Educated Patient®: An Insightful Look at GIST and Available Treatment Options



Ryan McDonald: Hello everyone and welcome to today's live broadcast, an Educated Patient Webinar – An Insightful Look at GIST and Available Treatment Options. I'm Ryan McDonald, associate editorial director of CURE. We are pleased to bring you this webcast presented by CURE and our partner GIST Support International. There are just a few important announcements before we begin. We encourage you to ask questions during the event, which you can submit by typing them in the Q&A box you see on your screen. You will be receiving a survey via email tomorrow, and as a thank you for watching the full webinar and completing the survey, you will be entered for a chance to win of Visa gift card. Now let's welcome our panelists for today's webinar. Dr. Gina D'Amato, an associate professor of medicine, Sarcoma Medical Oncology, and assistant director of clinical research at Sylvester Comprehensive Cancer Center in the University of Miami Health System. Sandra Brackert, a nurse practitioner within the UCLA Sarcoma Program, and Marina Symcox, manager, board of directors, GIST Support International. Now I'd like to kick us off on today's webinar, talking about the basics of GIST and finding the right team. Dr. D'Amato, I'd like to start with you. Before we dive kind of more into the specifics about finding a treatment team, can you please provide a brief overview of what GIST is?

Gina D'Amato: GIST is a type of sarcoma. It's a cancer that starts out from the connective tissue cells of the GI tract. In general, cancers could start out anywhere in your body. If they start out from connective tissue, they're called sarcomas and there's many different kinds of sarcomas, over 170 different types, and GIST is the most common type, about 5,000 new cases every year in the United States although we think it's probably underreported. You have your GI tract, which makes your esophagus, stomach, small intestine, large intestine, and you have the inside lining of the intestine that if you get cancer from the inside lining, that's a carcinoma so gastric carcinoma, colon carcinoma. If it starts out from the muscle layer, then it's a GIST and those cells that are responsible for moving the food down the GI tract, those are the cells that mutate and turn into sarcoma and turn into GIST. The most common location that it starts out from is the stomach, but it could also start out anywhere. The second most common is from the small intestine, then large intestine, esophagus. The cure is surgery, but about 50% [00:03:00] of the time it could come back and if it comes back, it could spread to various areas. Luckily, we have lots of new treatments available for it so of course we'll be going into to that in more detail, but that's the gist of GIST. I'm sorry. There's too many puns to be involved with GIST.

Ryan McDonald: No worries. Sandra, as Dr. D'Amato was kind of alluding to, there's belief this may be underreported, but it's a relatively rare disease. Why is it important that our attendees and patients out there see a specialist or a team that just specializes in the specific treatment of this disease?

Sandra Brackert: Well, I think you said it right there. It's a rare diagnosis and so I think anytime anyone has a rare diagnosis such as GIST, it's all the more important to see a specialist because most general even oncologist do ever see a case. Sometimes just because they do occur in the GI tract, sometimes people go and see a gastroenterologist or a GI oncologist. At UCLA, we have a sarcoma team so just as our specialty, but it is important to see a doctor that sees these patients regularly. I took little notes just so I wouldn't forget to say some specific reasons why. The main thing is once you have the diagnosis, you need a thorough workup, and you need someone that specializes in this disease to even know how to go about doing a thorough workup. The specialist doctor will do a physical exam and blood work. They do imaging to make sure that you just have maybe a primary site, or if there's any other sites of disease. They'll order tissue sampling to do a mutation analysis. They'll talk to you about the special treatment for GIST which does take some expertise in knowing what treatments to recommend. It's not just the treatment that they recommend, but how long should you stay on that treatment. Even if you do need a treatment, some smaller GIST, some lower risk GIST may not even need to be treated. Surgery may be all you need. These are very specific questions that need to be answered. Each case is different, so you want to go to someone that has seen a lot of cases and know exactly what they're dealing with and when to start treatment. Do we start treatment before surgery? Like I said, how long do you continue the treatment for? When is it time to [00:06:00] change treatment? How often do we monitor people on treatment? How do we manage the side effects of treatment? Seeing how people tolerate it. Then when you go to these specialized clinics, if you're on a treatment that stops working and we need to find new treatments out there, these are the clinics that are aware of new treatments, maybe clinical trials, et cetera. I think those are a few of the good reasons, main reasons. It's so important to see someone that specializes in GIST.

Ryan McDonald: As we're talking about this and Marina, Sandra talked about all these different options and how do you decide on which treatment and when and making all those decisions. With your advice, how do you give patients kind of advice on how to make those decisions and what they should consider when they're in that situation?

Marina Simcox: Oh, me?

Ryan McDonald: Yes.

Marina Symcox: I was diagnosed in the 1990s with metastatic disease, so I come from it from a different point of view, just wasn't yet a diagnosis and there were no TKI treatments at the time. For myself, I've always had two tiers in healthcare. I've had a good local team and I've also had my specialty center. I was in the original Gleevec trial from 2000, I'm still in that trial, so I have my specialty team and I have my local team. For myself, I find that the most important thing for a patient is to have a local doctor's office that's very responsive. It may be your oncologist, but it might be your general practitioner. I have found, I've been dealing with GIST now for 25 years, that my local family doctor was actually the most responsive. He learned with me as the science changed into what it is today but if I need something that I can't get solved by myself, he will place those phone calls for me. I also think patients need to, if you are not able to go to a specialty center, you can definitely know where the shortlist is of places you want to go where the closest major sarcoma center is next to you. You may be able to get a one-time consultation and that will open the door so that your local physicians can consult with the specialist.

Ryan McDonald: Kind of follow-up there Marina as you talk about you can either have a [00:09:00] team of local and specialists and everything. You mentioned your primary care provider was probably one of your best responsive advocates. Speaking of advocacy, how can patients’ kind of be their own best advocate when they're going through this and if people aren't necessarily listening to them?

Marina Symcox: Well, for myself, when I was diagnosed in the nineties, I joined a sarcoma patient forum and that became the grapevine and the conduit of all information for me. It does come with the usual caveats of its social media, but the conversations, this is where I learned where the latest trial was, is where I developed my short list of sarcoma centers that I would want to be a patient at. Self-education is very important. You do need to learn how to use the internet and go to reliable sites such as sites that are by hospitals or the government or major medical organizations. Those are your most reliable. Patient groups I would view them more as a conversation. The conversation is very valuable, but it's not necessarily a hundred percent reliable either. It can be a valuable grapevine to get some information that you need. Someone there may know of a trial that your local doctor does not know about. That's what happened to me.

Ryan McDonald: Dr. D'Amato, as we've kind of been going through so far just the basics or getting the gist of GIST, as you mentioned, and kind of getting all this information, we've talked about the role nurses play, the role maybe a surgical oncologist plays and all types of things. How much of a role does this multidisciplinary approach play in the treatment of this disease?

Gina D'Amato: It's extremely important that you have one cancer, but you have multiple doctors to help you with that cancer. You have your medical oncologist if it's a metastatic disease, for example, you have your medical oncologist but a lot of times we're seeing how the tumors are responding to treatment and so we need specialized radiologists because later when we talk about treatments, the treatments sometimes they can liquefy the tumors. A lot of times they liquefy the tumors, and they can even get bigger initially and then they get smaller, or they stay the same size but they're not becoming liquified. That's important to understand how the treatments are working. [00:12:00] If you have a radiologist that specializes in GIST, as part of the sarcoma GIST team, they can understand those nuances. Pathologist is very important to recognize GIST. Sometimes other cancers can mimic GIST and it can mimic other types of sarcomas like lio mio sarcoma before we understood the nuances of testing for the kit protein, just where it used to be called lio mio sarcoma. Then really understanding the necessity to say if it was a newly diagnosed tumor that was resected out, the size of the tumor, the mitotic index which is how many cells growing under the microscope, all those are important for the other doctors to make treatment decisions on additional treatment. We have the radiologist, we have the pathologist, we have the surgical oncologist, of course, because to remove the primary tumor, or sometimes we do what's called [INAUDIBLE] where we remove a couple of liver lesions or lesions that even though it's spread, they do surgery. We have multidisciplinary tumor boards where we discuss the cases, and we have everyone's input. Is the current treatment working? Yes. Should we go for surgery? What does the surgical oncologist think? What do the radiologist think? Also, specialized gastroenterologist. We have a regular gastroenterologist that does endoscopies and colonoscopies, but they can only see tumors that are on the inside, but again, these are on the outside so if we have to do special biopsies or try to figure out, is it involved in the liver, they can get a procedure called an endoscopic ultrasound, and that's done by a specialized gastroenterologist, an interventional gastroenterologist. If they're part of the team, they're used to seeing the GIST patients. Every once in a while, we do give radiation. These tumors are sensitive to radiation so sometimes we offer radiation, not all the cases, but occasionally, and that's a radiation oncologist. Multidisciplinary when we're making decisions is extremely important.

Ryan McDonald: Thank you. Before we go on to the next question, I just want to remind everybody out there, if you have any questions, please submit them for our panelists on the Q&A box on your screen. We will be doing a Q&A session at the tail end of this webinar. Moving on, I'd like to kind of talk a little bit about genetic testing. You hear of genetic testing, and a lot of times you hear of some of the more primary, well-known, talked about cancers like breast cancer, but it is something that happens [00:15:00] in GIST as well. Sandra, can you talk about genetic testing and why it is important that patients undergo mutational and ctDNA testing?

Sandra Brackert: Yeah. GIST is actually one of the very first discovered mutation-driven cancers, and this has become a much more mainstream process is to undergo genetic sequencing of the tumors to see what kind of mutation they have, and most GISTs are positive mutations in the KIT or the PDGFRA protein. Then there's specific mutations from there and most probably are what we call Exon11. And then maybe 70% or so are Exon11 mutations followed by an Exon9 mutation which may be, I don't know, 12% to 15%, and then there's other more rarer mutations like in 13, 14, 17, 18 that may make up a few percent of cases. I think we'll talk more later about if the primary tumor starts out as Exon9 or 11 and then they develop further mutations. Then the rarer mutations start popping up. There's also, if it's not a KIT or a PGGFRA mutation there's other very rare types of wild type if it doesn't have either or there are some genetically linked, you'll see it more in younger adults where they have SDH deficiency or neurofibromatosis 1 diagnosis. It is important for us to see what kind of mutation is there and it will guide the treatment somewhat. We'll talk about that more later as well. The circulating DNA is also something we look at. You need to have enough DNA circulating in the bloodstream in order to have that show up so that may not always show up, but we always make sure that at the time of the biopsy or the time of the resection that we send off some tissue to undergo the genetic sequencing to see what kind of mutation [00:18:00] is there.

Ryan McDonald: Dr. D'Amato, Sandra kind of alluded to it that some of these results may inform treatment decisions. Can you walk us through a little bit of how these results may inform said treatment decisions?

Gina D'Amato: As Sandra said, the tumors can start out from different gene mutations that code for proteins that cause the cells to be abnormal and grow. The most common gene mutated is KIT gene in 80% but we have other gene mutations. Based on where in the gene it's mutated, then we can predict how a treatment is going to work. As Sandra said, the most common area in the KIT gene that's mutated is Exon11. That happens around 80%. Those are the patients that will respond very well to imatinib, for example. If you have a different mutation in another location of the KIT gene say an Exon9 mutation, then regular dose imatinib wouldn't be effective. We would double the dose and then it can be effective, or we try different treatments. That's based on the primary, the original tumor that we biopsy and we send it out for special molecular testing, the gene profiling. Now, this is different. There's difference between checking the genes on the tumor versus hereditary genes if these genes were passed on from your parents. Other genes that make you susceptible to cancer like BRCA genes and P53 genes, these are different hereditary genes than the KIT gene. The KIT gene most likely would not have been passed on, but sometimes we find that the tumors don't have KIT genes. They used to be called wild type, but now that we can send for special molecular testing, they may have a SDH gene or NF1, as Sandra said, and those can be hereditary so we would want to send those patients to the genetic counselor. If they had those kinds of mutations, the standard therapies aren't effective, but we have several clinical trials that they can be eligible for looking at different types of treatment. It's really important that we really understand there is one rare mutation of the PDGF alpha called the D842V, for example, and there's a drug avapritinib for that. We really want to know first, what the primary is, and we would only need to do it if we need to treat with medicine. If we don't need to treat, if it was a small GIST that was just removed, we don't think it's going to come back, [00:21:00] we don't need to test for it, but if it was something that we really need to treat, we want to get that. Now, the ctDNA is not used as frequently as just testing the primary because it's just starting to come. We learned a lot this year at ASCO last month. We had big presentations about ctDNA, and we can detect these mutations in the blood in between say you are on a treatment and the scans are showing it's not working, and we need to switch the treatment. We can see, did the patient develop resistant mutations? If so, then we can tailor the treatment based on those resistant mutations. It's not mainstream yet, but a lot of the sarcoma centers are doing it and we're really trying to alter what we do outside of a clinical trial. Our group at Sylvester had presented data that was similar to the other presentation, where we saw that if we tailored our treatment based on the ctDNA, we had better outcomes.

Ryan McDonald: Now you were talking about genetic testing and all of these moving parts. I know personally for me, and I'm sure everybody out there, this can be a very confusing topic. There's a lot going on. Marina, you mentioned your case diagnosed in the 1990s. I'm assuming genetic testing wasn't a thing back then unless you can kind of inform me otherwise.

Marina Symcox: Yes. Not only genetic testing wasn't a thing, KIT-staining wasn't a thing either so I had lio mio sarcoma for a while. I was five years into my diagnosis before I learned that my mutation was in the KIT gene. I had been on Gleevec for two years. It's part of the trial because initially we weren't told what our mutation was because that information was done in a research lab. There are certain regulations and procedures about what can be shared with patients and what can't. Clinical laboratory testing that could be shared with patients really came a bit later. I did find out that I had a very common Exon11 point mutation, and it has been highly sensitive to Gleevec. I think we almost knew that was going to be the case because I'd been on Gleevec for a long time before I ever had that results. A shout out to Dr. Corless at OHSU because he surprised me and went and got my mutation done for me in their newly opened clinical laboratory for sequencing way back, 2002, 2003. I had not known when it [00:24:00] was and patients in the trial had been frustrated that we weren't able to be told, although it was explained why. He surprised me one day with that answer in an email. That's how I found out. I do think if a patient wanders onto a patient forum online, they will introduce themselves. One of the first things will happen is they'll be inundated with comments of get to a specialist and get mutational testing. I think the information is out there so take heart in that.

Ryan McDonald: Thank you. We've been talking kind of about the gist of GIST. We've gotten to the genetic testing for GIST. Let's talk a little bit about the treatments and potential side effects. I'd like to start with Dr. D'Amato. Can you discuss and I know we've kind of briefly gone over it throughout, but a little bit more deeper dive. Can you discuss some of the current standards of care that are used to treat GIST and how well these therapies work?

Gina D'Amato: Again, first, whenever someone's diagnosed, we try to figure out is it curable or treatable? Curable means there's something that we can give you that could eliminate the cancer and never come back. Treatable means that we can treat it, keep it under control, and have you live with the cancer in your body. We may or may not be able to see it and that would be treatable. The first thing is we have to determine if that's possible. If it's in one location and it can be removed, then it's curable and the cure would be surgery. Now, the surgery should be done by a specialized surgeon that has expertise in sarcoma or GIST and has to be removed all in one piece and has to have normal tissue surrounding it. We call it negative margins because we have to assume there's probably some microscopic cells that can grow back if we don't get it all in one piece. Sometimes the tumors are too big or in locations that that's not possible at the time of diagnosis. If that's the case, then we can give treatment early on to try to shrink the tumor and remove it. That's where we would test the tumor for the molecular testing and see if it's the standard or the most common mutation. Exon11, we would start with standard imatinib, also called Gleevec. Every drug has several names to keep me in business, to confuse you, keep me in business, and stop treating yourself on the internet even though we love the internet because it's helping people and we're on the internet right now. That's my bad joke every once in a while. My poor patients and coworkers have to hear it all the time. [00:27:00] Gleevec or imatinib is the standard for if we're trying to shrink the tumor to remove it. Then we would treat for about six to nine months, get it the small size and then remove it or if it was just removed, we would look under the microscope and we would look at certain characteristics of the tumor to figure out what are the chances it's going to spread. If it's at high risk of spreading based on the size of the tumor, the location where the tumor started, and how many cells growing under the microscope called mitotic index, then we can decide, do we need to give you additional treatment to try to prevent it from spreading? The one additional treatment that we have available is imatinib. Average is about three years that we would place someone on imatinib to try to prevent it from spreading. Now, sometimes patients are at very high risk. Their risk is so high that we tell them no, you're not stopping at three. You're just going to take it indefinitely. Now, that's if it's curable. If it's not curable, meaning that it's spread to other locations, we have very good treatments to get it under control because you can live with cancer in your body as long as it doesn't affect the function of your major organ. You need your major organs to live, heart, lungs, liver, kidney brain. We need the brain. If we can keep the cancer, prevent it from taking up too much space in those organs, the organs can work, and we also have to protect your organs from treatment. If it spread, the first treatment that we usually use again, based on the gene mutation status would be imatinib. Unless they had that D842V, then it would be avapritinib, a brand-new drug. That would be the first and we would get scans every few months and see how it's working. Then if it's working well and the tumors are shrinking, sometimes we would remove those. If there's not that many, we remove those and then put back on Gleevec. If not, then we just keep you on that. Then at some point maybe never like Marina, it will grow, but about 10% to 20% of patients, it doesn't become resistant and just stay on the treatment. Now, other times you develop some resistance, and then that's when we would want to get either a biopsy or a liquid biopsy to see did it build up some sort of resistant mutations? If not or if the standard is, then we would go with second-line therapy. Second-line therapy is sunitinib or Sutent. That drug can work quite well for some time and then if that one doesn't work, then we have a third-line treatment called [00:30:00] regorafenib or Stivarga, and then the fourth-line treatment ripretinib or Qinlock. All of those can work quite well. Even Qinlock, if it stops working, we can even go to twice a day Qinlock. That's the standard, but again, we want to be checking for different mutations. If it has one of those other rarer type mutations like SDH deficient or NF1, we would do different treatments for that and likely we would try clinical trial from the get-go. Now, any time along those paths, if there's a clinical trial that's available with new drugs that we think may be better, we always offer the patient a clinical trial because we're always trying to get some improvement, but if there's not a clinical trial available, then that would be kind of the standard approach.

Ryan McDonald: Obviously, there's plenty of treatment options out there, all different types, but as with many things, there's always that chance of side effects. Sandra, can you kind of walk us through a little bit of some of the more common side effects patients may experience as a result of their treatment and how those are best managed?

Sandra Brockert: Imatinib or Gleevec, it's always the gold standard. That's always in our algorithm, number 1 so I'll start with that one. Common side effects on the imatinib are fluid retention. Many peoples get the swelling around their eyes, or they can get some swelling at their ankles, their lower extremities. The worrisome area to get fluid retention would be say around the heart or that, which is much rarer. But these are other reasons why it's good to go to a specialist that's used to giving these medications and used to managing the side effects and monitoring them. I'll kind of talk about side effects and give a little blurb about managing them quickly. For example, for the fluid retention, if it's not too bad, we can just recommend decreasing salt in the diet. If it gets a little more like the swelling in the legs, et cetera, we can give a diuretic to help pull off some of that fluid. Those are some things. A lot of people on Gleevec get these weird kind of muscle cramps that can happen at any time in their extremities or hands or that. All I can say for that is we monitor electrolytes, maybe taking some extra calcium or magnesium supplements. Point nine is electronic [00:33:00] water, staying well hydrated with your electrolyte balance. Any of these drugs can cause a little nausea and vomiting, maybe. With the Gleevec, in particular, people do better if they take it after a meal and with a big glass of water. Then sometimes the gas or diarrhea so it's OK to take some antacids and if you're having diarrhea, it's OK to take Imodium or if it's severe, even a prescription drug called Lomotil can help and watching your diet. Skin rashes can happen. Frequently, I talk to patients about even their skin feels a little more dry or itchy, so we talk about using creams and skin lotions, an antihistamine or an allergy drug such as Zotac sometimes be helpful. Then we bring patients in and check their blood counts because sometimes these drugs can affect the white blood cell count or even the red blood cell count so we want to make sure that you're not getting what we call neutropenia where you can be a little immunosuppressed or a little anemic. There's very rare, but it is a potential to affect the heart. We always do a physical exam and listen to your heart. You have to tell your healthcare provider if you're having these symptoms too. I wish I could call people routinely and just check in and say, how are you doing but in these days, we just don't have the luxury to do that, so we really count on you calling us or sending us a message to say I feel a little shorter of breath or I'm having more swelling in my legs. Don't just ignore these symptoms. It's better to call and tell us and we may have a simple fix for it. We may say it's nothing or we may say, oh, we need to get an echocardiogram, or we need to come in and check your blood pressure. That's another thing we got to watch on these medications, and we don't even want to start some of these medications if your blood pressure isn't already being well controlled. We may ask you to buy a blood pressure machine to have at home so that you can monitor it. Definitely tell your doctor if you're having any symptoms. Briefly, I would go through the other drugs too. The Sutent. These drugs can also cause fatigue, but I would say I see more fatigue with Sutent, nausea, vomiting, the blood counts, dropping, diarrhea, even thyroid issues. Sometimes we have to check your thyroid levels and make sure that you're not hypothyroid. [00:36:00] The really hard side effect for the drugs like Sutent and the regorafenib, the Stivirga are what we call hand-foot. It can be really painful blisters and palaces on the hands and the feet. We recommend starting with a urea-based lotion on the hands and feet before you even start these drugs just to kind of help prevent it. What we recommend is called Udderly Smooth. It has a cow on it, and it has like a 20% urea, but you may need to use these lotions on your hands and your feet and at night, maybe put it on your feet and put some socks on your feet. Again, watch the blood pressure with the sunitinib. The other thing, these drugs can also cause potential problems with wound healing so if you need a surgical operation or that, we may ask you to hold some of these drugs before and after some surgical procedures if you have an elective procedure scheduled. Then talking about the third line, the Stivirga or regorafenib, mainly I see with that drug, blood pressure, increase in the hand foot, diarrhea. Then the fourth line, the ripretinib or the Qinlock is actually tolerated pretty well. It doesn't have so much of the hand foot or GI, but it can cause hair loss. That's a hard thing to have as well. I frequently recommend people to see a dermatologist also when they're on these medications because sometimes we can get secondary skin lesions or a squamous cell or something like that, another kind of skin cancer. It's nice to have routine visits with a dermatologist, kind of do a head-to-toe check and make sure you don't have any abnormal moles or skin lesions. Again, the avapritinib that was mentioned, kind of a unique side effect to that drug is memory loss. There can be some cognitive function loss. I think the takeaway with any of these medications is to make sure that you follow up with your healthcare provider when you get started on them, make sure you call them if you have any side effects so they can help you manage them, come in routinely for blood work. They'll check for any drug-drug interactions to make sure everything you're taking is OK. I think that's about it. Thank you.

Ryan McDonald: No worries. Now, Marina, I saw you kind of smirk or smile at [00:39:00] one of the side effects that Sandra mentioned. Do you mind kind of talking a little bit about your experience?

Marina Symcox: Sure. Best thing for me for side effect for muscle cramps is to supplement with magnesium, potassium, and calcium. I use all three and yes, I have anema and swelling, but when I take diuretics on Gleevec, it just makes the muscle cramping unbearable despite the mineral supplements, so I have just opted for the swelling as the better of the choices. One thing that I mention a lot on patient forms when people just start is that at least with Gleevec, the side effects tend to diminish over the long haul. I've been on this drug for 22 years now and it's just gradually gotten a little easier and a little easier except for the muscle cramps. There is that. The other thing sometimes comes up, people will ask is this caused by my TKI. It's something that maybe is a little unusual, not in the standard shortlist. I tell people, I go to Google and get the prescribing information PDF that's there, and it will have the list of side effects that came out of the trial. At least it will help people see, yes, it's there. No, it's not. That's sometimes very useful on that. I will say that early on, I did have a lot of side effects and I've noticed some people do and some people don't, but just stay with it, your body adjusts. Now I have no experience with Sutent and the next line of drugs so I can't say about those.

Ryan McDonald: No worries. As we've talked about treatment, we've talked about genetic testing side effects and kind of the gist of GIST. We're kind of nearing the end so if you still have any questions that you'd like our panelists to take a stab at, please submit them in the Q&A box. We'll talk briefly about updates and changes in the space. If we can kind of get through that pretty quickly, that would help us catch up a little bit. Marina, what advice would you offer patients who are newly diagnosed?

Marina Symcox: Well, when someone comes onto our patient forum and they seem a little nervous, one of the first things I say is that GIST has become in more recent years, one of the more treatable, solid tumors. Keep that perspective. Then I'll give them my story because I have had metastatic disease for 25 years. I have never had a clear CAT scan and I'm doing OK. It is because of these new drugs. I do think it's helpful and the doctor [00:42:00] can speak to that about patients knowing where to find clinical trials online, and also maybe knowing when the major medical meetings are. I will tell you, I use Google News when I know when they are. At that time, there'll be press releases and I'll go into Google News and put in gastrointestinal stromal tumor. That's where I can find the latest news about new drugs coming out of the medical meetings.

Ryan McDonald: Dr. D'Amato, there's different things kind of in the cancer space and one of them is when the NCCN updates various guidelines for treatment. Can you talk a little bit briefly about what this means and what the guidelines have shown over time for patients currently with GIST?

Gina D'Amato: The NCCN guidelines are created from the experts in the field. Those guidelines are important for us to get treatments reimbursed and to help other doctors try to figure out how to treat. Over the past several years, what's been added to the guidelines, of course, are the new treatments that we discussed that are FDA approved. Also in the guidelines, I only mentioned five drugs that are FDA approved, but we have another handful of treatments that aren't FDA approved, but still can be effective in GIST. Those are other TKIs which are tyrosine kinase inhibitors which are basically medicines that stop that signal from being turned on so that the cancer cell doesn't get the signal from being turned on. Added to the guidelines where before if we were to switch a treatment, we'd have the patient off treatment for a long time then, oh, OK, this one's not working. Stop your medicine. Then you wait for the new medicine to come in couple of weeks off. Well, we know now that we don't want those patients to be off for too long. We want them to be on one. Another treatment is better than no treatment. Also added to the NCCN guidelines are mutation testing before you start a treatment and every time you want to switch. They have added that. They've added certain guidelines about giving imatinib beforehand if we can't remove it all or just leaving it in. Those have all been added to the guidelines along with the new treatments.

Ryan McDonald: Thank you. Sandra, I'm going to ask you the next question, but essentially actually I think it works because some questions have been coming in from the audience of this so let's pivot to kind of [00:45:00] our Q&A session and reminder if you have any questions and you were a little shy to, to submit them, send them in now. We have about 15 more minutes to go so we're going to try and get to as many as possible. Sandra, some of the audience are asking about kind of various immunotherapy clinical trials. I think this is a good opportunity to kind of briefly talk about some of the new developments on the horizon for patients.

Sandra Brackert: We had an immunotherapy trial at UCLA. The two arms was nivolumab versus nivolumab plus ipilimumab. The thing about immunotherapy trials is it's a different way of treating the GIST outside of that tyrosine kinase inhibitor like Dr. D'Amato was just saying that we want to turn off that signal. If you've gone through all of the TKIs and you've developed these resistant mutations, it's reasonable to look outside of the box. We've looked at immunotherapy and we did get some results of stable disease. We did get one patient that did have a complete response, but it doesn't work in everybody. Immunotherapy has been approved for several different kinds of cancers. It's not quite there yet. We had a smaller size study. It has to be looked at in larger groups. I think another reason why it's so important to do these mutation testing’s is we're trying to figure out why does it work in some people and maybe not so much in others. We do see that there's a PDGFRA D824V that those tumors may be more sensitive to a checkpoint inhibitor so that would be something maybe to use in that category. I'll just throw out another phase trial that's now in a phase 3 is more for an Exon17 mutation. It's the PLX9486 which is a combination drug. Their trial is combining the Sutent or sunitinib with this drug, bezuclastinib and seeing if that combination is more effective. They are seeing with the DNA [00:48:00] testing that the Exon17 mutation may be more responsive to this type of drug. It's just really kind of still figuring out things, I guess. I don't know.

Ryan McDonald: No worries. A couple of questions coming in as well and talking about treatment. I think it's an interesting topic because when people hear surgery, they're always a little concerned. It's daunting. I'm going to have to go under the knife. Dr. D'Amato, some people are wondering, is surgery always the best option or can you kind of do a watch-and-wait approach if your therapeutic is keeping your disease at bay?

Gina D'Amato: As we talked about, we have to figure out can we cure you? Can we eliminate the cancer totally from your body? Or is it OK to just not be cured, but keep the cancer under control and have you lived with it? Sometimes if the tumor is in a bad location and it would involve say removing the entire stomach or too much involved in the small intestines and it would be a huge operation, and the tumor is responding well to treatment and you're tolerating the treatment, it's OK to leave the tumor in. That's why it's very important to have all those discussions with your GIST expert and the surgeon, and really way the pros and cons. I've had several patients, mostly older patients, and the tumors were small. They were tolerating the treatment well, and they didn't want to go through a big surgery, and they did just fine doing that. There's many options and that's why really having a good relationship with your GIST expert is important.

Ryan McDonald: Also, there's quite a bit of questions coming in about clinical trials and participating and getting involved. Now, Marina, can you kind of talk a little bit about your experience with clinical trials and on the flip side of things, how GSI provides information about clinical trials?

Marina Symcox: Well, patient groups are like a grapevine, basically. You can go to and see the listing of trials, but if you're doing it from the outside, it's a little daunting because if you don't have a short list of the centers that you think are probably leading the field, and you can learn those in patient groups, and also patients can share their experiences like, hey, this is not working for me, or it has worked like that. For my case, I got in the first Gleevec trial that started in the summer of 2000. It's been going for 22 years and it really [00:51:00] did come from a patient group for lio mio sarcoma actually. A few people had joined the trial, and then everybody else who had a GI tumor that we didn't yet know was GIST, just glommed onto this trial. It filled up lightning fast. I didn't know actually what a trial was when I started, but now I know there's different phases of trials, phase 1, phase 2, phase 3. They have different goals. I think perhaps Dr. D'Amato can speak to that about the types of trials and what patients should expect from each phase of trial. I have witnessed placebo-controlled trials that caused anxiety, but I was in a phase 2 trial, which I think is kind of a sweet spot of a trial because it's disease-focused, they know the dose, and it doesn't have a control arm.

Ryan McDonald: Dr. D'Amato, do you want to take a stab at that in terms of the differences briefly and also too, kind of if you can address it too, some people are asking, well, what if my specialist doesn't recommend or offer a trial, what do I do?

Gina D'Amato: I think that it's important that, as I said, clinical trials can be very beneficial, but it's not for everybody in their phase and their stage of what their cancer is and where they are in their treatments. We always want to offer clinical trial if we think that it would be better than what we could normally have. Depends on what kind of mutations they have, what treatments they've been on, how their current treatments are working, whether we would recommend a clinical trial. I would say if you're on a current treatment and it's working, obviously we don't want you on a clinical trial, but at any phase where say it's not working and we need to switch treatment and the doctor says, listen, the current treatment isn't working, we need to switch treatment, then that's when you would say, OK, are there any clinical trials that I could qualify for that's better than what you're recommending? Then the patient and the doctor can go together on and they could see, OK, well, you've had this treatment, you have this treatment, let's see what's available. Then they can get a sense of, oh, no, I don't know about that trial. I think that may not be – I think I like the standard treatment better, or that trial you may have to travel too far for that trial or something that may not be feasible for you, or that doctor may not have the trial, but you're willing to travel. Some of the trials they do pay for travel. There's different phases of clinical trials. There's phase 1 [00:54:00] where you start out with a brand-new drug or a new combination. That seems scary because, oh, well, it's brand new, but doesn't always have to be a brand-new drug. Sometimes they're just combining the two treatments. They know one and they want to make sure it's safe and so you do get an opportunity to try something new. Then we have the phase 2 where everyone gets the same drug, everyone gets the same dose, and we try to figure out how effective it is. Then phase 3 is where they're trying to compare it with the standard therapy. We have, unfortunately, had several clinical trials with placebo. We didn't really like to do those placebo trials, the FDA mandated it, but I think now that we've had four placebo trials in GIST that I think that we can as researchers and patients, tell the FDA we are not doing any more of these placebo trials. Now, the recent phase 3s are not versus placebo, they're versus the standard. You really have a good chance, like, OK, well, I would normally get this anyways, like the one that we have with the Sutent, the sunitinib with the new drug, that combination, you either get the one or the two. If you weren't on the trial, you get the one. Again, it's important to realize where you are in your treatment, and then also the patient groups are great but if someone had a good response or if someone didn't have a good response, that doesn't mean you're going to have a bad response. You may have a good response or if someone had bad side effects, that doesn't necessarily mean you're going to have bad side effects because everyone's different and how we treat patients right now, the only way we know how it's going to work is if we try it on you and we see how you do.

Ryan McDonald: Now we're kind of nearing the end. Normally I'd like to kind of do a round-robin thing, which we'll get to in a second. I do think this question is very important to ask because we're in the business of educating our patients and really informing them about these topics. One question came in and I think it's really important because we're almost in the season of colds and flus and illnesses. Sandra, somebody asked my PCP always recommends things like the flu shot, shingles, pneumonia but I'm a little hesitant because I'm not sure how it'll affect my disease. Can you kind of provide a little insight on addressing that common concern?

Sandra Brackert: We highly recommend keeping on top of all of the vaccines and COVID vaccines and shingles vaccines [00:57:00] and everything because these drugs can affect the immune system slightly and make you a little more susceptible to the flu or that so definitely go for everything you would normally get, whether you're on the medication. Just keep up with all of your primary care needs for sure.

Ryan McDonald: Thank you. Well, I think we're going to kind of get ready to wrap things up so I'm going to go around to each one of you to kind of get your parting thoughts. Marina, I'll start with you. Anything you want to say before we sign off and mention about GSI?

Marina Symcox: Well, sure. We're on the internet. Our website is We also have a group forum on Facebook and there is a list serve too, where it's more of an email based, although I think people these days prefer Facebook because it's more amenable to your cell phone. I would like to also mention on the vaccines about the – I actually have a question. Is the shingles vaccine now recommended? Because early on we were being told not to get it. I ended up with shingles on my face and it went into my cornea, my eye, and I have to stay on antivirals forever, which is OK. It's managed but if it could have been avoided that would've been better.

Sandra Brackert: The Shingrex you can have that one now. I think so. Don't you think Dr. D'Amato, that it's OK?

Gina D'Amato: We recommend it for patients. I believe it's 60 or 65 and older, I think. I have to know this. I can't remember the age cutoff. We don't typically recommend it to our younger patients although 60 is pretty young still, anyways. We just recommend it for when your primary care would recommend it for you.

Ryan McDonald: Dr. D'Amato, any last parting thoughts?

Gina D'Amato: Well, first of all, I want to thank you so much for having this webinar and thank GSI. They've been so supportive and so helpful throughout all these years so really kudos to Marina and her group, really, really saved a lot of lives. Thank you for your good work. Second, I just want to give hope to all the GIST patients out there. When we go through the list of the treatments and then we talk about the side effects, it could be a little bit scary, but if you are going to your doctor regularly and you're talking to your doctor and you're discussing these, we can manage pretty much everything. Yes, you may have to be on one cancer drug and four medicines for side effects, but we can get [01:00:00] you and we can get you very good quality of life and we can get you to live as long as possible. There's hope out there and keep the hope alive.

Ryan McDonald: Sandra, close this out.

Sandra Brackert: That sounds right on. Thank you GSI. Thank you for doing these webinars. Thank you for inviting me. Thank you, Marina. I always tell people that you're the expert. We may be called an expert, but the person diagnosed with GIST on the medications, dealing with the side effects and their caregivers, it doesn't just affect the patient themselves. It's the whole family, their partners. You're the real experts and having these group discussions where you help each other and say, oh yeah, I have that, and this worked. I tried that, try this. I think it's more helpful than coming to see me. Don't forget to help your provider if you're having symptoms, anything that we can help with. I agree that we're always looking at new treatments down the line, combinations of treatments so there is quite a bit of hope. This is a fascinating diagnosis these days. It was when the first mutation-driven diagnosis and it's still leading the way. I just really enjoy being part of it so thank you for inviting me.

Ryan McDonald: Well, unfortunately, everyone, we are out of time, but if you'd like to watch this webinar again, it will be available on the Webinars-On-Demand page of within the coming days. I want to thank our panelists and the audience for attending and participating in today's event. I would also like to thank CURE and our partner GIST Support International for making today's educational webcast possible. Now, don't forget to check your email tomorrow for the survey to be entered in a chance to win a gift card. I want to thank you all for joining and we'll see you next time.

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