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

Darlene Dobkowski
Hello everyone, welcome today's live broadcasts of an Educated Patient Webinar: An Insightful Look at Advanced GIST and Available Treatment Options. I'm Darlene Dobkowski, associate editorial director for CURE. We are pleased to bring you this webcast presented by CURE and our partner, GIST Support International. We have 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 will be receiving a survey via email tomorrow. And as the thank you for watching the full webinar and completing the survey. You will be entered to win a Visa gift card. I am pleased to be joined today by panelist Dr. Mark Agulnik, City of Hope, Durate, California, Molly Finger, H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, and Marina Symcox, manager of the board of directors of GIST Support International or GSI. Now let's begin. Alright, so our first topic will be focused on the treatment for GIST and this question is directed for Dr. Agulnik. So before we dive into more specifics about treatment options, can you please provide a brief overview of the mechanisms of treatment for GIST Dr. Agulnik?

Dr. Mark Agulnik
Thank you so much. It's so great to be here today with my other colleagues on the on the Zoom. It's such an honor to be able to speak to patients from near and far. And to be able to write provide some information. So for those of us who treat cancer, we think of mechanisms very differently depending on the type of cancer that we treat. And so in the realm of sarcoma, we break things up into different compartments. And specifically, when we look at GIST we think that there are drivers that drive the GIST and it's important for us to understand this. And by drivers, specifically, what we're thinking about are mechanisms that are genetic mechanisms to the tumor, not necessarily genetic mechanisms to the body. And so it's not genes that are passed on from our families and our parents, but it is more specifically genes that are acquired in the tumor. And so it's very important for us when we send a specimen to pathology. If we send the specimen to pathology for the pathologist to be able to give us as much information as possible about the tumor, and specifically we're looking for what is driving the tumor. Most GIST patients will have a KIT mutation ... or they will have a mutation in PDGFR alpha, which is the platelet-derived growth factor receptor. And we know that we have several drugs that can target these pathways to enable appropriate treatment for our patients. We also look whether or not the patients that have other pathways that could be very important for us to understand in order to adequately treat the patients.

Darlene Dobkowski
Great answer Dr. Agulnik, so what are the four FDA-approved treatments for GIST?

Dr. Mark Agulnik
So currently, there are several FDA approved treatments for all patients with GIST so the majority of our GIST patients will first experience the use of imatinib, which is the first drug that is approved for most patients with GIST. At progression on imatinib, we have sunitinib, which is approved as a second-line agent. At progression on sunitinib, we have regorafenib which is approved as a third-line agent. And on progressing from regorafenib, we have pacritinib, which is an FDA-approved fourth-line agent. For a very rare subset of patients with a PDGFR Alpha exon 18 mutation or a mutation in D842V. These patients would have an FDA approved drug called avapritinib, which would be appropriate for them to use. And so as we look at the last several decades in the care of our patients with just we know that 20 years ago, we had one drug on the market 10 years ago, we potentially had three drugs on the market. And it's only been since about 2019 that we've now have five FDA-approved drugs for the treatment of our patients.

Darlene Dobkowski
So Molly, what type of benefits do these FDA-approved treatments provide patients with GIST?

Molly Finger
Thank you for the question. So in terms of treatment, when I think about treating GIST, I always think about the idea of wanting to provide some stability of disease for our patients. And that means that we want to both prevent progression of existing tumors, but also to minimize the risk for metastases, which are new sites of tumor that can develop elsewhere in the body. These drugs that we are now able to use, you know, provide an exceptional degree of disease management for these patients. And aside from that, of course, we're always thinking about quality of life. So I want my patients to live a life that is full of the things that bring them joy, and that are important to them. And so the idea here, again, is to help to minimize some of the symptoms that may be present as a result of their tumor. So those are typically our goals with treatment.

Darlene Dobkowski
So speaking of benefits, Marina, What have your experiences been with these treatments? And what have they provided you in terms of benefits?

Marina Symcox
Oh, gosh, provided in terms of benefits would be 22 extra years on my life. I was diagnosed with metastatic GIST three years before amatinib even became available. And so I went through the gamut of the treatments of that era, which didn't work very well. And I was actually in hospice, when the first imatinib trial came about in the summer of 2000. And I got into that trial. And I have actually still in trial today, I'm one of the small subset that has never developed resistance. Now, I haven't been on the second, third and fourth line drugs, so I don't have direct experience with them. But I did take great comfort that they are available now. In case there is resistance I have. I have several drugs to go through at this point. So I'm feeling very optimistic now after having once really gone to the brink with this disease. I've seen my children grow up.

Darlene Dobkowski
It's definitely important. Well, Dr. Agulnik, let's talk about the future. So what kind of emerging data are available that help prolong patients experience on these agents? So for example, studies showing the potential clinical benefit of dose escalation on pacritinib.

Dr. Mark Agulnik
Yeah, so first of all, just say, Marina, you bring me goosebumps, you're the reason we do everything we do, and to hear you talk and to hear you talk so eloquently about what the experience was like before and after really solidifies why we do the work we do. So thank you for sharing, I think everyone here will benefit and you give a lot of hope to people. So, back 20 years ago, when Marina would have been offered the first clinical trial, I think we didn't know very much about what we do. What we know is that Marina would have been offered a dose of imatinib that is going to be identical to every other patient on the trial. And we know that her weight and her height are going to be different than other people's weight and heights. But everybody gets dosed the same way. And so we know that everyone doesn't necessarily derive benefit from the same dose, and perhaps some need higher dosing. So over the years, we found that there are certain patients with an EXON9 mutation in just to potentially benefit from a higher dose of Imatinib and rather than use the dosing of 400 milligrams daily, they divided benefit from 800 milligrams daily. We know with respect to sunitinib that the FDA approved dosing is 50 milligrams for four weeks in a row in two weeks off, but I'm sure Molly could attest to most people can't tolerate that. And so we need to modify things to really make the patients from where they are. And every patient just doesn't tolerate the dosing just because the textbook or the study says they should get that dose. And so we often use two weeks on one week off for sunitinib we modify dosing to do daily dosing. Molly and I can both attest that Regorafenib at the FDA dose is not an appropriate dose for most of our patients. And that we she's nodding her head, we start quite low, potentially at 80 milligrams. We watch them very closely and we escalate but we're usually not going to get to the maximum tolerated dose. And I think what's very exciting now is what we see with repressed snap and the dosing that's recommended as 150 milligrams a day. And I think we've seen enough data now to suggest that if you progress on 150 milligrams a day of ripretinib, the appropriate next action is not to switch drugs, but it's to double the dose. And because it's a relatively easier drug to tolerate than sunitinib and regorafenib, and if it's less daunting for us as professionals to tell our patients to double the dose we never want to come across as flippant we want to come across as would we do this for ourselves. And so with regorafenib with sunitinib, it's hard to imagine some of those high doses with repressing it that becomes easier, which is wonderful for our patients. We know from avapritinib that the standard dosing is where we go but where we are today and where we'll be in five years is different. we circle back to Imatinib all the time and so we know that even if you progress, you potentially could derive benefit from it a decade later again. And so there is a lot of information out there with respect to dosing and that's that's really why you want to end up with an experienced specialist, because you want the expertise of someone who understands the nuances of dosing, and doesn't just necessarily use the package insert for recommendations.

Darlene Dobkowski
So you mentioned an interesting point, which kind of leads to my next question. You mentioned dosing. So why do some of these treatments start on a lower dose compared with others? Is there a method behind that?

Dr. Mark Agulnik
So why did we start on the lower dose and then escalate because truthfully, if we started on the full dose, the patient would never come back to see us it would just be unfair to them in most situations. And so we know that imatinib at 400 mg is well tolerated, we can manage the side effects that patients will see the periorbital edema, some of the skin toxicities, the labs to follow for blood counts for toxicity, very manageable. When you start to get to Sutent, and regorafenib, the dosing just isn't as tolerable. And the side effects with respect to the hand foot syndrome becomes very debilitating for patients. And so you want to dose at a lower dose to allow the patients to become adjusted to the medications, you are moving through medications that have different side effect profiles, and you want them to really be comfortable with it. I know that Molly's team, they see patients quite frequently potentially someone reaches out to them every week, we do the same thing. If you leave a patient three or four weeks without reaching out to them once you start them on specifically regorafenib, and potentially sunitinib, you're not going to succeed with them being able to maintain their doses. And so we, just like Molly's group, call them every week or we bring them into the clinic every week to really make sure that we're maximizing the care that we're providing. There's a lot of resources out there. There's a lot of good things with respect to proper foot care, proper foot attire, looking at the shoes, they're wearing to make sure that they have enough question, giving them the right creams for their hands and their feet, having a dermatologist involved early on, making sure that you have enough coverage of, of diarrhea, watching the labs very carefully. So there is a very strict nuance to this, and you want to set every patient up for success. And the only way to do that is to start low and then slowly escalate.

Darlene Dobkowski
So doctor, you do mention the side effects. So the patient does happen to experienced side effects, should they stop the treatment should use? Should they just be open with their team? How should they proceed with that.

Dr. Mark Agulnik
So definitely open with the team. So I think that the relationship that you have with your medical team is very important. And I think the last thing you ever want a patient to say is I didn't want to bother you. So I didn't let you know. So I say to everyone, it's not a bother, if you let us know early on, it certainly makes it easier for us to overcome some of the side effects. And so you don't want to keep pumping a drug into someone that it's it's causing unmanageable side effects when we talked about it before Molly nailed it when she talked about, we're trying to preserve quality of life, we're not trying to hurt people. And you look at Marina, I mean, you look robust, you look healthy, one probably doesn't know that you're on the treatment. And so that's the goal when we treat our patients is to really keep them where they are. We want them to continue to work, we want them to continue to have families to be functional and society to enjoy life. And so you want them to reach out to us early, it's much easier to control things before they get escalate poorly. You sort of think about the patient who gets chemotherapy, and that's for other diseases. But all of us treat patients with chemotherapy, and you certainly don't want someone calling you. After five days of vomiting from nausea. It's much easier after the first time they vomit. And so when these drugs the moment your hands start to feel a little tingly, we want to hear about it the moment you have two episodes of diarrhea, we want to hear about it. We want to be able to offset the side effects very quickly so they don't escalate.

Darlene Dobkowski
Now Marina, what type of side effects did you experience while undergoing treatment and will be easily managed by your care team?

Marina Symcox
Well, importantly, I find at least for imatinib, the side effects greatly diminished over time. So 22 years out on imatinib. Now, I do have a few side effects, but they're, they're minor. But when I started I did have severe side effects. I was in a very weakened state had been in hospice had been on traditional chemotherapy, and I was also in clinical trials. So I had a direct path to the clinical trial nurse and coordinator through email and also my local family doctor I live in a small town in the family doctors offices, six blocks from my house and he was very attentive. So some of my worst problems. He actually was the one that intervened for me and actually told the clinical trial team what I needed so don't overlook an accessible family doctor at times if you can't get through to your oncologist office, they can sometimes help too. But I would say side effects now I have very A few now I realize that the the pen inhibitors punch more side effects. But I think that compared to the alternative of the traditional cytotoxic drugs, these are a lot easier to deal with over the long term.

Darlene Dobkowski
And what type of advice would you give to patients who may be experiencing side effects while on their treatment?

Marina Symcox
Well, you do have to think about things incrementally and don't project too far into the future. If you look into into the distant future, "how can I keep going on this way," it can be daunting. I had a hospice nurse telling me before I met, and it was even available, and we had never heard of it. You know, you just have to live with blinders on at times. And so you know, when side effects are bad, just take it that day in don't even think about what you're going to be able to do the next day. And if you do it that way, then you only have to deal with the day in front of you. And then you just keep plodding along that way. And you'll look back and see you've actually covered a lot of time.

Darlene Dobkowski
Now, Molly, are there any other side effects that maybe patients will experience on treatment? And then also another question: Are there any certain dietary restrictions or even considerations that patients may have to consider while undergoing treatment?

Molly Finger
Or thank you for the question. I think there obviously are a number of side effects. If anyone has spent any amount of time looking at a drug insert, you can see that there are a number of things that have been reported during the course of a clinical study that are documented. As far as kind of what I would say, our most common side effects and how we educate our patients. We certainly talked about fatigue. And I will say to patients, most likely, everyone will have fatigue to some degree, the amount of fatigue, of course, is dependent upon the person, they are an individual. So as much experience as we have with these drugs, there are, of course, the individual factors and comorbidities and other medications that certainly can play into that. GI side effects like nausea. Sometimes, depending upon the drug, there can be, you know, diarrhea, and those types of things. And so we often try to provide patients with a measure of prophylactically treating, or at least having something on hand so that they're not surprised by that. And then I would say, as Dr. Golden had mentioned earlier, a lot of our patients will talk about muscle cramps, periorbital, edema, things like that. So we certainly have recommendations and guidance that we provide to patients patients during the course of it. So to just add on to what Dr. goldhamer said, usually what we will say in terms of how patients can be successful, and that is basically we want patients to over communicate. So as Dr. Agulnik spoke to earlier, patients will often say, "Well, I didn't want to be a bother." And by the time that patients kind of get in touch with us, and usually they'll wait until their next appointment, things have progressed rather quickly. So again, just that guidance of I will say to patients, if you're not feeling well at home, and your symptoms are your side effects are impacting your quality of life, then that was a reflection that I have not done my job. And so I want patients to know that I would much rather have the time the conversation with them to talk about side effects and how we can treat those, as opposed to patients kind of filling in the blanks or just having a miserable couple of days. Specifically, regarding the question about diet, this is a question we get very frequently in the world of oncology. And my approach may be different than Dr. Agulnik, so certainly would appreciate any feedback he might offer as well. But I typically say to patients that for me, the approach is, you know, everything in moderation. Again, my focus for my patients is wanting them to maintain a quality of life. And so I certainly wouldn't say you know, a big dessert or a heavy, you know, red meat dinner every day, I certainly want my patients to be able to celebrate, you know, big moments in life anniversaries, birthdays, and holidays. And so, I will just tell people, you know, obviously think about food as fuel. So make sure that you are eating small frequent meals throughout the day. And then you know, don't overthink the the food component of it. And again, as I've said before, everything in moderation is typically my approach.

Darlene Dobkowski
Dr. Agulnik, did you have anything to add about them?

Dr. Mark Agulnik
I agree. I agree. It's like we've worked together forever, Molly. I agree. 100%. I think the purpose of all of this is to live life. And when people ask me, Should I restrict x, y or z? Should I not drink alcohol? Should I not have sugar? I think the purpose of these treatments, I say to them, their disease was not meant as a punishment, so they don't have to punish themselves in the process. And so really, I do recommend that people live their lives. The one thing that we haven't talked upon is the toxicity to the wallet. And so I think that it would be unfair not to acknowledge that these costs of these drugs are very high. And I don't want patients to feel like they're isolated and alone. There are some great programs through the pharmaceutical industries in order to provide access to these drugs. to patients, and I think that patients shouldn't feel like they have no choice and they have to pay out of pocket these huge sums. I think it's very important for patients to work with social workers, to work with advocacy groups to work with the pharmaceutical companies in order to try to get some access to drugs, that allows it to be much more manageable, and so that they're not losing everything in the process of trying to win back their lives.

Darlene Dobkowski
Well said, this is mainly a question more directed towards Dr. Agulnik and Molly. How can patients weigh the quality of life and clinical benefit goals while on treatment? And when is the right time for patients to consider transitioning from one treatment to another? Especiall because earlier in the conversation, we did mention how there are all these lines of treatment?

Dr. Mark Agulnik
Correct? Is it OK, Molly, if I start?

Molly Finger
Absolutely, I was hoping you would say that. Okay, so I think

Dr. Mark Agulnik
Marina really summed it up for us, actually. So we could have started with her. So what she said is, the side effects today are not what they were when she first started. And I don't want to misquote you. But I think that's what you said. And so essentially patients and so had she said, I'm not going to accept whatever, whether it was periorbital edema, or diarrhea or skin changes, or fatigue, fatigue sometimes gets better after a few months. So I think what's important is to set expectations and put things into defined periods of time. And so if you think about what is acceptable to you, so if I said to you, you would have to put up with some fatigue for three months to get 20 years of life, most people would say that's acceptable. If I told you, you'd have to have 20 years of fatigue, where you're not leaving your house, most people would say that's unacceptable. And so I think you have to find that balance, and everyone's tipping point is going to be different. And so are you going to get a piano player to go on a high dose of Sutent, or Regorafenib, in the hands peeling and they can't use their feet for the pedals of the piano? No, that's not reasonable. And so then you sort of have to come up with a better solution for them and better drugs are you going to get people that are going to be so going to be able to get on some of these drugs, where they really won't have that fine use of their fingers? Probably not. For the most patients, though, you can alter dosing, you give a few breaks, if you go two weeks on one week off, it becomes more manageable and you lower dosing, you give them a little time to recover, you work very hard with your supportive care or palliative care, you work with your dermatologist. So I think it's really a balance, I certainly don't think you just have one side effect, and you throw it all out. I think you need patience, you need a few months to try to figure it out. And really accept that the benefits can ultimately outweigh the risks. But having said that, besides Marina, we're not taking these drugs. And we have to be cognizant of the fact that we're prescribing something that we ourselves do not take. And we actually don't know what it feels like to have those side effects. And so we just have to accept where people are. And if people can't do something, they can't do it. And it's not our job to make them feel bad about not being able to do something, it's our job to support the minute and find an alternative for them.

Darlene Dobkowski
And, Molly, did you want to add to that?

Molly Finger
Yeah, just a piece kind of adding on to what Dr. Agulnik said, again, is kind of my role is sometimes acknowledging the difficulties that patients are facing, so that they don't feel as though they're complaining or being ungrateful, right. Because sometimes we get in that mix, they're like, "Well, you know, I have another friend who has cancer, and they didn't have this opportunity or this much time." But I, you know, allow that space for patients to kind of grieve some of the things that they may have lost. And even if it's temporary, you know, as a result of their treatment, I think that's a certainly a thing that we can do. And then also giving patients some permission, right, as Dr. Agulnik, spoke to, sometimes I will say to my patients, "Hey, listen, if you have a big event coming up, and the medication that you're taking to treat your just causes significant fatigue, diarrhea, something like that, maybe we take a break for a couple of days, a couple of weeks, so that you can enjoy that event and not feel, you know, so, you know, significantly impacted by the side effects of your therapy." So again, it just comes back to the open lines of communication, making sure that patients are aware that, you know, certainly this is not a one size fits all. And sometimes we do have to make accommodations or adjustments to dosing and or dosing schedules. And again, it's just about having those conversations with patients and making sure that they're aware that that's, you know, something that we certainly are capable of working with.

Darlene Dobkowski
So while you did mention adjusting schedules, for example, if there's a big life event coming, what advice would you give patients to let them know that it will not, hopefully not have a great impact on their, on the control of their disease?

Molly Finger
And again, I'll let Dr. Agulnik kind of jump in certainly he has more experienced but in my experience with, you know, with GIST tumors is that, you know, the idea is that I want my patients to be on treatment more consistently than not, which means that if we have to pause for side effects, or it's toxicities, then we absolutely will. And if patients have something, you know that it's kind of coming up, and they're saying, you know, I want or need a break, either because of something mentally kind of working through some of the things happening in their life or with their disease, or because of, again, side effects or toxicities, and that's certainly something that we can do. So for me, as a clinician, it honestly is about, again, providing that open door and that space for patients to talk about not only the side effects that they have for their treatment, but kind of the impacts to their quality of life and things like that. So again, it's just about having open lines of communication. So again, encouraging patients that, again, your provider should be kind of a soft spot for you to land. And certainly, we want to give patients every opportunity to speak about the whole person self as far as their experience with their disease, because they are not just just they are not just cancer, they have families, they have jobs, they have lives. And so we have to incorporate that into each decision that we make regarding their care.

Darlene Dobkowski
Now speaking of an open line of communication, Marina, how did you discuss or communicate questions and concerns with your care team? And how did you discuss treatment and patient management goals with your team as well?

Marina Symcox
Oh, gosh, well, when I started, we were dealing with terminal disease and the short-term life expectancy. So I felt like my care team ... very candid ... I was on my learning curve. I didn't know the difference between a sarcoma, a carcinoma at that time. But because I was seeing them frequently, they were the ones guiding me to the next treatment, and telling me what to expect, and telling me you know, really about what to expect at the end of life. When imatinib came along in the trial, it was a very exciting time, and there was a lot of new science and a lot of bustle about it. And so self education was very helpful. And very, we were all very motivated to do that. So I feel I pretty informed now. And while I haven't had anything that really need it needs at the moment, at a candid conversation with my oncologist I do feel prepared, you know, it's helpful to learn the vocabulary and learn some of the key concepts that expedite your communications with your doctor. If you can do that, if not the patient, then a caregiver in the patient's orbit can be that person.

Darlene Dobkowski
That Marina, you did mention you informed yourself, you educated yourself, what type of sites or resources did you use to do that?

Marina Symcox
Well, in 1997, I was put on a cytotoxic drug and we went to the local medical university library and got papers on it, it started reading, I mean, it that's kind of how it started. But early on, my one of my family members found a sarcoma patient group on the line, and that group doesn't even exist anymore. But it was actually for leiomyosarcoma, because at the time just wasn't quite yet a separate disease entity. But those people pretty much taught me everything. In fact, some of the early trial doctors were on that website communicating with us. So I'd have to give a shout out to George Demetri he was on that website. And he's the first one then informed me that that I didn't have my own bias or comment I had GIST and it had a KIT driver. I mean, he told a whole group of just patients online that in 1998, so it was very exciting time, but you don't learn everything in a day, you, you just stay connected. And just keep reading, read what other patients say and forums, and you will gradually through immersion, figure out and learn the concepts. There other patient experiences. And now there's a lot of resources online. There's a lot of professional resources online that patients can access, and one would be the nccn.org, the National Comprehensive Cancer Network, they have treatment guidelines. And with a free registration you can get in there they have a PDF file to download other geared for doctors. And with a little bit of background information, you can indeed follow the ones for doctors and kind of learn the concepts.

Darlene Dobkowski
So I'm gonna kind of open this question up for everyone. Obviously, we know the importance of patient advocacy. But why is it also important for patients to advocate for themselves during treatment? I'm going to open the floor up to everyone so feel free.

Dr. Mark Agulnik
I think the medical field is a very difficult field to navigate. And I think as an individual patient, it's daunting. I think it's intimidating. I think it's hard to know who is an expert and who isn't. And I think that there's a lot of fear that if you quote unquote "interview" your physician or your nurse practitioner or your team, that you can be viewed as disrespectful or difficult. And that's not the situation, you need to approach it the way you approach any major decision you're going to make in your life. And so you're not going to buy the first house you look at, you're not going to you do inspections, I think there has to be some degree of advocacy for yourself to get a family member to come in and listen with you. During COVID, we saw the devastating effects and people coming all by themselves to all these doctor's appointments, and there was no one to guide them. And people were so isolated and family members are sitting at home or sometimes on a phone, it's not the same as in person, if you could do it in person, I think that you really need to make sure you this is a rare condition. So it's not like high blood pressure, diabetes. Some of the other conditions where the majority of Americans have a problem. It's not heartburn, it's things that really needs an expert team. And as Marina said, if you live in a remote area, or if you live in an area that doesn't have an expertise, you sort of get the person who's closest to you to become an expert with you. And you give rope them in, you give them the tools to be successful. You have the experts in the big senators who don't live near you, guide and help and George Demetria. As we mentioned him who really is the guru and has educated so many of us in this field. Really you use the resources where they are and you allow your physicians to reach out do one on ones and talk to other people. There's still a video now and telemedicine there's so much more access today than there was even five years ago. But I think that as a patient, you have to get the information and find a way to make sure that the person you're seeing is an expert, I think just international life raft. liferaft I know for a fact I think just international does as well. It will have a list of experts in your area. And you could put in your area, your zip code, what state you're in, or what city you're in and find if there's someone who's who self identifies as an expert. So it is it is an honor system where someone puts themselves in. But it is an honor system, someone who doesn't have an interest in just isn't going to do that.

Darlene Dobkowski
Marina, Molly, anything to add to that?

Marina Symcox
On the patient forums, sometimes our goal is to train someone to navigate Google on their own. For example, if someone says they live in a state that's not really known to have a major sarcomas center that they don't know to go to Google and type in their, their state's major medical university and sarcomas center. And you show them how to do that. And it's like, look, there's a list of oncologists. And someone here actually even has just in their credentials. So showing people how to navigate on their own is, is really valuable. And that's where patient forums are pretty good with that enabling people also add that, even now, 25 years into this my time in the clinic, I'm nervous, even though I know that the scan is OK. And there's really not a word, I'm nervous. And that's not actually when I'm at my best. So when you can self educate at home, through reputable websites or having other the patient grapevine kind of steer you, that's when you can actually do the bulk of your learning. So you're prepared? Do you don't have a lot of time in the clinic with with your medical team? It's you need to be prepared when you go in there.

Darlene Dobkowski
Molly, did you want to add anything?

Molly Finger
Sure. I think again, here's what I my years of pediatric experience kind of come in. And that is, you know, when I was in that environment and listening to the parents and believing when they would say that, you know, this is not normal for my child. And so, for me, as a clinician, it's about listening to what people are saying and taking it at face value and wanting and being able and willing to investigate further so that we can get answers. And so I always will tell patients that listen, you are precious, right? And if you would do this for one of your family members, then I need for you to know that you know, you're worth it as well. And just again, the reminder that you know, even though we can think about things, you know, from the standpoint of this is typically how they work or this is what we do. Again, every person comes to the clinic with their own set of comorbidities, other medications that certainly can make, you know, this venture a little bit more interesting. And so, you know, again, just reminding patients that we are a resource as much as they need for us to be offering you know, patients to see another sarcoma specialist if they have, for whatever reason, maybe lost some trust to faith or just need someone else to say what we're doing does make sense. And then also, you know, for us, it's about, you know, providing that avenue for patients that maybe don't have direct access to a sarcoma specialist or a sarcoma program. And kind of, you know, again, kind of strengthening those relationships with community oncologists so that patients don't feel like they're giving up anything. Because we oftentimes will say, Hey, we've communicated or we've worked with the physician that you're seeing before, and certainly any questions that kind of come up along the way, but again, it's just reminding patients that they are worth it. And, you know, certainly providing again, those avenues for them to express any concerns or worries that they may have.

Darlene Dobkowski
Now, moving on, Marina, how did you stay motivated throughout treatment? And what advice would you give patients in that department?

Marina Symcox
Well, when I was diagnosed, 25 years ago, I had small children. So the motivation was to live long enough so that my youngest child could actually have some memory of me, she was two years old at the time. But that was my initial motivation. But once imatinib came along, and it's frankly, been a fairly easy, easy time of it, once I got through the first year, the first year was hard. So staying motivated, now it's not too difficult. My GIST was not a theoretical risk on my life, it actually was a real risk that took me to the brink. So there's nothing like having your back against the wall to stay motivated on the treatments. Now, if you're in adjuvant therapy, you're you're just as more of a theoretical risk. And for that reason, you need to have personal discipline and perhaps in the aspect of your life, find things that motivate you to do something that's difficult, whether it's relationships with other people, a hobby, a goal of being around to see something important happen in the future, like that. Spiritualism, hobbies, whatever, it's going to depend on the individual. But for me, it really was my children. And they really weren't even that old when I got to imatinib. But imatinib has not actually been very challenging for me to stay the course, to be honest, it's been a good match for my tumors and done pretty well on it.

Darlene Dobkowski
So Molly, what are some of the best practices for patients to stay motivated at such a difficult time in their journey?

Molly Finger
I think that Marina had kind of alluded to this or spoken to this earlier. But it's this idea of finding, you know, yourself in the presence. If we get too fixated on, you know, these milestones that sometimes don't necessarily happen, you know, in the right time, at least for us, that can be very difficult. And for me, also, it's kind of, you know, asking patients to think about what are their goals, like having a goal every single day that may be small, and maybe having a bigger goal and working towards that. So I think like anything that can, you know, somewhat seem overwhelming or daunting in the beginning, you have to kind of break it down into the parts and pieces and kind of attack the things that you can and focus on the things that you quote, unquote, can control, and then kind of go from there. So it is a day to day having a goal. And like I said, for me, as a clinician, it's opening up the space for both good days and bad days, right. That's the reality of what all of us live, but certainly is true for our patients that are dealing and being treated for just so that's my advice.

Darlene Dobkowski
Dr. Agulnik, obviously, not all treatments are the same. And experiences may vary from patient to patient. So based on that, what advice would you give to patients?

Dr. Mark Agulnik
So I think you have to walk into a treatment with the assumption that treatment is going to work. I think that if you walk in a defeated, you end up defeated, and I don't think every personality is able to do that. But to the best of your ability, I think you have to believe that what you're going to do is going to have an impact on your life. And I think that you have to think that it's gonna have a positive impact. If a patient says to me, which is not uncommon, you start to go for side effects. And the moment you start with the first one, they say, I'm gonna get that and then you do the second, they say I'm gonna get that too. And then you give the third and they tell you, you're gonna get that I could guarantee them, they're going to get them all. And it's not a switch, you can't turn your personality diff to make it different. But I will say you have to walk in with the belief that this is going to be beneficial that you have the power that you have the strength to get through some of the side effects that you have the support system. And then if you don't have a built in support system around you, you use the advocacy groups, and you use your physician team and you use your nurses and your nurse practitioners, advanced practice providers to help you. But I really think that when you walk in, you have to walk in with the trust that the team has your best interest at heart. You have to believe that the team is talking about you in a positive light when you're not in the room, and that everyone is wishing you do well. You want your team to have those butterflies every time they see that there's a scan coming up because they want to open the scan and see that the scan is good. You want your team to be rooting for you. And so it's really creating this long-term relationship. If you're able to have this disease for 20 plus years, you probably are going to see different physicians over time. But if you start at the same time at the same age with your first physician, you may have a 20-year relationship longer than some marriages. And so I think you really, you really, you really want your you really want to develop that relationship where everyone's on your side, and you need to approach it, I think as positively as possible. That's not to say you can't go home and cry. That's not to say you can't punch a wall. That's not to say that you can't have a bad day, bad week, bad year. But in the grand scheme of things, hopefully many more of the days are positive than negative. And hopefully you don't feel like you're in a situation where it's not worth it.

Darlene Dobkowski
Alright, so now I think we're going to open up to questions. And I'm going to start off with because I noticed when Dr. Agulnik mentioned, you may have numerous doctors I saw Marina shaking her head. So Marina, do you mind talking about your experience with working with different doctors and how did you maintain your poise?

Marina Symcox
I actually don't know how many oncologists had most of them were racked up before year 2000 though. But I actually had didn't I had didn't have a bad doctor along the way, just circumstances led me to another one. Since imatinib, I have been a patient I initially started the trial at OHSU. Now I'm a patient at Dana-Farber. So those are long-term relationships. Before I was sent to MD Anderson, I had actually been to UCLA and another place and I remember in California, so there were quite a few doctors along the way. The constant was my family doctor who actually felt the mass in 1997. It was like, oh, no, he was the constant throughout the day, he would come to my house, he guided me into hospice, he actually lied about my condition, so I could get a chance to be seen in Oregon for the trial, and then I kind of squeaked into the trial. So you I've kind of lost track of where I was going with. Refocus me a little bit.

Darlene Dobkowski
Sure. How did you feel, you know, even though your relationship with the doctors didn't really end on a bad note, it was just circumstantial. How did you how did your confidence in your care team continue despite different?

Marina Symcox
Well, I, I was sent to major sarcoma centers from the get go, because at that time, there were no treatment. And my local oncologist was always the backup person that who implemented with a sarcoma center recommended. So I have always had that dynamic. And then with self education along the way, I would learn independently information and then when I would hear them say it to me, it's like, yeah, that's what I had read. So there wasn't any guesswork on my part, you know, what are they saying to me? I actually had learned it independently from from them.

Darlene Dobkowski
Alright, so I'm going to open up the Q&A to everyone that's here. One of them for the audience is can you discuss the different stages of just and how do you define advanced?

Dr. Mark Agulnik
I'm not the biggest fan of staging of GIST, I just don't think it relates as it relates to other diseases. I think what is more important is, is it surgically resectable? Yes or no? Do you need adjuvant therapy? Yes or no? And then do you have advanced disease or metastatic disease, and that's how I compartmentalize it, I really put it into a few little buckets. And for me, that's the easiest way because the buckets help dictate the care we give. And I think if we start to assign labels to people as you're a one, or you're a two or three, or you're a four, I'm not even sure what a three or four is, I know it very well in other sarcomas. And just I just don't think it's something we traditionally use. And so I would focus a little more on the extent of disease, the organs that are involved, and what the current status of the diseases is.

Darlene Dobkowski
Molly, did you want to add anything to that?

Molly Finger
No, I think it's perfect. And that's actually why I got a little nervous when he jumped off for a second because I was like, in my kind of experience. We don't really talk to me since about staging, per se with with regards to just and so I'm glad to see that. We're not alone in that. So thank you Dr. Agulnik.

Darlene Dobkowski
All right, so speaking of surgery, Dr. Agulnik and Molly, if you want to chime in as well, where does surgery fit in as an option in current treatment guidelines?

Dr. Mark Agulnik
Surgery is a huge benefit for patients. It's not a benefit for every patient, but it has to be viewed and it has to be on the table. When I meet with people, people for the first time when I tried to make sure they are aware of, we could put everything out there, it's like a buffet, you don't need to take everything at the first go around, you have an opportunity to go back and take different things. And so we certainly want to look at the role of liver-directed therapy, we want to look at the role of surgery, there is a role for radiation, not for every patient, but for some patients. There's a role for CyberKnife, there's a role for drug therapy. And so we have it all on the table. So I think for patients with surgically resectable disease of don't have metastatic disease, that's a given surgery is the answer. For patients who have metastatic disease, if, let's say you have five areas, four of them are very well controlled, one of them is acting differently. The one who is acting differently probably has a different signature, like a genetic signature. And that's a good one to go after surgically. And so you will do surgery, if you feel like you're losing control of one or two things. As the disease progresses, you often want to sometimes do surgery in order to get better control again, but you then stay on the drugs. And so I think if you lose sight of the fact that there is an armamentarium of different opportunities and different people that need to be brought in, then you really lose sight on how do you get someone from today to 20 years from now.

Darlene Dobkowski
Anything else on that topic? Before you move on to the next question?

Marina Symcox
I actually have a question about surgery to remove large primary tumors when metastatic disease is present. When I was diagnosed, surgery was the only option. So I had a very large tumor removed, despite metastatic disease. And I see patients comment now that their primary tumors are not being removed, because the disease is already metastatic, I as a patient kind of would want it out anyway, what's the general recommendation on that?

Dr. Mark Agulnik
I usually use an analogy of a boat with holes. And what I say to someone is I get it as a patient, it makes sense. But I sometimes think if you have eight holes in a boat, if we fix one, it doesn't really achieve what we're trying to achieve. And my worry always is when someone goes for surgical resection. So if you had your surgery, and the anticipation is to get on drug therapy shortly after, if you have a complication or a side effect, you can't go on drug therapy. And so the surgery may actually ultimately hurt your chances at getting control over your disease. And that's the last thing we want for people, imatinib is relatively easy to use peri-operatively. And after surgery, some of the other drugs have washed out periods because of wound healing issues. And so we need to be very aware that it's the surgery is all for the majority of patients, it's it's easy, quote unquote, easy. But if you're the patient who ends up with a wound complication, the wound isn't healing, you're not getting onto your other drugs. And so while you've spent all that time fixing one hole, the other seven holes are growing a little bit worse. So I don't traditionally send people for surgery, if they have widely metastatic disease, because I want to try to get control of everything before I take them.

Molly Finger
Just to add to that, I will say that kind of the approach that I say to patients is you know, as Dr. Agulnik that kind of spoke to earlier the metaphor he used about, you know, being a buffet, I will often say to patients, it's not a question of can we because the answer to that question is always yes. Could I or can we consider radiation surgery, liver-directed therapies, cryoablation, through whatever it is? The answer is yes. The better question that I want patients to think about and one that we will spend the time talking about is the should we part right? And so that's kind of, you know, to what Dr. Agulnik had spoken to, which is, we could do it, but ultimately, what is the benefit versus the risk going to be for the patient? And those are the things that we take very seriously. So while we can acknowledge and recognize that patients want to get rid of this alien that is in their body, right, sometimes it's not the right time, or it's not the right choice. And, you know, those are guided discussions that we have, and ultimately, you know, some patients may choose to proceed with surgery despite our recommendations. And that is, you know, an individual choice. But again, the the thought behind it is always about the ship part for us rather than the can we because that's an easier question to answer.

Dr. Mark Agulnik
I find that there are two baskets that patients often really hold on to, that us as treating providers don't necessarily hold on to. One of them is they need to have surgery. And so that's the point that we were just discussing. The other area that patients often really hold on to is that they want their tumors to shrink. And when we talk about stabilize or control it, and we know that patients don't do better now necessarily if the tumors shrink, they need to just stop growing is where they have to be. But patients really hold on to that. So there are some things that inherently as human beings, we attribute value to, that maybe is not medical, but it still has value. And so the surgery thing is something people put a lot of value on, even though we don't see the value of it often. And it's the same with they need something to shrink to feel that something's happening. Whereas we see scans that are completely stable, and we're ecstatic. And then you see like the air sucked out of the room, because it doesn't translate when a patient gets disappointed. And so there are some barriers that it's our responsibility to help people overcome.

Darlene Dobkowski
So another question we got from the audience is, is there any point in time in remission, that you could go off meds or reduce steps?

Dr. Mark Agulnik
So the short answer is probably not. So I don't really see this as a disease of remission so much, I see remission more in my leukemia, lymphoma colleagues, patients. For our just patients, I see it as do we have control. And maybe that would equate as remission, I don't see it very often that we're able to eradicate all phases of disease, with the use of these drugs. And because we can eradicate all sites of disease, they usually have something that we could follow. So for the average patient, if there's something to follow, I would leave them on these medications and not, not not try to sequence them off of it is the long answer. Short answer was no.

Darlene Dobkowski
So with that sequences to take to is can you skip one of those and go to the next one? Or does it have to follow that exact sequence? Like, do you have to go on imatinib to sunitinib and then follow that line? Or can you skip around?

Dr. Mark Agulnik
So I think, I think if the insurance companies were savvy, they would make you go in the order that is FDA approved. And I don't think there's wrong of doing that. As a practicing physician, and if it was my body, I think there are some situations where I would want to skip around. Those are those are what are the nuances. And that's why sometimes it's worthwhile to get into a lark, long car ride or an aeroplane if you could afford it, and go see an expert because they'll bring the expertise. And so there are some situations where I will skip around for certain exon mutations, where I think that some of the other drugs have a better opportunity. I'll make some adjustments based on patient's circumstances and situations. Certainly dosing, I'll modify based on age and what people's needs are. So I do move around. And so the four don't always go in the order. It's unlikely that I move out of Imatinib, its first line, I'll say, but I don't always use the next three in the sequence. But I think that if we think that 50-plus percent of patients are treated by medical oncologist that are not just specialist, I think that it's important to stay in the sequence because the sequence is what's been found to be most beneficial for patients based on the studies we have. And if I was an insurance company, I would probably try to enforce that sequence.

Darlene Dobkowski
So a couple more questions before we finish up. One of them: obviously, Marina mentioned that she was in a clinical trial. So what is the best way for patients to kind of find those clinical trials and participate in them, and stay up to date?

Dr. Mark Agulnik
Yeah, so from my standpoint, I recommend that people look at clinicaltrials.gov. And then you navigate it either in a very helicopter view of the world, and you just put in just, and then you'll get 132 options, and you have to figure out how to narrow it. And on this side of the screen, there's an area that says actively recruiting and so that's a great one to tick off, because you don't really need to know what is what's closed five years ago. And so if you press that you probably go from a few 100 down to maybe 52. If you're living in the middle of the country, doesn't matter what's happening in Seoul, South Korea, probably not. And so then you quickly can move it to what's in the United States. And then you could easily filter it down to what is within 50 miles of your home. And then you sort of look at that. And if you go 50 miles from your home, and you put just and you put actively recruiting, you probably will end up with four. And so it really will narrow it down quite nicely for you. And then if you if you open each one and you scroll down at the bottom, there'll be a contact number or an email. There's not a week that goes by if not every two days that doesn't go by that I don't receive an email from someone asking about a clinical trial that I have ongoing. There's usually email addresses phone numbers, I'd be hard pressed to find a group anywhere in this country that's not going to answer an email from a patient that's requesting access to a clinical trial. And if someone's emailing me from Miami, I'll tell them to go see John Trent or Gina tomato with some of the valley made from elsewhere in the country. I'll divert them to where to go because we all know each other so there are so few sarcoma specialists in the country that we could help the patients divert to where they need to be. And so clinical trials.gov is a great place life raft on their website has access also to clinical trials. But I think clinicaltrials.gov probably is the most comprehensive.

Darlene Dobkowski
Marina, did you have anything to add about how you found the clinical trial that you participated in?

Marina Symcox
It was actually through the patient forum. My husband was, he was actually the university professor, and he was home for the summer. And he started reading the email flow, it was a listserv at the time, and a few patients started discussing this trial, and people were actually benefiting and you know, I was in hospice, I was upstairs in bed, he actually made all the arrangements and at that time to just cancers were not even tested for kit expressions. So he had to arrange to get three oral tumor blocks tested for KIT was positive for KIT. And then he did all the arrangements to get me into to be seen at one of the trial sites. That's how it happened. Patient forums are really an excellent place to pick up on the grapevine of what's possible. People will discuss how they're doing or mentioned, the trials, or if someone like me will send a link to clinicaltrials.gov saying, look, it's during the trial sites for the drug we're discussing. So I think that's a good thing to know. And then also, eventually, you want to know what has happened in these trials. Sometimes in clinicaltrials.gov, they will have a tab say that you can click on about results. And you can read that. But the best way to find out the exciting news is to follow Google News and type in just gastrointestinal stromal tumor in June because that's when the the major ASCO meeting happens. And when we get releases about trial information, so use Google News, not not straight up Google but the News tab, and just type in gastrointestinal stromal tumor, and there will be press releases about the latest trial findings that have been published.

Dr. Mark Agulnik
The other can also give a shout out for sorry, is every cancer center has a health care librarian. And so if you are not savvy, you can't do it yourself. If there's a language barrier, which a lot of patients have a language barrier, the librarians will be able to pull the information, do all the searching on clinical trials.gov for you. And so they're a great resource for patients. And so with patients that aren't able to do that themselves, this is where they should go.

Darlene Dobkowski
Now, speaking of resources, is there any? What's the importance of finding a just treating specialists? And how do we find them? Some? Some of you did mention Google, but are there any other ways to find those specialists?

Dr. Mark Agulnik
I think Marina had clarified so I think that you would look at so I think you could majority of just specialists will be sarcoma specialist, I think there are a few. If there was not a sarcoma specialist at a designated cancer center, then I think usually the team that treats stomach cancer, colon cancer, rectal cancer would be the group that would take the just patients. And so I think if you look for in local cancer center, you type it in, and some of the advocacy groups to find it, you could go with Marina mentioned NCCN guidelines. So the NCCN guidelines has were listed as authors. And so you could use that list. We're not trying to do the witness protection program. We're out there, and we're trying to help people. And so I think that through any of these resources, but usually, if you live within 50 miles of a university, type up the university Google sarcoma specialist and see what you find.

Marina Symcox
Another thing I can add as you could was the nccn.org offers is a great way to do it, but also go look at a phase three trial. That's a large phase 3 trial but have a list of the trial centers. And you can assume that those trial sites have a just or sarcoma specialists. That's another way to do it. For some of these trials will have a lot of sites.

Darlene Dobkowski
Well, unfortunately, we are out of time. If you'd like to watch this webinar. Again, it will be available on the Webinars on demand page of cure today.com 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 Chair and our partner just support international for making today's educational webcast possible. Don't forget to check your email tomorrow for the survey to be entered to win a gift card. Thank you all for joining. We'll see you next time.