Think of former Senator Ben Sasse, who I don't know his treatment, but it appears that he has a pancreatic cancer treatment related rash and I assume he's on this drug and his was quite pronounced on his face.
Dr. Brian Wolpin: Yeah, I would say from the trials that we have done, it looks like about ten to fifteen percent of the time, people get a more severe rash. That means most people don't, right? But you definitely have to be aware of it when it starts to occur and try to treat it early. And I think the prophylaxis probably helps some too, right? Don't wait for it to happen, try to treat before it happens.
And that's not something we were doing when we first started testing this medicine. Again, we didn't know these things. This is all brand new. So, I think over time we will get better at this as we learn. You know, I think the other side effects that require some management, sometimes people need nausea medicines, right?
Because they can get some nausea from the pill. That tends to wane over time, meaning it often gets better over time, even just with time, I think the body gets used to daraxonrasib. And the same with diarrhea. Sometimes you need to take some medicines for diarrhea. But again, that has also tended to get better over time in the patients that we have treated.
Alisyn Camerota: That's great news. So, at the moment this drug, the way it's used as you've described is after the patient has exhausted the more traditional conventional route of chemotherapy. So, they've tried something else and then they get this. It's not what's called a first line treatment. Am I right about that?
Dr. Brian Wolpin: That's true. The trial was a second line treatment. So as you said, patients must have received one line of chemotherapy first and then they received the new medicine.
Alisyn Camerota: So, do we know what happens if you start with this drug?
Dr. Brian Wolpin: That's a great question. So, there is a large trial going on that is actually we hope will answer that exact question right now. So, there's a follow-up trial called RASolute 303. The prior trial was RASolute 302, was the one that was reported. So, the next trial in line is actually testing the exact question you asked, and that trial is for patients that have first line treatment, meaning they have not gotten chemotherapy before.
And that trial actually has three groups. So, patients can either be assigned to get chemotherapy, because that still is considered the standard in the first line setting. They can get daraxonrasib, or they can get the combination of the two. And the goal of that trial is to answer two different questions, right? Which is that, is daraxonrasib better than getting chemotherapy in the first line setting?
And then after that, is it useful to combine daraxonrasib with chemotherapy? And we don't know the answer to that yet. And the trial is designed to answer both of those questions, and both of those are in the first line setting, as you said.
Alisyn Camerota: I don't want to jump the gun, but do you have any insight into how it's looking on those trials?
Dr. Brian Wolpin: It's really too early to say. And you know, it's a large trial. We'll have 900 patients approximately who accrue. So, it's really hard to say that in the middle of the trial. I think we really need the trial to enroll the patients who are willing and interested to do so. And then to find out just like we did with the last trial, you know, is it beneficial compared to chemotherapy or in addition to chemotherapy?
Alisyn Camerota: So, for people who want to get into these clinical trials or, let me ask you this, are there other clinical trials happening now that also target the KRAS mutation that are not what we've been talking about that people should look into?
Dr. Brian Wolpin: Yes, very much so. So, I think daraxonrasib is sort of the first of this class to make its way through clinical trials, and now excitingly to FDA approval. But there are now quite a number of other RAS inhibitors that have entered into clinical trials. Some of them are in early trials, some actually have advanced to now phase three trials, right? Those are the large trials that the FDA generally requires to allow for approval.
So, I think these are definitely things worth when a patient develops pancreatic cancer, asking their care team about what trials do they have available at their center or clinic, and if they don't, is there a center nearby that may because daraxonrasib is sort of the beginning of this, but there are now many other drugs also that are coming that we hope will also be able to target the RAS mutation.
Alisyn Camerota: But now that daraxonrasib has been fast tracked by the FDA, is there still an advantage for people being a in clinical trial? It was hugely advantageous for my husband because it wasn't available. He happened to be in this phase one which is this very small trial and it was this very promising, groundbreaking, as I've said before, possibility. So, it was worth it for him to try it and it did work briefly for him. I mean, worked.
It worked well. We had a great quality of life and then it stopped working as often happens with these things. But that was, we felt very lucky to have access to that small phase one. But now that it's been fast tracked, is there still an advantage to people jumping on a clinical trial?
Dr. Brian Wolpin: I personally think there are often advantages to being on clinical trials, but that ultimately
is something a patient needs to review with their clinician, right? That's, we can't really make a blanket statement and say, all patients should do X or Y. Everybody is different, and I don't think it's appropriate for us to say that. But I would say that there are quite a number of promising RAS inhibitors coming, and my hope is that some of them will be equally as good, if not better, than daraxonrasib over time, or maybe some of them will not have a rash as a side effect. I think daraxonrasib is really the beginning, and they’re -- I think -- going to follow many other variations on that theme.
And if you look across sort of cancer drug development over time, generally what happens is the drugs get better, right, over time. We get smarter, we design them better, and we learn how to mitigate some of the side effects better. So over time, we generally don't end up with the same drug for twenty years. I don't think that should be our goal. Our goal is that this one works now, we help as many patients now as we can, but let's look for the next one that's going to be better than that and have less side effects than that.
And that's how I think we'll really make advances for everyone.
Alisyn Camerota: That's really heartening to hear. Okay, Dr. Wolpin, this is great information. What have
we missed? What else should our listeners know?
Dr. Brian Wolpin: Well, I think that was you know, quite comprehensive. I think really to get back to the prior question, I think it's important that patients ask their care teams about trials. I think that's an important thing for all patients to think about. Whether it ends up being appropriate for an individual patient, you know, has to be defined for them, but I think it's important for people to ask. A second thing I think is important is some of these trials are dependent upon having sequencing data from your tumor, right?
Meaning that the DNA from your cancer needs to be removed from the cancer and sequenced so we know when mutations are present. Increasingly, although this has really been considered standard of care for a while in pancreatic cancer, but increasingly, the trials around RAS inhibitors will necessitate. We have that information. So, to go on a trial, you need to know those things. So that's another thing I think is important to ask your care team, ideally even at the first visit, which is what's the plan for my tumor to get sequenced?
How are we going to do that? Because I know that that's going to have implications ultimately for what options and trials I have in the future, and I think patients should ask that. A companion to that, it's a little unrelated to our discussion today, but I always mention it anyway, which is that the other thing that's important is about ten percent of pancreatic cancer is inherited, meaning we find a mutation that someone inherited from their parents that related to their development of the cancer. That is another thing a patient should ask, which is, how are we going to figure that out? Usually it's with a blood sample, or sometimes you can do a swab in the cheek to get the DNA, but that's another thing all patients should have.
That's not as relevant for KRAS inhibitors per se, but I think as we're talking more generally about important things for patients with pancreatic cancer, that's definitely on my list where I make sure all patients have that done.
Alisyn Camerota: That's a great point. My husband and I learned through this process, you have to be your own best advocate, and you have to ask questions and you have to push for these things as we did. And that's, I think, confusing often to patients because why don't doctors just automatically say we need to get your tumor sequenced and we need to test you for whether there's a genetic underpinning for this?
You'd think that that would happen. And I guess my question is why doesn't it? Why does a patient have to push for it?
Dr. Brian Wolpin: Yeah, I would say less pushing and more just confirming it's getting done, right? So, I think cancer care has become increasingly complicated, right? And even within a disease, breast cancer, lung cancer, others, there are a lot of different ways that those are treated. And I think that as the complexity increases, it's important that patients know for their type of cancer, yes, these are the things that are important. That way they can confirm with their oncologist that they're being done.
So, I think for pancreatic cancer in particular, I think it isn't always as widely understood that it has this inherited component if we use that as an example. And so, I think some oncologists just may not be as aware that that's true, but I think if a patient has sort of been empowered to know that information, then they can confirm that the oncologist understands that that's true and confirm that it gets done in a timely manner, which is important. And I think that's the same with sequencing the tumor, right? These RAS inhibitors, they are so new, right? This is all, I mean, really the FDA approval's just now, right?
We're talking about it right as it's happening. And so there is always some delay for uptake of information more broadly. And so as much as patients can be empowered to know this information early and confirm that these things get done, I think it's just better for everyone.
Alisyn Camerota: That's great. Well, Dr. Wolpin, thank you very much for your time. We know this is a very busy week for you. So, thank you for explaining all of this and it's just wonderful to be able to talk about some good news in a field at a particular cancer that so often doesn't have good news.
So, thanks for sharing all of this.
Dr. Brian Wolpin: Well, thank you. Thank you for having me and thank you to your husband and to you for participating, right? These trials and these advances only happen because patients choose and have faith to participate with us. So, I do thank you for that. That's a very generous thing to do.
Alisyn Camerota: Thanks for saying that. I do feel a tinge of, of course, bittersweet sadness that he isn't around to see all these developments, but I feel very proud that he was part of the vanguard to make this happen. So, thank you for recognizing that.
Dr. Brian Wolpin: Of course.
Alisyn Camerota: Okay. Thank you again, Dr. Wolpin. We want to thank our sponsor, Revolution Medicines. Thanks so much to our listeners for tuning in to this episode of PancChat.
I'm Alisyn Camerota, your host, and I'll see you next time.
Julie Fleshman: Hi, I'm Julie Fleshman, President and CEO of PanCAN. If you or a loved one has been diagnosed with pancreatic cancer, navigating this journey can feel overwhelming, but you don't have to do it alone. You can explore the many resources we have about the KRAS gene mutation, tumor testing, clinical trials, and treatments. You can find PanCAN at pancan.org and Let's Win at letswinpc.org. Together, PanCAN and Let's Win are committed to guiding you through every step of the pancreatic cancer journey, offering support, information, and hope.
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