Healthcare Unfiltered
Healthcare Unfiltered is an honest, raw, timely podcast tackling any and all topics in healthcare that affect stakeholders. Dr. Chadi Nabhan uses his dynamic conversational skills to challenge his guests to address controversial and important topics. He also brings on world renowned experts to discuss clinical advances in medicine.
Healthcare Unfiltered
Episode 287 - RAS in Pancreatic Cancer: The RASolute 302 Study
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Chadi is joined by renowned gastrointestinal oncologists, Tanios S. Bekaii-Saab, MD, of Mayo Clinic, and Shubham Pant, MD, MBBS, of MD Anderson Cancer Center, to discuss the groundbreaking findings from the RASolute 302 trial, recently published in The New England Journal of Medicine and presented to a standing ovation during the plenary session at the 2026 ASCO Annual Meeting. Dr. Pant, a study author, provides an insider's perspective on how RAS inhibition is reshaping the treatment landscape for pancreatic cancer, including where these therapies may fit in the current treatment paradigm and how clinicians should manage their unique toxicity profiles. The conversation also looks ahead to the next generation of studies, including RASolute 303 and RASolute 304, and what these trials could mean for the future of precision medicine in pancreatic cancer.
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It's Healthcare Unfiltered, and it's your host, Chaddy Nabhan. Folks, I appreciate you tuning in to this special episode of Healthcare Unfiltered, where we talk about recent advances in pancreas cancer, focusing on the recent data from the Resolute 302 trial, which was published in the New England Journal of Medicine and was presented at the plenary session at the recent ASCO 2026 meeting, where attendees gave the speaker a standing ovation and celebrated the data that was presented because it was one of the most amazing, fascinating data in pancreas cancer that I have ever witnessed. I've been doing this for a long, long time, and I don't recall a time I was that excited, especially as we are dealing with a disease that is known to be deadly. Certainly, this is not the end. This is the beginning of a new era, in my belief, in pancreas cancer. And to highlight all of this, I've invited two phenomenal luminaries in GI Oncology, Dr. Tony Saab, who is the chair of hematology oncology at Mayo Clinic, and Dr. Shubaum Pant, who is a professor and a director of GI oncology at MD Anderson Cancer Center. Both are known GI oncologists, and Schubam was part of the clinical trial that was presented, which we will be discussing on the show. I think it is important to highlight this particular trial. It's also important to talk about the findings, the results, put those in context of managing the disease, and talk a little bit about the side effects, what we actually need to do to manage these side effects and overcome any possible adverse events that may be generated from treating the disease with the KRS inhibition. So I really appreciate tuning in. This is a phenomenal moment and a fundamental progress in managing patients with pancreas cancer. And I suspect that this will translate into much more impressive data outside of uh pancreas cancer as well. Uh folks, check out my website, chadinavan.com. You'll learn more about my books, The Cancer Journey: Understanding Diagnosis, Treatment, Recovery, and Prevention, and Toxic Exposure, the true story behind the Monsanto Trials and the Search for Justice. And as you know, my third book is coming out on December 1st, 2026. AI and Cancer Care when Machines Meet Modern Medicine. Folks, also subscribe to the show. You can find me on Facebook, YouTube, Twitter, Instagram, and all social media platforms. Provide your opinions, your thoughts about any future episodes, any future guests, any future topics. Without further ado, the amazing doctors Saab and Pant on Healthcare Unfiltered talking rests in pancreatic cancer. Well, folks, I'm really excited today on Healthcare Unfiltered because we've got two luminaries in GI oncology. And uh, we just tipping this actually a couple of weeks after the completion of ASCO 2026. Lots of excitement and pancreas cancer, RAS, and all of that good stuff. So welcome to the show, guys. Thanks, Trinity.
SPEAKER_00Thank you, Charlie. You have one luminary and one sideshow. So that's what it is.
SPEAKER_02One and a half luminaries is pretty good. We'll take that. So uh let's just do a quick intro. Although I'm pretty sure all of my viewers and listeners know you by heart now. But uh uh Shubam, maybe a bit about you, where you practice, and what got you into GI oncology, by the way?
SPEAKER_00So uh yeah, I'm Shubham Pant. I'm a professor of GM medical oncology at MD Anderson in Houston, Texas. And yeah, what got me interested in GA oncology is the other person on the screen here, Tony. Uh I I went into his clinic and I swore I would never do GI, but then you know I I got I got I got pulled back into doing it. He was he was uh it was it was a hard, hard time starting his clinic, but towards the end it actually worked out really okay.
SPEAKER_02He has he has a way of convincing people of doing things his way, you know? That's true, that's true. Tony, how about you?
SPEAKER_01Well, uh so Tony Bikai Sab, uh GI medical oncologist, uh uh at Mayo Clinic in Arizona, a good friend of Shubam and a good friend of yours. Yes, sir.
SPEAKER_02And I'm really, really excited about this.
SPEAKER_01You both have taught me. And you know, one of my biggest prides is actually Shubham.
SPEAKER_00Oh, thank you, Tony.
SPEAKER_01You know, you know what they say is you you only know that you have been a great mentor when your mentee outshines you. Yes, that's that's the man right there.
SPEAKER_02You're you're you're very you're very that's the man right there. Very, very, very humble. Well, I'm really excited uh to talk to you guys. Our we're gonna talk about pancreas cancer, about uh lots of the data that came out at um at ASCO 2026. Our focus, of course, is gonna be the data and so on. But before this, um Shubam, why has progress in pancreas cancer been slower than other solid tumors, in your opinion, over the past decade or so?
SPEAKER_00Yeah, I think even more than the past few decades, right? So pancreatic cancer is notoriously a hard uh hard cancer to treat. So mostly when it's 80%, it's found in stage four. And even in the stage four, it's a very aggressive cancer. It caused a lot of other things like pain, weight loss, cachexia. Patients have a poor performance status. And chemotherapy, unfortunately, has just not been able to make its mark. So we've had like a few months of progress in chemotherapy. It's just that it's a it's a challenging tumor. It's got all this trauma, and then it's got this tumor, you know, it's kind of got this tumor cell. So it's like a shield around the cancer. So it's just been traditionally a really hard nut to crack.
SPEAKER_02And then um, Tony, somehow we started hearing about RAS. I mean, we've heard about RAS for for decades, but it wasn't always associated with pancreas cancer. When did we start understanding the association between that oncogene and pancreas cancer?
SPEAKER_01Well, so RAS is uh, you know, a product oncogene that's been uh you know known for quite a long time. And it's its uh significance was that it was known to be a driver, but it was not one driver that we could target. Yeah, there were significant challenges in trying to target RAS, its conformation, it was difficult to essentially get uh uh uh uh uh essentially to target directly. Uh the the problem uh with pancreas cancer, as you know, as Shum alluded to, is that you know 93% of those tumors are uh uh driven by RAS. So before we started getting these potential agents targeting RAS, we had no idea. Uh uh, you know, we had no way to essentially uh bring pancreas cancer into the world of precision oncology where a lot of other cancers were moving. I remember about 10, 15 years ago, I was given the task of uh, you know, debating uh uh I think it was Jordan Berlin then, and my uh my portion of the debate was uh why we should not uh uh apply genomic uh sequencing uh in pancreas cancer. And it was, well, because it's all driven by RAS and we have nothing to target RAS. So it's it was an easy argument to win then. Although I I didn't believe truly that we I still think that we should, and that even then we should uh do this uh you know as much as as feasible. Now it's universal. But the point of this is that it is there and we never had the capacity to target it until more recently with the 12 C's and on that. Chubam and I, you know, worked on on edegrasib. Uh we were both co- uh co-PIs on a study that ultimately showed one of the first proof of principle, the other was Sotorasib with Strickler, that showed that essentially the 12 C's, which are about zero point, I'd say maybe 0.1% of all uh RAS mutation all RAS mutations, pancreas cancer, maybe 0.5%, uh, were 12 C's that you can actually see those responses. So that was a good proof of principle to start with.
SPEAKER_02So out of all pancreas cancers, uh Shuban, all of them, I mean, is pancreas cancer all of it driven by RAS or are there or like there are other factors involved in the progression and development of the disease?
SPEAKER_00Yeah, yeah, so you're right. So there are multiple factors, you know, there are other uh mutations, obviously tumor suppressor gene, P53, we've got smatroph, we've got other other genes part of it, but RAS, as Tony said, is the main driver. So just as Tony said, about 90, 93 percent of RAS uh is of pancreatic cancer is driven by KRAS mutation, about 7 to 10% is KRAS wild type. So, and that's an important subset because that has about 30 to 40 percent of targetable uh mutations, fusions like NRG1 fusions, uh, and red fusions and some other fusions, and TREC fusions. But again, uh just like Tony alluded to, it's a needle in a haystack. It's 0.1% of pancreatic cancer, maybe to 0.5% of pancreatic cancer, but majority are driven by KRAS. And now the amazing thing is that in pancreatic cancer, it's not enough to know KRAS. You have to know those alleles of RAS. That means there's KRAS G12D is 40%, KRAS G12V is 30%, KRAS G12R is 15%. And why these are important is because we have a number of agents now which are showing activity for let's say KRS G12D. So we have, you know, you know, about 10 agents, about three, four of them could be going, three of them have already gone into four phase three clinical trials in pancreatic cancer and more are coming. And we have a KRS G12V agent also coming out. So it's now not enough to know that it is really RAS mutant. Now we need to know what allele are we targeting in in KRAS, which is very important also.
SPEAKER_02Tony, for the community oncologists, how do they usually get the RAS test? If a community oncologist is seeing a piropancreas cancer and the biopsy is sent, does the report automatically tell them what it is? Do they have to ask what happens in the community setting?
SPEAKER_01Well, I mean, you know, I think like with every uh every cancer we treat, uh now you need to know your tumor. Uh I mean, you always have to know your tumor. As Shubam alluded to, is it's not just RAS, but it's also in the RAS-wild type, you have a number of elements that have agents uh that match to it. Now, most of these, if not all of these, for now, are in second line and beyond. Ultimately, they're gonna move to first line, it's my bet, at least the RAS inhibitors. So, Shubum and I are part of a lot of these studies that are moving uh, you know, a lot of these RAS targeted strategies in the first line. So uh testing, you know, is two ways liquid and tissue. Uh, we tend to do both uh at the same time. Liquid comes fast, uh, seven days, eight days, tissue takes a little bit longer. Tissue is the golden standard. Uh, a lot of the fusions can be missed uh by liquid, and so you do want tissue. Uh, but also uh, well, for metastatic pancreas cancer, although the shedding rate is a little bit lower uh than say colon cancer or others, but with metastatic disease, especially involving the liver, or you get tricky if it's the lungs or the the uh uh the peritoneal cavity, but the liver, which is 80 plus percent of the patients, you're gonna see actually uh circulating tumor DNA. And this is how you're gonna capture RAS, not only RAS mutations, but the essentially what allele of RAS is mutated, so V, D, C or others.
SPEAKER_02So, Shubam, with this background, so much attention about the RASOLUTE trial that was uh presented at the plenary session, published in the New Nodor Mass. And take us through at least um the rationale and what did patients receive?
SPEAKER_00Yeah, so this was the called the Rasolute 302 trial. The drug is called Duraxxon RASIB. Still, I think we'll all have to get used to pronouncing it properly. Uh, everybody's gets get Diracon, Duraxon. So I call it Diraxon for short. So this trial was based on a phase one trial. So we did this phase one trial. So Diraxon RASIB is essentially like a molecular glue. So think about it, it binds to RAS on. So as we've talked about, that RAS, uh KRAS is mostly in the switch-on stage. So think about it like a light switch. It's turned on and stuck in the on position, giving the cell signal to grow. And this drug is a molecular glue, binds to a cell of chaperon called cyclofilin A, and which binds to the RAS-on protein and flips that switch off. So it turns it from on to off, right? And that's really important. That's the unique thing about this drug. Like Tony was talking about, adagrasive, sotorassive bind to the off position, which is a little bit easier than, you know, then kind of getting to this on position. So that's the unique thing about this drug. It's a RAS-on inhibitor. And this trial was we did the phase one trial in which we saw a response rate of 33%, uh, progression, free survival of about seven plus months in this patient population, which was pre-treated with chemotherapy. So this formed the basis of the Rasli 302 trial. It was for patients who've been pre-treated with one uh regimen already. So it could be 5 FU-based or gem xytopine-based. And if they progressed on it, then they got randomized to either Duraxxon RACIB as a pill, which was unheard of in pancreatic cancer. You know, before Tony said before adagrasib was and sortoracib are the first kind of proof of principle. So patients got randomized to duraxon RACIB versus a chemotherapy, and it could be any chemotherapy. So if uh if they got gem cytobin pretreated, you could treat them with a 5FU-based regimen. If it was 5FU based, you could treat with a gem citabin-based regimen. So very open trial, like really this is how, this is how it's practiced, right? This is how pancreatic cancer is practiced in the community. And what we saw was um that there was a doubling of survival in patients who received Duraxon RACIP. So it was chemotherapy, interestingly, in this chemotherapy arm did not underperform. So six months survival is very standard for most chemotherapies across multiple trials. Tony have done, you know, a few positive trials, but mostly negative trials, which kind of show you that six month kind of thing. But it really Dirac on RACIB, like double the survival. And I'll tell you one other thing which was unique, Jadi, is when we did the phase one trial, any trial that you look at, for I would say at least in pancreatic cancer, when we do the phase one, there's an acute drop-off in the progression pre-survival, response rate, overall survival in the phase three trial. So we expected this drop-off, but it was just unique that the results that we saw with the phase one trial, they are almost superimposed into the results of the phase three trials. That survival of 13.2 months, progression-free survival of 7.5 months, response rate of 33%. And it was just a truly remarkable, you know, remarkable kind of results, honestly, for folks like us who've been treating with pancreatic cancer.
SPEAKER_02Shubam, folks who progressed on chemotherapy, did they cross over?
SPEAKER_00No, no. So they the ones that this was there was no crossover allowed on the trial. Uh, the crossover as now allowed on the trial, uh, because now the trial kind of read out its primary endpoint.
SPEAKER_02So, Tony, your reaction to this specifically, the um has ratio, the difference of this. And I do recall me and you had a conversation when we met at ASCO, you commented on the how this may be changing the biology of disease based on the separation of the curves. Can you comment on that a little bit?
SPEAKER_01Yeah, I mean the hazard ratio is solid. Uh 0.4. It's something that you don't see in pancreas cancer. It's something you rarely see in any cancer, but lo and behold, in pancreas cancer. And what that tells you, if you look at the at the curves and you look at the points, is every single almost every single patient who's receiving their axon RASAP is benefiting from the drug. That's point one number one. The other point is that that separation happens in the first month or two of treatment. Survival. We're talking about survival, not BFS or or others, you know, where you have a response or not. This is people essentially benefiting with a survival outcome. And uh that curve continues to be superior and widens as you go with time. I mean, you hit the one-year mark, okay? The one-year mark, second line pancreas cancer. More than half of the patients in the second line were still alive versus less than 20% in uh chemo. And then it with chemo, you're gonna continue to see this drop. The interesting part is that with the raxon, you start seeing a little bit of flattening around that time. We'll see, you know, where it goes with further follow-up. But the fact that essentially uh your uh uh your your curves look wide as widely separated and early on tells me that, and that's very similar to what we've seen with BRAF V600E mutated colorectal cancers and anchor raffidive and cetoximab, that separation, that very wide separation, that tells me that you're changing the biology of the of the cancer, meaning you're you're moving it from an aggressive to a less aggressive form of tumor. You're probably manipulating the microenvironment. We know that essentially targeting RAS creates a more favorable immune milieu, uh, which is more conducive essentially for uh the cancer uh to behave a little bit better. That also allows patients to be more performant as they move to their next line of therapy. So it's not just benefiting them during this line of therapy, but it's also opens the way for more lines of therapy. You're really changing the biology of the cancer. And I think that's remarkable. And that tells you the whole story there. Uh 60% reduction in the risk of death is is pretty darn significant. Now, if you look at the p-value, I mean, you you you can't count the zeros before you get to the to the to the actual uh you know number. And that again tells you, I mean, this is not just significant, this is incredibly significant. It's almost like SpaceX significant in the number of zeros before.
SPEAKER_02Shalom, you you uh at MD Anderson, you participated in this in the trial and you you've enrolled on it and and and and all of that. What can you comment a bit on the side effects and toxicities? And I asked this because I mean, we heard a lot about the toxicities from um uh Ben Sassy, the uh I think, you know, uh the politician who was diagnosed with the disease and received the treatment and so on. So all we hear about the rash and so on. Spend some time just explaining to us what patients what should patients expect in terms of side effects, and then we can talk about how best to manage that.
SPEAKER_00Yeah, so I think side effects, you know, are there like with any other therapy. So rash is one of the main side effects. About 90% of patients will get rash, and about 15% of patients will get up grade three rash. So it'll be, you know, where you have to hold the drug and potentially dose reduce. So what happens is, but like with anything, honestly, Charlie, I don't know if you remember the good old days of Cetoximab when it came out and like people are getting this rash. And when capsidopin came out, honestly, and you know, the hand foot syndrome was coming out and the dosing of capsitabine, you know, so all this, I think what happens in oncology communities, we get around to figuring out how to make this more tolerable for patients, uh, whether it's for dose holds or with dose reductions. Chody, uh, sorry, uh Tony ran a great study with Roger Rafenev, you know, at the uh the Rido study, which was really like informs how clinic is, you know, how we run our clinic. So I think a lot of that is coming to, but to answer your question, rash is there are side effects with rash. You're inhibiting the MAP kinase pathway that's important for the skin. The other thing is it becomes pro-inflammatory. So there is, we're trying to tamp down the inflammation because the skin becomes a, you know, there's inflammation leading to this rash essentially. So we give doxycycline essentially for every patient who's starting off, and it's more for it's prophylactic for the inflammation, essentially. So I've, you know, I've had discussions with our uh dermatologists, and a dermatologist have managed a lot of patients with uh rash. So we start them on doxycycline as prophylaxis and hydrocortisone 2.5% cream uh for the face. And that seems to at least get us on a good path to start the patients. Now, if they get a rash, um uh we have to sometimes it gets super infected. So sometimes they need antibiotics. Uh we have to hold the drug sometimes and dose adjust to a lower dose. And you know, uh that you know that has to be done with the patients who are getting this intolerable grade two rash or grade three rash. Remember, it's not only the grade three. Right. But if you get an intolerable grade two rash, you know, for a longer period, that's also significant. But I think what we've gotten from the beginning, because you know, having treat patients on this for for a good amount of time, I think we come, we've come a long way uh to trying to improve the outcomes for the patients. But there are patients, obviously, that you'll have to stop and dose adjust those patients uh, you know, who come with the rash. Uh at Anderson, you know, we have access to dermatologists who are very good at this. So sometimes patients need to go on Accutane. That's what they use sometimes. There's some data, there's some like talk about cyclosporin cream in some areas that seems to, in some patients, that seems to do better. But I think, you know, it's all trial and error right now. I think there are different trials which are ongoing that I think we'll be able to figure out a good skin regimen. And if the patients who cannot tolerate it, they might have to hold. And normally we've seen once you hold the drug, in one to two weeks it gets better. And then we can, you know, restart the patients either the same dose or with a dose adjustment.
SPEAKER_02Did you say everybody starts with doxycycline, or you said do we use that in case we need it? Do you say that?
SPEAKER_00No, we do that prophylactically. So if uh your community on colleges starting on the EAP or who are starting on, you know, well, Dirac and RASIV and we all expect it to get approved sometime, then we would uh we would uh I would encourage them to start it prophylactically from day one.
SPEAKER_02And they stay on doxycycline?
SPEAKER_00Well, it depends. Now, if they if they uh you know are on for a couple of months and they don't get a rash or they get a grade one rash tolerable, then they can get off it. So again, this is all a TBD in production, basically. I think it'll be in the hands of the individual provider on how to manage these things, but these are the broad guidelines, which I think will come out by the time uh you know by the time this drug is ready for you know truly prime time for for everyone.
SPEAKER_01Yeah, I'll make a little pitch. I I I agree with the prophylactic piece. I would I would advocate though for using aminocycline instead of doxycycline. Uh and the main reason for this is doxycycline retains antibiotic properties. And I've had a couple of patients who actually developed C. diff, believe it or not. I was gonna ask that. Uh uh, you know, with doxycycline. Minocycline historically was being developed as a less toxic doxycycline. But then then found out that it has zero antibiotic potential, but it remains an anti-inflammatory. And that's one of the reasons why it works. So if you look at the history of developing mostly doxycycline and aminocycline, doxycycline has a little bit more data with the EGFR inhibitors. There's one study with aminocycline uh that showed you know similar results, although it was a single-arm study. So I've actually moved my practice. I'm not saying doxycycline is wrong. I just say you know that uh after I've seen a couple of the patients, you know, with issues with doxycycline, uh, I became more convinced that uh, you know, I'm gonna rely mostly on aminocycline. Now, the question is is as you know, Schubam alluded to is, you know, do you keep them for more than two months? Uh the answer is you may not need to, because all these studies actually have six to eight weeks with EGFR inhibitors. That said, I will tell you that in common practice, uh, for the busy oncologist, most of the time you're not gonna even remember uh to check that point, and patient will continue to take them. And it's okay. I've had a lot of patients who were on aminocycline for a year plus with almost no toxicities.
SPEAKER_00But Charlie, this tells you, I just want to intervene, this tells you something about about things. Tony told me something today that, you know, that's that's kind of new to me. You know what I'm saying? That we've used, at least in the trial and for everything, we've used doxycycline. But maybe we'll switch to using monocycline. You know, so the thing is, I think once the drug gets out there in our hands, I think everybody's gonna adapt, learn from each other, and really learn how to do that.
SPEAKER_02That's a pitch, that's a pitch for real-world evidence, which I'm a big proponent of, by the way. Right.
SPEAKER_01But you know, you but you know, Shubaum has one of the largest uh experiences with Denax on Rasiv. Uh so I think he single-handedly probably knows more than anyone else how to handle the rash. And that's that's that's what we have him on.
SPEAKER_02But one of the one of the things you mentioned actually, Shubam, uh, is that despite how ugly looking the rash looks and how aggressive it appears, patients actually are feeling better clinically. Like they actually, you you told me once you struggled in trying to withhold the drug for some of the patients.
SPEAKER_00Yes, I had a patient with a grade three rash, superinfected, and I was, you know, it was like a, I would say a half an hour, hour long clinic visit in which we were going back and forth and you know, about this, because the thing is the patient felt better. So what happens is even if we look at the trial which was presented, the PROs got better. So patients felt better. And why is that, you know, going back to the gem cytomine days, right? There's clinical benefit because pancreatic cancer is such a terrible disease because patients feel bad. There's a lot of pain associated with it, they're losing weight. So what happens is once you control the disease, and I've seen dramatic falls in CN99 with this drug, like in two weeks. I I on another trial, I saw a patient, I don't know how they measured it. I had a patient I was showing my team the other day, had a CN99 of 672,000. I don't even know who measured it. I didn't know if my buttons they could even measure that, but normally greater than 100,000, you know, normally it's not measured. But for whatever reason, the pathologist had measured the CN99 of 672,000. And now this patient has a CN99 of 172. That is crazy in my in my this thing. I was showing them the graph. Like I had to like show that go up to like 672,000. But what I'm saying is so that patients feel better because they're eating more, they're having less pain. I had a patient who was um, and I tell the story, who's who's a big golfer. So before he came and was a big golfer, and he was just like, it was a quality of life thing for him. He just, that was his stress relief. He used to give God, and then he couldn't because he was in so much pain, he was just laid up. And like within a month, he was like out there golfing. And obviously, we had to tell him about sun exposure. That's the other thing. Big thing on this drug is that you have to use sunscreen. And uh with our dermatologists, when we talk to them, it's actually mineral-based sunscreens. You don't ask me which ones they are, but it's mineral-based sunscreens that are out there because they kind of stay a little bit longer and they're a little bit more effective than regular sunscreens out there. So sunscreen is very, very important. We have to educate our patients on sun exposure because they're they get exquisitely sensitive to sun. So we tell them, you know, full sleeves, you know, wear rash guards, you know, wear a hat, be careful. So that's important for patients to understand also that sun exposure is a big, is a big factor in this drug, also.
SPEAKER_02Tony, as we're expecting the approval of this drug anytime in the next few weeks, what should community oncologists who are general community oncologists watch for in the first few weeks as they start using the drug? Any cheat sheets, like things that you want to alert them to watch for as they start using the drug?
SPEAKER_01Yeah, no, I I think you've heard quite a bit about, you know, prevention, uh, preemption, uh, you know, starting prophylactic uh management. You also heard about, and I think that's important because we, you know, remember the days of EGFR inhibitors and how it fell out of favor because people didn't know how to uh essentially uh work through the preventive measures. Preemptive instead of reactive is key because you lessen quite a bit the grade of toxicity. Uh but you also heard, you know, from from Schubam and from you know results of the study that the PRO has showed improvement. And we know that. I mean, we for for folks who treat a lot of pancreas cancer patients, the turnaround is amazing. I mean, those are patients just lose a lot of weight, muscle weight, strength, pain. Uh, and then, you know, they turn around, but they have the rash, but everything else feels great. So the and the rash is manageable. Yeah, you just have to know how to prevent it and how to take care of it. Setting the expectation with the patient is key. Setting the expectation with the oncologist is key as well. And with the staff. Many times those patients are not technically seen by the oncologist. They see the oncologist and then they see them when they have their scans. So, you know, we have to educate essentially the nurse practitioners, the nurses, the pharmacists, everyone needs to understand that yes, the rash will develop in most patients, and for few, uh, you know, a significant number of a few, you know, you're gonna have a significant rash that's manageable. You just need to know that overall survival is significantly better. So you're helping the patients live way longer. Remember, half of them are you know cross more than half across the one-year line in the second line. And then uh uh they feel better overall, and that's not insignificant. One thing that concerns me a little bit is you what happens is when uh an agent with a lot of hype around it, and this deserves the hype, by the way, gets approved, you know, every patient with performed status 3-4, failed multiple lines of therapy, will ultimately be considered for this agent. Now, that doesn't mean you shouldn't, if it makes sense, but this is where you have to be careful. Those patients may experience more toxicities, these patients may be less likely to do as well with the treatment. So we have to be careful. And the first experience can be a tough, a tougher experience than ultimately when you get used to the drug. But the first experience is gonna be with those patients who have failed multiple other lines of therapy. So we have to essentially, you know, uh uh understand that ultimately uh uh as we uh uh you know have this agent available to us, its best place is in the second line for now, until uh we have trials in the first line that are uh that are ongoing or about to start uh to hopefully take you to the first line.
SPEAKER_02Yeah, I was gonna actually, I know we have just a few more minutes, but I was gonna ask uh Shuban now after the Resolute 302 study the algorithm of managing pancreas cancer, how did it change now for uh the community oncologist?
SPEAKER_00Yeah, so I think uh, Jari, this is the Rasolute 302. I think it's very uh so the second line patients, exactly as Tony said. Um I think it'll supplant chemotherapy, rightly so, for the appropriate patients, uh, for the second line, uh, for the second line standard of care. Uh but again, as Tony said, you know, you just everybody needs to get used to the drug. So don't let your first impression be the last impression. Sometimes, you know, you you will see the side effects and everything if we know how to manage it. Um I think that's the most important thing because you keep the patients on, they do get that benefit of pain control and they're eating better. And as Tony said, they kind of get their quality of life really, really improves. But you know, we're not, I think in pancreating cancer now, we've tasted blood, right? We're just getting started now. So we are moving into the frontline step.
SPEAKER_02What are the next steps? Yeah. What are the next steps?
SPEAKER_00The next steps are RASLIC303, which is uh which is a trial, global trial, which has which we're starting with Duraxxon RACIP or Duraxon RASIP is with Gemnapaclitaxel or Gemnapaclitaxel in the three arms. I mean, think about it. If if we talked about giving a pill for frontline pancreatic cancer two, three years back, it would have been unheard of. But here we are with, and we've seen some responses already, up to 50% in a smaller phase one cohort, right? So there is some data there. So that's the RASLID 303. We also have the RASLI 304, which is which is in the adjuvant setting. So after resection, after uh chemotherapy, patients can get randomized one-on-one to either Duraxon RASIB or uh watchful waiting, like we normally do with these patients. And then we have, we didn't talk about the KRS G12Ds because we don't have so much time, but there's RASL305 and RASLID 309. In 305, you're combining uh Zoldon RASIB with chemotherapy, gemabraxin or fulfillinox. And RASLID309, I think, which is one of the most exciting trials, which is going to come out, is a novel novel combining Diraxon RASIB with Zoldon RASIB, PAN RAS with a KRAS G2D versus chemotherapy. So I'm really excited about that trial for the potential to really improve the uh outcomes for our patients with K Ras G12.
SPEAKER_02This reminds me, like 20 years ago, the catalyst event that happened in lung cancer was the EGFR, right? I mean, I think we all remember, and you know, since then it has changed drastically. And I think I think this is what's happening. I don't recall the outstanding ovation that we saw at ASCO. Um, I don't know. I I got goosebumps when you saw that.
SPEAKER_01Well, that's the reason why you call this the RAS revolution, because it finally took us away from just being uh slaves to chemotherapy. Now, that doesn't mean chemotherapy is going away completely, yeah, but it may actually be replaced in the earlier lines, as Shumab said with all these studies by uh, you know, an oral agent or uh, you know, two oral agents put together. I mean, there are certainly a lot of hints uh with uh a lot of these agents about significant single agent activities. There are also other platforms that are developing their RAS inhibitors, you know, there's an inside compound, also 12D, that's being developed with chemotherapy. There is uh ProTac, a degrader, uh, which frankly, you know, I hold my judgment on this. I think the mechanism of action is a bit more problematic. There's also uh, you know, novel mech inhibitors that are being developed. There is other mechanistic drugs, but I think, frankly, all these are ultimately going to be um, you know, interesting, uh, may become parts of our standard. But the platform we're seeing right now with their axon, uh, at this point at least, you know, and looking at a lot of different uh agents in development, this one blows everything off the water, right? Wouldn't you agree, Shuba?
SPEAKER_00Absolutely. I think it's just the it's the way I see it, Charlie. I show this one slide about the about exactly cracking KRAS. So I show this dam, which is like bursting in different places. And that's the way I look at it. Like we've blown up one part of the dam, and then you know, all these drugs are coming to kind of attack the cancer cells, and then we're going to towards the other side. And, you know, and so I'm really, I'm really excited for the future. Lots of lots of work to do, lots of interesting trials. And as Tony was saying, RAS might change the immune milieu of the tumor. So maybe that you could bring in immunotherapy. We've tried immunotherapy for two decades in pancreas, hasn't worked because it's such an immune desert. But maybe we have a chance now of uh of maybe combining with immunotherapy, making the response more durable. So, you know, maybe 13 months is not good enough for us anymore. We want to go the long way. Like put it, you know, get get get it longer.
SPEAKER_02The oncology community has been so frustrated with pancreas cancer that when we saw these curves on the screen, I mean, it was it was really genuine an emotional moment with all of us just you know uh celebrating this. So kudos to you guys leading the the field and making a huge difference in patients' lives. And um, anything I should have covered or asked you about RAS, pancreas cancer resolute that I completely forgot and we should really let people know about.
SPEAKER_00I think you covered everything, yeah.
SPEAKER_01I think it was uh it was a good thing. The future is bright for our patients. That's all what I have to say.
SPEAKER_02Dr. Shuban Pant and uh Dr. Tanyos Bikaisa from MD Anderson Mayo Clinic, respectively. Thank you so much for joining me on Healthcare and Filtered.
SPEAKER_00Thank you.
SPEAKER_01Thanks, Shadi.
SPEAKER_02Okay, folks, thank you so much. This has been absolutely amazing, and I cannot thank my guests enough. Uh, this is exciting. Please share your thoughts and let me know what you think about this podcast episode and other podcast episodes. You can subscribe to the show. And this is like almost seven years now doing healthcare unfiltered. Um, thousands of listeners, hundreds of guests, and I really could not have done it without you folks who tune in every Tuesday, week in, and week out. Before I let you go, I'm gonna leave you with a saying by Winston Churchill. We make a living by what we get, but we make a life by what we give. Until next time, take care.