Chemotherapy vs. Immunotherapy Webinar Recording - Apr. 2024

Alright, everyone. Let's go ahead and get started. Good evening, and welcome to tonight's webinar about treating mesothelioma with chemotherapy versus immunotherapy. My name is Sean Marchese. I'm an oncology writer and registered nurse at the mesothelioma center. I've been a panelist on our previous information sessions, and tonight, I'll be your moderator. Before we start the presentation this evening, I wanna get started with a few guidelines and tips for tonight's session. Tonight's event is going to be jam packed with information about mesothelioma treatment, but cancer treatment is not one size fits all, which is why nothing you hear tonight should be taken as medical advice. A treatment plan needs to be customized for a patient's unique situation based on their medical history, current health, stage, cell type, and more. That's why you should always consult with your doctor before making any changes. While our presenter has years of experience working with patients, we are not your doctor. In fact, we're not a treatment facility. We're an advocacy organization. If you're looking for additional information about mesothelioma treatment after tonight's event, we encourage you to consult with a mesothelioma specialist. You may have noticed that your mic is muted. It will remain muted for the remainder of the event, including the q and a session. We do want you to ask questions though. Feel free to submit them at any time through the chat box. You can do that by clicking the chat icon at the bottom of your screen, typing in your question, and clicking enter on your keyboard or screen if you're on a tablet or phone. Don't worry. Any messages or questions you send are private, so only the panelists will see them. When it gets to the q and a part, I won't say who submitted each question. We will try to answer every question after the presentation, and we'll also send you a recording of the presentation in a few days, so don't feel like you need to write everything down. Now I'm excited to introduce our speaker, doctor Jay Marie Suga. Doctor Suga is an oncologist at Kaiser Permanente Vallejo Medical Center in California. She specializes in helping develop the latest cancer treatments, including those for mesothelioma and lung cancer. She also serves as medical director for Kaiser's clinical trials program and as chair of the Kaiser Permanente National Lung Cancer Program. She is not affiliated with asbestos dot com. Thank you so much for being here, doctor Seguin. I'm sorry. I think you're on mute, doctor Suga. Thank you. Thank you for having me. I'm very excited to be here and being able to talk to you all. Okay. Thank you so much. Well, with that, I'm gonna hand over the mic and the presentation over to doctor Souguette to get started. Alright. Well, thank you. So, so, you know, I'm really excited to just be talking to you just in in general terms about, what kind of treatment we often think about for mesothelioma. I will not be going into surgery just to, be, very clear upfront. We will really be talking about drugs, you know, med medications that we use to treat mesothelioma. So I plan to just go over, given kind of the topic, just the general, classes of drugs that we use for mesothelioma. The first main, drug, that we'll talk about is chemotherapy, and I've listed a few of the chemotherapy drugs I'd like to go over. I'll also just briefly touch on something called vascular drugs, which, can be used as an adjuvant to the chemotherapy, so something that we sometimes will add on to chemotherapy. And then we'll also talk about the immunotherapy space. After that, we'll also kinda go into some of the future directions of where mesothelioma might be going in terms of treatments. Can you go to the next slide, please? So first, I just wanna say in general what chemotherapy is versus, we'll talk more about what immunotherapy is, a little bit later. But chemotherapy are basically drugs that are developed to really combat fast growing cells. So, you know, fast cells in your body typically, can include the the cancer cells typically are much faster growing than your normal cells, so that's why they affect your, cancer cells more than they will affect, normal cells. So the one thing about chemotherapy is it's not necessarily specifically tailored to, say, mesothelioma cells, but they're tailored to any rapidly growing cells. And so because of that, and the chemotherapy has been developed, you know, to combat various different ways to target fast growing cells. You know, it is is more of a general platform to use for treatment for cancer in general. So that's where we've started with chemotherapy. I wanna just go over kind of the main classes of drugs that have been proven to work really well in mesothelioma. So the first class of drugs that I'll just speak upon is called the platinum drugs. So the two most common that are used for mesothelioma is something called cisplatin or carboplatin. So, again, this is not specific to mesothelioma. It's active in a lot of different cancers. Actually, cisplatin is one of the drugs that, are, have been used for decades for different types of cancers. In general, there's been more trials, clinical trials for mesothelioma that have utilized cisplatin versus carboplatin. However, we do have some good data that carboplatin is a very good substitute as, in general, it works almost as well as Cisplatin and has generally a lot fewer side effects than Cisplatin. So oftentimes we will substitute carboplatin, for cisplatin because of that, effects. So the main side effects for all the platinum drugs, generally speaking, happen to be nausea, vomiting, also what's called neuropathy, numbness and tingling of the hands and feet, lower blood counts, like becoming anemic or low platelets, that can slightly increase one's risk for bleeding, or the immune system, the white blood cells, can be lowered as well. Again, the immune system can be affected, so that's why you can be at higher risk for infection. It can also affect, the kidneys. And the other thing, because of the neuropathy, it can also affect the nerves in the ears and cause either ringing of the ears called tinnitus or hearing loss. Next slide. So the other medication that is, considered extremely active in mesothelioma in terms of chemotherapy is, something called Pemetrexed or, the brand name is Olinta. So this is FDA approved for mesothelioma, and it's it's considered an antifolate, type of drug. It's active not only in mesothelioma. It's used extensively in lung cancers as well, adenocarcinoma specifically. And what's been shown is the combination of a platinum drug plus this pimitrexed works extremely well in mesothelioma. If you look at some of the trials, like, there's a trial that looked at just using cisplatin or using the combination of cisplatin and pemetrexed, it increased the, the ability that the drugs would, affect the cancer and shrink the cancer, significantly. Forty one percent chance of the drug responding versus seventeen percent for just using cisplatin alone. So we often will combine a platinum plus the pimitrexed as our ideal, choice, for treatment. It also showed that, it took longer before the cancer started to grow again by using the combination of the two and also increased, survival rates. So I think that the the ideal situation is to get both a platinum drug plus this pimitrexed. Some of the main side effects to pimitrexed is that, I would say one, two, and three is fatigue. Fatigue is probably the most common thing we see with pimitrexed. And, actually, we actually use, some vitamin supplements, vitamin b twelve and folate to try to combat that fatigue, you know, effects that Pemetrexed has. Swelling, swelling of the legs can happen, rash, lower blood counts, again, affecting the immune system can occur, and also affecting the kidneys as well. So I will say that the platinum drugs and the pimitrexed are our most active chemotherapy drugs, and often, again, they are put together in combination as first treatments, or first or second treatments for mesothelioma. Now I'm just gonna go into a couple of other chemotherapy drugs that could be utilized, after, you know, we try the platinum or we try pemetrexed, the first drug that I'm gonna talk about, there, is a chemotherapy called gemcitabine or sometimes known as GemXR. So it can be active by, by itself. It could also be combined with the platinum as well, like cisplatin or carboplatin. And we again, this it generally is thought to be a little bit less active than the, Pemetrexed or Olympta and and platinum combination. So it often be reserved for after, you know, we've utilized those drugs first. So perhaps in the second or third line setting. The main side effects for gemcitabine tend to be very similar again to the other chemotherapy drugs. So nausea, low blood counts, affecting the immune system, potentially affecting the nerves, although it's usually less so than the the platinum type of drugs. And it can also affect the liver, and we monitor that very closely on treatment. And potentially, it could have some pain at the injection site. I do not wanna mention that all of these chemotherapy drugs that I am going over are administered through the I the intravenously through the IV. And then finally, the the other drug that I just wanted to mention, that can sometimes be used in mesothelioma is vineralbene, also sometimes known as navalbene. So again, it's similar to the gemcitabine or gemzar where it's best used probably by itself, but it could be combined with other treatments like the platinums. It has been shown to be effective in improving, symptoms, you know, if symptoms is a major issue, and and increasing the response rates as well. But, again, utilize probably after you've used the combination of aplatin plus pemetrexed. Again, a similar type of side effects, you know, their their, nausea, you know, got GI type of side effects, tend to be a little bit more prominent. Lower blood counts. It can affect the nerves again as well in the liver and pain at the injection site. So as you can see, a lot of the chemotherapy drugs have very overlapping symptoms or side effects that we, manage, with these treatments. So, the next class of drugs that I just wanna go over very briefly is called, anti angiogenesis drugs, and I will specifically talk about a medication called bevacizumab or Avastin. So what is angiogenesis? So angiogenesis is the process of formation and maintenance of new blood vessels. Genesis meaning new and angio, you know, meaning the vessels. So it's, you know, important for all, you know, living tissue to have blood vessels, you know, and oftentimes will need to, provide new blood vessel growth to heal from wounds or surgery. And so it's something that is, utilized by the body to make new blood vessels. So important for tissue viability and growth, wound healing. But cancer can also utilize this mechanism as well to actually spread and grow. So there's something called VEGF, vascular endothelial growth factor that that's a signal that is provided by the cancer cells, right, and other, you know, normal cells as well. But the cancer cells can can send out this signal that then there are receptors on, any a cell that can actually, start this process of forming new blood vessels. So the receptors will be activated, because of the VEGF signaling that is, sent out, and then, and then the the they will be able to form new blood vessels. Now so these drugs like bevacizumab, is potentially to block these new receptors to help decrease the spread of cancer and, formation of the new blood vessels. So one thing that has been shown, in the lab is that mesothelial cell mesothelioma cells have very high levels of these VEGF receptors, meaning that it's a very important part of how they grow and spread. Go to the next slide. So that's, the basis of this drug called bevacizumab or Avastin. It's an antiangiogenesis drug. So one of the things is that it doesn't work by itself. It has to be combined with chemotherapy. And generally speaking, with the chemotherapy combination I just went over, which is the platinum plus the pimitrexed, It doesn't really work by itself, so it's kind of an add on to chemotherapy. Number one, to enhance the effect of the chemotherapy and, again, hopefully, to work on the blood vessel growth. Now, bevacizumab does slightly increase, side effects of general chemotherapy as well. So something to keep in mind and something to weigh in the decision of whether to add bevacizumab. There is also some unique side effects to bevacizumab or Avastid that, oncologists usually generally have to weigh whether or not it's worth these, side effects potentially, for a particular patient. So there are some patients that maybe oncologists would think maybe bevacizumab is not worth the risk of that. So the patients that are not necessarily great candidates for receiving this drug are patients that might have high blood pressure or potentially, a history of heart disease. Also, this particular medication can increase the risk of blood clot. So if if someone has a blood clot history or is at high risk for blood clots, it might not be a good drug for them. It also can sometimes affect the kidneys. So if your kidneys are the kidneys are initially impaired, then it may not be a good drug for that particular patient. Also, because it does impair wound healing, If there's any thought that there's going to be any surgeries, then it's not something that you'd wanna start. And then, it also can increase the risk for bleeding as well. So anyone who is at high risk for bleeding, or have, say, low platelets that also can increase one's risk for bleeding may not be a good candidate for this particular drug. So what is the evidence for bevacizumab? So there is a large study called the MAPS study. So the MAPS study actually looked at adding bevacizumab to the combination of a platinum plus, which is cisplatin and pemetrexed. And what they were able to show was in this very large study, they added about three months additional, time for survival. So that equates to about a decreased death rate about twenty four percent over the study period. So based off of this one study, some, oncologists may consider adding bevacizumab to that platinum combination with pemetrexed. So now that I've gone over the chemotherapy portion of, of the treatment for mesothelioma, Let's talk about immunotherapy, which is, you know, kind of a brand new segment of drugs that we are now able to utilize, you know, for mesothelioma patients. So, can we go back to that slide just for a second? So one of the things is that there are actually several there are two drugs, two, classes of drugs that we kinda think about when we're targeting the immune system. So one class of drug is called anti PD one or anti PDL one. So and then the other is, one that's called anti CTLA four. So what I wanted to just, convey is that they target the immune system in different ways. One the first, set of drugs that, I'll talk about really is looking at seeing if we can allow the immune system to actually see the cancer cells as being foreign. So one of the things that cancer cells do is that it has the ability to cloak itself and and really kind of evade the immune system. And there's the signal that they put on this the surface of the cell called PD l l one that is able to do that. And the immune cells really, see that, and they they they can't really, identify it as being foreign. And, you know, cancer cells are tricky in that way because, you know, cancer cells are actually evolving from from our own normal cells. And so oftentimes, it is very difficult for the immune system to be able to identify cancer cells as being foreign and use mechanisms that they would normally use, to, like, destroy, you know, invaders, like infections and things like that. So so what it's trying to do, these these immune cell, immunotherapy drugs is trying to, help the immune system to recognize it as being foreign. Now the other class of drugs that I will go into called anti CTLA four actually works in a different way where it's actually basically revving up the immune system itself, to actually go, be activated. So it's one of those things where we're taking pressure off of, the gas that you know, we're actually putting pressure on the gas pedal to get it to be activated to go out and find those, invading cancer cells. So let's go into it a little more in detail. So I'm gonna just focus on the bolded ones. So the p d one, p d l one inhibitor drugs that are most commonly used. One is called nivolumab or Opdivo, and the other one is called pembrolizumab or Keytruda. The other, drug CTLA four inhibitor drugs I'm gonna focus on is called ipilimumab or Yervoy. So let's go into that. So nivolumab, again, is one of those drugs that is really trying to help the immune system find cancer cells as being forward. Now it had been studied, by itself in mesothelioma and shown to be effective. But now we have evidence of a, even better response with combining it with that other class of drugs called ipilimumab. It can be given at any time on the patient's treatment journey either at the very beginning, before getting anything else for any drugs for mesothelioma or can be given later as well. The FDA has approved this particular medication for a lot of different indications, and we use it quite regularly, in a lot of different cancer cells. But, of course, mesothelioma is the one that we're focusing on and ipilimumab, and ipilimumab, has been shown to be even more effective, especially, together versus just by itself. So we we wanna sometimes think about using both of the drugs at the same time. So the FDA in October of twenty twenty, identified that combination as a good treatment option for first line treatment for mesothelioma patients who have not received surgery based off of a very large study called CheckMate seven four three. So I wanna go into details about that particular study. So CheckMate seven four three was a very large phase three study. It's over six hundred patients, which is a really big, number of patients for mesothelioma, which is a relatively very rare cancer. And so the promise of this, trial is, they wanted to, enroll patients who'd never received any treatment and didn't undergo surgery, to either the combination of the, immunotherapy drugs that we talked about, nivolumab and ipilimumab or Opdivo and Yervoy versus the chemotherapy combination, cisplatin and pemex pemetrexone. So they enrolled a bunch of patients, and what they were able to show was survival did, was improved in the immunotherapy group over chemotherapy. They were able to show a twenty six percent decrease in risk of death, during the study period for the immunotherapy group. So eighteen months versus fourteen months overall survival rates on average. So based off that, the FDA did approve the combination the immunotherapy combination as we mentioned. So, just to note that, actually, the immunotherapy combination group had more side effects, five serious side effects, five percent versus two percent in the chemotherapy group. So when you analyzed the CheckMate seven four three data a little bit further, we actually find found something that was very, very significant and that it really depended on what type of mesothelioma, the patients had, how well they did. So if you group the patients that had epithelioid type of mesothelioma, survival rates, were relatively similar. It was maybe slightly better for the immunotherapy group, but it was relatively comparable between chemotherapy versus immunotherapy. However, what we saw a very big difference in was those patients that had biphasic or sarcomatoid tumors where there was a significant difference between the two groups, where the immunotherapy group did much better. So, survival rates for that those particular patients were over double, those that got just chemotherapy alone. So, clearly, a lot of the overall results of CheckMate seven four three were driven by the fact that the biphasic and sarcomatoid patients did a lot better with immunotherapy. So I think based off of CheckMate seven four three, I think, you know, the use of immunotherapy either in first line, or second line can be really considered, and I think that's something, that, all oncologists will need to think about. So I'm just gonna briefly talk about pembrolizumab because pembrolizumab is similar to nivolumab, and it is FDA approved, as, a treatment option, for pleural mesothelioma. It it has been approved for second line treatment as of June of twenty twenty based off some data that, that is doing that. One of the things I wanna just mention though is if somebody received nivolumab or nivolumab and ipilimumab, it is unlikely that they would respond to the also getting pembrolizumab, and so it's not, something that I personally would recommend. But the mechanism is relatively similar. One of the things that has been noted is that, some of the the patients that have what's called high tumor mutation burden, which means there's a lot of mutations in the cancer cells. And those that received previous treatments and don't have other alternative treatments, other treatments, and they didn't receive immunotherapy before, I think pembrolizumab is a good option. So I mentioned that actually side effects some serious side effects could actually be a little bit more with immunotherapy. So let's talk a little bit about the main side effects of immunotherapy. So the one thing that I always stress to patients is that it can cause inflammation of any part of your body. So, anything that ends with an it is in a medical term is, you know, is basically, inflammation. So, like, you know, if it's affecting the colon, it's called colitis. If it's affecting the liver, it's called hepatitis. If it's affecting the thyroid, it's thyroiditis. So there's a lot of different types of potential, side effects that immunotherapy can cause. Now in general, immunotherapy, is relatively, you know, has some side effects. But, usually, severe side effects is pretty small in general. The common organs that are affected, I would say, most commonly is the thyroid, so low thyroid levels causing fatigue. And oftentimes, you will have to give thyroid replacement, drugs, you know, to combat that. If it, you know, again, if it affects the colon or the intestines, it can cause diarrhea. It can affect the blood making cells. It can affect the liver. It can affect the skin, the nerves, the muscles, the joints. So it can cause a lot of inflammation in various different places. But, again, you know, some of the other organs affected that are less common, but we sometimes do see and can be sometimes fair, is in other hormone producing organs such as pituitary or adrenal, sometimes can affect the heart, called myocarditis, the lungs, again, pneumonitis, or the kidneys. So, you know, in general, I don't think that the severe side effects is, common. One of the things is that, it's very, very important to monitor side effects, and communication is the key here. We always need to do blood tests prior to each treatment, and that's true for chemotherapy or for immunotherapy, but it's just something in general that we really need to do. And to also communicate with your clinic, clinical team and the or the physician. The So one of the things that's unique about immunotherapy versus chemotherapy is the the timing of when these, side effects occur. So for chemotherapy, the side effects are pretty much, in a it starts, most commonly right after you get the treatments, and then it takes a couple of weeks, perhaps, you know, depending on which treatment you're getting, and then you can start to feel better. So you feel bad at the very beginning, you know, a couple for the first week or so, And then you start to feel a little bit better from the side effects as as you get farther along. But that you you then go in for your next, you know, treatment. So it's kind of this, wave effect where you start to feel bad, and then you start to feel better, and then you're going back in for treatment, and you feel bad again. For, chemotherapy, the one unique thing about immunotherapy side effects is that it could happen at any time. It could happen after your first dose. It could happen after your thirty fifth dose. So, you know, it's not predictable in terms of when some side effects can happen. So, again, communication is key. If you're able to tell your your clinical team that something is going on, if you're not feeling well, it's good to really just make sure they are aware so that they can look and see whether or not it could be related to these medications. So some of the steps that an oncologist, could take, you know, if you do have side effects from these treatments is number one, often will be to stop the drug itself. Give some time off the drugs, see if, the side effects get better. Depending on the severity, sometimes it would be important to start, what's called steroids. So steroids, can actually counteract the fact of immunotherapy because it actually suppresses the immune system. And so it kinda calms the immune system down because oftentimes, what's what's happening is that your immune system is revved up, from these drugs that it starts to attack, your own body. It was similar to kind of autoimmune diseases often. But, But often, you have to start at a very, very high dose of steroids and really be on steroids for many weeks and have to have a very slow taper off. And steroids has its own set of side effects, of course, that can include kind of jitteriness or insomnia. It can affect the muscles and the bone strength. It can cause weight gain, for a lot of people. So just something to be aware of. But it there is a way to kinda stop, you know, the side effects of immunotherapy. So there are also some other treatments that could be recommended depending on which organ is affected and or the severity of the side effects. So something that, we will custom as well. So now I'm just gonna go into, some promising treatments to keep an eye on. There are many different, potential trials that are going on, for a lot of different, cancers, including mesothelioma. So I just wanted to mention that there are some potential, new options in the horizon. So this is kind of a a schema of, of some of the the ways that, that researchers are trying to, target the mesothelioma. There is a particular protein that's called mesothelin on the mesothelial, that mesothelioma cells that, has been shown to be a way that, we can develop custom drugs to try to target that, and be able to target the mesothelioma cells specifically. So I think those are potentially pretty exciting. There are again, there are immunotherapy drugs. There's beyond the ones that I discussed, there's definitely a whole host of other immunotherapy type of drugs that are being looked at in terms of a potential benefit. And we're actually gonna talk a little bit about the one on the lower right called vaccines so that there is actually a potentially new vaccine that might be really exciting and and potentially available in the near future. So what I see as kind of the next, wave of, information that's coming out from mesothelioma, There are some ongoing very large clinical trials looking at combining both chemotherapy and immunotherapy together as a first treatment option. Remember, we talked about chemotherapy versus immunotherapy, but what if we are able to combine them? It's something that we often will use in lung cancer treatment as well. So so it's something that, us lung cancer docs are pretty familiar with doing, combining both chemo and immunotherapy. And so there's a couple of large studies that we're waiting the results of something called beat meso. Dream three r is another one that, has not yet been reported out. So we're looking into that combination of chemo plus immunotherapy. We didn't talk about surgery, of course, but, again, surgery in some, patients might be a consideration for mesothelioma. And, you know, we're thinking about whether or not to use immunotherapy just prior to surgery and whether that will be helpful in those situations. I'm just gonna skip over to to a couple other things. So you probably have heard about tumor treating fields using electrical fields. There is a protect a treatment option that has been FDA approved, which is a device, you know, called Optune. And so that's something that, that some patients would potentially, be recommended. And then there's, finally, we're gonna talk more specifically about, UV one vaccine. So let's go into that. So this is something that is, brand new, and I think we're still getting more information about UV one cancer vaccine. So I think vaccine is something especially kind of in this day and age. You know, cancer vaccines have been looked at for for many years. I think now that the technology is evolving, I think there's been more excitement, potential excitement for cancer vaccines. So this one might be one to look out for. So in just a couple months ago, February twenty twenty four, the FDA fast tracked, this UV one cancer vaccine, for pleural mesothelioma that are not eligible for surgery. So it's, it's actually a treatment, a therapeutic vaccine. It's not for prevention. And it's based off of a study called the NIPU study that just was, reported out, last fall. And what that study showed was that, they looked at patients, about a hundred and eighteen patients, I think, were on that trial, and they looked at looking at the immunotherapy combination of nivolumab plus ipilimumab and whether to add eight injections you you know, what's been reported out is that that the survival appears to be potentially something, intriguing and potentially something that could be useful for patients. So median survival was fifteen point four months for those that received the vaccine plus the immunotherapy drugs versus eleven point one months if they just received the immunotherapy alone. And so what's thought is this this potential cancer vaccine is gonna enhance the immunotherapy of immune effects of, of the immunotherapy drugs. What was kind of a little bit disappointing was that, the what called, aggression free survival was, not, super exciting, meaning, like, we're not sure. It only lasted about four point two months in the UV one versus two point nine months in the non u v one. So, technically, you know, their primary endpoint, which is basically what is what the first question that they're studying, was looking at, progression free survival, and that that was not met. So that was considered negative. But because the survival rates, did favor the combination, the FDA, was interested enough to kind of fast track it and probably get more information about whether or not this could be a useful thing in the future. So it's not available yet, just to say that, but it is something that the FDA has kind of granted as a potential, interesting, new treatment option. So we'll we'll be looking out for, more information in the near future. So in conclusion, I think cancer treatments, especially for mesothelioma, are are evolving, and there's some exciting things in the in the horizon. So I I think that that's one thing about, being an oncologist is that things change all the time. And so I think it's really, really great to see advances like this. Mesothelioma is a rare cancer, so I think one of the main things that, you know, I think that, is important to be, sure of is that you see somebody that, regards themselves as a mesothelioma specialist so that you could potentially hear about and know about the latest, greatest treatments that are potentially available. So that with that, I'm gonna conclude my presentation. That was wonderful. Thank you so much, doctor Suo Suo for another amazing presentation. So it's now time for the q and a portion of our webinar. We've already received quite a few questions, and there are more coming in. So if you have a question, just remember that you can click on the chat icon, type in your question, and click enter on your keyboard. And remember, only the panelists will see those messages. Before officially transitioning to the q and a portion of the night, I do want to remind everyone that nothing said on the webinar is medical advice, and you should always talk to your doctor before making any changes lifestyle or treatment related. I can't stress this enough. I see we still have more questions piling up, so I will keep us moving along with our first question of the night. Okay. Doctor Sudha, this person has said that their partner has epithelioid peritoneal mesothelioma. But because he carries the BRCA gene, his medical and surgical oncologists have recommended a a specialized chemotherapy regimen rather than immunotherapy. Are you familiar with why this could be? So, so that's a great question. Number one, just to state, you know, and I know I I think I saw a couple of questions that specifically pertain to peritoneal mesothelioma. You know, I think that, that a lot of the treatments that we use for pleural mesothelioma, do get translated, you know, to peritoneal mesothelioma. Although I think there's even less, you know, studies that are potentially generated just because of the rarity of that disease as well. And so, you know, I think that's one thing to just kinda keep in mind that maybe some of the comments that I've made on pleural mesothelia may not necessarily be the ones, the most appropriate for peritoneal mesothelioma. But to say that yeah. So with BRCA mutation, they're recommending, chemotherapy, versus immunotherapy. So I think that that's very intriguing, and I think this, what called BRCA, mutation is actually something that sometimes can be very sensitive to certain types of chemotherapy drugs. Like, actually, the platinum drugs are considered to be, you know, there's been a heightened sensitivity to the the effects of platinum drugs. So, it's very possible, you know, that the, treating team was thinking that using a platinum drug might be beneficial in a patient that has no BRCA mutation versus the versus immunotherapy. There are other, drugs that are potentially in other cancers, not mesothelioma, that has been that BRCA, potentially can treatments, have been developed. So it's also possible that they're recommending, you know, some of those treatments that, have been used in other cancers and seeing whether or not they'd be useful and beneficial for mesothelioma BRCA patients. Great. Thank you so much for that answer. This next person says that they were diagnosed with mesothelioma epithelioid mesothelioma last year. They completed five and a half rounds of chemotherapy, on carboplatin and pemetrexed, but had to stop due to a reaction. What are the typical next steps for people who get reactions to, chemotherapy like that? Great question. So, you know, oftentimes, there can be reactions that happen after being exposed to chemotherapy drug, especially the platinum drugs. We we do see that sometimes in the clinic where, you know, after you know, certain amount of exposures, they actually people do get a reaction. And depending on the severity of the reaction, sometimes, the chemotherapy drug, would be either stopped, you know, and not recommended to continue. Or sometimes there's something called desensitization, which is where they would kind of try very, very small amounts of chemotherapy, you know, to see whether or not the reaction would recur and give also other medic supporting medications to try to, calm the reaction down. So depending on kind of the situation, sometimes that could be utilized. But I would also say this, you know, I think, five to, you know, usually, the chemotherapy combination is given for about four to six rounds or cycles. And so if, the patient already had five cycles, that may be enough treatment, you know, to give a break. Oftentimes, people need breaks right after getting that many rounds of treatment. And so often, just kind of observing, you know, after getting that combination, for a little while and rescanning after several months to see, you know, if the cancer is, you know, stable. Is it still shrinking, or is it growing? I think a lot of times that's the approach that's taken after about, you know, four to six rounds of chemotherapy. Great. Thank you. So for this next question, this person says that, they were diagnosed, with epithelial mesothelioma and were, were treated with immunotherapy. But they're planning on waiting a month or two to start treatment, after their diagnosis, because they're planning to check some things off their list, they say. But they're in stage three a according to their PET scan. So in your opinion, doctor Suga, how, is it okay for someone to delay the start of their treatment, based on the stage or or the type of mesothelium that they have if they're planning to start immunotherapy if they have some other things they wanna do first. You know, I mean, I think, again, it does depend a little bit on the situation and and, understanding, a particular patient's disease course, you know, because sometimes, you know, these cancers can grow, slower, and sometimes they can grow super fast. So it depends a little bit on the situation. But I I do think that, you know, I I think making sure that you're able to, you know, check stuff off of the bucket list is always a very important thing in my, you know, opinion, knowing that these cancers, you know, we we don't think that we can necessarily cure somebody with all of these drugs. So what we're trying to do is delay, you know, the cancer and give people extra time. You know? So I think it's important to enjoy that time that, you know, extra time that somebody has. And and if that's very important to somebody, you know, checking off bucket list, you know, seeing family and friends or connecting up, I think that that's, a very important thing to do. Great. Thank you. This next question asks, if someone is being treated with bevacizumab, how long after being on the drug would they need to wait to have HIPEC surgery? You know, so that varies by surgeon. Oftentimes, the surgeons can be comfortable with certain amount, but, usually, it's probably at least, you know, four to six weeks often if if you're very if you can wait that long, it's probably the safest thing to do. One of the things about bevacizumab is it sticks around in the blood for quite some time. So I think, you know, I I think it depends on how urgently you need to have the surgery because sometimes you just need to go for surgery, whatever the surgery might be, you know, and you might still have that. But, you know, I think this the longer you wait, a little bit more safer it is that the effects of bevacizumab would not affect, you know, the outcomes of the surgery. Got it. This next question is interesting. So they mentioned that their mother's doctor, is not using, perhaps, a type of immunotherapy and instead using a less effective combination of chemotherapy drugs for treatment because they're not a meso veiling illness specialist. So the question asks, how can they address this to their doctor, the patient's doctor, about using a more effective combination of chemotherapy or perhaps convincing them to go see a mesothelioma specialist? That's a good question. I think that that can be, something that, you know, can be a little bit difficult to draw us, for sure depending on the situation. But I do think, you know, asking about, these treatments, that you hear about and kind of getting the response and seeing what the what the reasoning might be, you know, behind the choice of treatments would be very important because there may be some very important, information that is, leading someone to recommend one treatment versus the other. But the other thing that is, I think, getting a second opinion, you know, is always a a a potentially a good option, especially if you wanna be sure that you are getting the right treatment for, in the right situation. So I think it's, you know, always a great thing to potentially ask if you can go and get a second opinion. Yep. Absolutely. This person has a question about the pleurodesis surgery. Is it a surgery that's considered when talking about immunotherapy drugs, or is there any kind of relation between a pleurodesis and having immunotherapy? So so pleurodesis is a type of, situation where they're, actually infusing, and it depends on the particular thing that they're infusing. But they're infusing something to try to help with the the fluid, the effusions that can occur, based off of the mesothelioma. So generally not thought to be necessarily related or, for treatment purposes for the actual mesothelioma, but potentially to help with the side effects or this, the symptoms, basically, of the mesothelioma, filling up the lungs with the fluid. So often, thoracic surgeons might, put in, that do that type of procedure to try to help with that. So I I don't think it necessarily has anything to do with the, immunotherapy drugs, the treatment drugs. Right. The person who asked about, stopping chemotherapy due to, reaction, and what the next steps are after that case, has a follow-up question about whether, if scans are showing more evidence of mesothelioma after, rounds of chemotherapy but have to stop due to a reaction, then what's the next step? What if taking a break is a bit scary because the scans show that there's more evidence of cancer? Right. Yeah. That is a good question as well. I think, you know, if the scans are showing that perhaps the cancer is growing back quickly, You know, it may not be the the right thing to necessarily ask, you know, wanna to do a break. And they may think about, you know, potentially using other treatments like we talked about, either other chemotherapy, drugs, or perhaps using the immunotherapy combination if that has not been tried before. But, yeah, I think it it's every situation is different, but, definitely, if it's, coming back and perhaps the symptoms are coming back, you may need to be put on a different treatment. Right. Great advice. For this next question, they asked, is there a way I could send this webinar recording to my family to view later? And I can go ahead and answer that. Yes. In a few days, we'll be go ahead and sending out the, the recording of this webinar, and, you can share it to family, loved ones, caregivers, as you see fit. So, absolutely, you'll you'll be receiving a a recording of this webinar in a few days, if you're attending tonight. And, for the person who asked about, getting their mother's doctor convinced about, maybe changing up the treatment type or maybe convincing, your mother to go see a music video of a specialist. Maybe showing them this recording could help with that argument too. This next question here says, are the studies done that we talked about, for example, the CheckMate trial, are the studies done on immunotherapy, including pleural mesothelioma patients and peritoneal mesothelioma patients or just one or the other usually? So, yeah, so the CHAMPBEK study was specifically for pleural mesothelioma patients. And so so, again, you know, I think that that can be challenging, because peritoneal mesothelioma, you know, often does, you know, use the same drugs and often will be, kind of, we call it extrapolated or basically using the study results for pleural mesothelioma to expect that it would work for peritoneal mesothelioma as well. But, you know, it's pretty rare to have a, you know, a large trial like that and have both pleural and peritoneal mesothelioma patients represented. Yep. Great. Thank you. This next question asks, if someone already has arthritis, could immunotherapy make that worse? So the answer is yes. I have seen that quite a bit. You know? So it is something that, you gotta keep in mind. Yeah. As I mentioned, you know, sometimes the arthritis, it depends a little bit on, the reason for the arthritis. You know, there are, certain arthritis is that are considered autoimmune, like rheumatoid arthritis, then I think, you know, oftentimes that the the immunotherapy could potentially make that worse. You know? I think in general, I didn't mention this, but, you know, any patient with autoimmune, disorders, we do think twice about whether or not to give immunotherapy because I think the chances of, more severe side effects tend to be, higher. And so it depends on kind of, the type of autoimmune, disorder that somebody may have and whether how severe it might be, whether or not we would be, considering trying these medications or not. Right. Absolutely. Does immunotherapy also cause blood clots? So not particularly, known to cause blood clots by itself. You know? So I think blood clots are relatively, commonly seen, though, in any camp's active cancer. So, so we do see that commonly just in general. So it may not be the immunotherapy by itself, but it could just be the cancer, you know, that is increasing one's chance of developing a blood clot. Understand. Can immunotherapy kill good cells too like chemotherapy does? So, you know, I think I don't think that it's necessarily, the same type of mechanism. But, again, you know, like I said, it can affect some good cells because it can cause an autoimmune type of, a situation where it's kind of affecting your normal cells, because it's ramped up and kind of, going all over. So, you know, I think it can. You know, that's kind of what we think about. But in terms of actual killing, you know, it probably is affecting your normal cells, but normal cells are often, are able to kind of, kind of get better, you know, when the assault has gone away. So, usually, it's not, the same type of mechanism. Has there been any research on fasting before, during, or after treatment, especially chemotherapy, is a way to preserve the good cells? So I think that, that has I have not seen any large scale studies that have been able to show that that's been beneficial. Although, I you know, again, I think that there are, some people that are are very much, supportive of that approach. So I think that that is something that, some oncologists will, you know, agree to and some may not, based off of, the limited, like, large clinical type of trials that we recommendations on. Right. Thank you. Okay. For this next person, they said that they've had chemotherapy. They've had one chemotherapy treatment after ten sessions of immunotherapy. They were informed that it is quite common to go back and forth from one to the other. And while immunotherapy was a walk in the park, chemo is kicking them in their rear end. Is this normal or expected if they were fine on immunotherapy and are having trouble on chemotherapy? Yeah. Well, I I I would also say that I think chemotherapy tends to be a little bit harsher and, or, like, more people are gonna have side effects in general with, a chemotherapy than immunotherapy. So in general, I think that that's true. It's, you know, that, chemotherapy is a little bit tougher, you know, to get through. Oftentimes, a a a lot of the patients or majority of the patients will have side effects. It's just, you know, the severity of side effects may be very, different for every patient. But with immunotherapy, there are some patients that do extremely well, you know, and have very little side effects from immunotherapy and some, patients that have a lot of side effects. But kind of the majority of the patients probably have less side effects in general with immunotherapy, than if you compare it to chemotherapy. Got it. Thanks. For the u v one vaccine, which, as a reminder, is still under investigation, do you know if there's a benefit of the u v one vaccine for peritoneal mesothelioma patients as well as pleural? So I am not familiar whether or not they're looking at it for peritoneal mesothelioma as well. You know, we have very little information actually about, you know, the effectiveness of it and what, what the company is, looking at in terms of which type of cancers. So I think all we know is kind of from what has been reported, you know, through, a meeting and also, you know, the FDA report saying that it's fast track. So so I'll be interested to see, you know, where the development of that particular vaccine goes, whether or not it's something that will ultimately make it to the clinic or not. Are there specific treatments that tend to work better for peritoneal mesothelin with patients, I suppose, when it comes in regards to chemotherapy or immunotherapy? Tons of drugs like chemotherapy or immunotherapy. I don't know that, there's a whole lot of distinction between, you know, peritoneal and, pleural mesothelioma. Most, you know, folks will be will use, you know, all of the drugs, you know, for any of the mesothelioma. I think some of, you know, the other, treatment modalities that are nondrug related might be slightly different, obviously, for, pleural versus peritoneal mesothelioma. But I think the the, you know, the standard intravenous drugs, you know, I think, are used interchangeably. Right. And this next question asks if there's a big difference in chemotherapy treatments, in terms of where they're administered. So is there are there facilities specific to chemotherapy versus immunotherapy? So I I think that, most, oncology clinics should be able to have both chemotherapy and immunotherapy. They should be able to provide either choice. I don't think it's, specific to one particular clinic or the other. It's just, who is prescribing the drugs. Yeah. That's been my experience too. And, again, as doctor Suga mentioned, they're both given intravenously. So as long as the cancer clinic, is set up to administer IV drugs, there's a good chance that they'd be able to, prescribe and administer both types of treatments. This is an an interesting question. Someone asked if there's any advantage to therapy for DIM mesothelioma, which if people don't know is diffuse intrapulmonary mesothelioma, which can, invade the inside of the lung, which is a bit abnormal for mesothelioma. So is there are there therapies that we discussed today that would be beneficial for someone with DIM mesothelioma? That's a great question, and I don't think that we have enough, data to be able to say one particular treatment is going to be, more advantageous for that particular type of mesothelioma than others. Yep. I think there's gonna be need to be more research with mesothelioma already because of this disease. Yeah. Yeah. So a lot of it, you know, may just be, you know, reports, you know, of of patients, you know, that have that and whether or not it's, it the the treatments are working or not. So Yep. Absolutely. Someone says they're on Keytruda and have had some side effects, in the past, but at the moment, they're not having any. What are the chances that some of those side effects could come back? Yeah. You know, it can go away and come back, but I think it's great to hear that the camp the the treat the side effects have gone away, and, hopefully, they won't come back. Sometimes other side effects pop up, you know, like, not the same side effects, but different side effects, but also cause the inflammation somewhere else. So, you know, it's, it's unpredictable, again, with immunotherapy when they pop up and where they pop up. So that's kind of the challenge a little bit because sometimes if, you know, physicians or, you know, like, ER physicians and things like that or, you know, if they see patients, they may not necessarily recognize that that that could be a side effect from drugs like immunotherapy. So a lot of education. Yeah. Just a couple questions left here for the night. This person asked, my mom is on a clinical trial of immunotherapy and chemotherapy together for epithelioid peritoneal mesothelioma. Can they do just chemotherapy or immunotherapy in the future, or will they be ineligible because of the combination during this clinical trial? So I think, it depends a little bit. I think the chemotherapy and immunotherapy, you probably wouldn't necessarily wanna use the exact same drug, you know, in the future, you know, if, know that the cancer grew, say, on both the chemotherapy and the immunotherapy combination together. But as I mentioned, you know, there are other chemotherapies that work in different ways that potentially, you know, someone could, you know, potentially use or perhaps, you know, there may be other immunotherapies that haven't been used in that situation that could be, used in the future. So I do think that there may be some additional options down the road. It just may not be the exact same drugs. Mhmm. Perfect. There's a couple questions here about eligibility. So I'll I'll kind of combine them. But, how do doctors tell if immunotherapy or chemo will be better for a patient? So kind of what what makes a good candidate for immuno versus chemo, and is there anything that would prevent someone from having either option? Yeah. I think that, you know, a lot of it depends on some of the situations that I kind of, outlined, but, like, depending on the type of mesothelioma, you know, you might wanna favor one versus the other. Also, you know, I I do think in general, you know, how, you know, some of the medical, conditions from the past, you know, whether or not, you would be a candidate for immunotherapy or chemotherapy could be different. So I I think that a lot of oncologists will think about that as well, you know, whether or not chemotherapy tends to be a little bit harsher on the body. You know? So perhaps, you know, that might not be as good, you know, if you're starting off very weak in a weakened state, so something like that. Immunotherapy. I think in general, most people would qualify. Again, I and do mention that, you know, maybe the autoimmune, you know, you might think about it whether you want to try that, because you might have a higher risk of developing side effects. I think, if somebody, had a transplant, immunotherapy is really kind of scary to use actually for, so usually not, considered candidates in those situations. Thank you so much. And then another question here. What do you typically suggest as a first line treatment for epithelioid patients, chemotherapy or immunotherapy? Yeah. So, you know, I went over the data, and that's the data that we have. And so I do think that I have a very long conversation with patients about, both options and kind of the pros and cons of both options and which one they would like to, you know, start with first. Because I don't think, it's a one size fits all for that particular situation. I think for epithelioid, you can absolutely start with either approach, and I think they would be appropriate, you know, whichever approach, is chosen. And you always have the option or fall back to try the other approach, if it stops working. Great. We've had so much interest in tonight's webinar. So I have just a couple more questions here. People are are getting in, under the wire. So this next one here says, would you recommend any specific chemotherapy or immunotherapy medications over surgery? And I would add maybe how would you what's your take on, maybe combining chemotherapy or immunotherapy with surgery versus oversurgery? Yeah. So, you know, I think, there is, an approach to use a utilized surgery, you know, as well, in some patients. I I do think that, it's reserved for, you know, kind of a set of patients, you know, that might be able to handle a surgery, like, that is a relatively, major surgery that we are talking about. You know? And I think that surgery has become a little bit more controversial whether or not it, you know, how effective it is, you know, in mesothelioma. But I do think there's select patients that would benefit from surgery, you know, as long as it's done in, a center that has high high volume and a surgeon that is very comfortable doing that type of surgery. And I think that if you do, get recommended surgery, then I do think using chemotherapy or immunotherapy either before or afterwards would be a consideration. In general, I think right now, there's a little bit more data on using chemotherapy before or after surgery. And so I think, I generally lean towards using chemotherapy versus immunotherapy. Immunotherapy can some especially if it's given prior to surgery. I think right now it's in the, research space and the clinical trial space because it can sometimes, make the surgery maybe slightly more challenging. And so, you know, there is kind of effects that could happen with the surgery if you give immunotherapy before surgery, but it has been done. So it is is not necessarily contraindicated to do so. It just should be probably done, either in a a specialized center or, you know, in, in the context of a trial. Right. Absolutely. It's it's been interesting to follow those those studies about when the best timing is for immunotherapy, before or after surgery. Because like you said, in in certain cases, it may benefit the patients, and in others, it may not depending on how soon and how much you give to people beforehand and the based on the type of cancer they have. So very, very unique and situational, and I think, we're still trying to figure out what the best case is for using those. So the last question here for you tonight, doctor Suga, is what is the treatment timeline of chemotherapy versus immunotherapy? I think most people know chemotherapy is maybe given in cycles about every three to four weeks. So what does that look like, between the two? Yeah. So I I think that's that is a unique aspect, I think, of chemotherapy versus immunotherapy. Generally speaking, chemotherapy, as I mentioned, is kind of in a a a finite timeline. So, usually, you give, the CompSafe, you do the combination that we talked about, the platinum and amitrexed combination. You give it once every three weeks, for four to six cycles, and then you give a break. And then you kind of monitor and see, you know, what happens with the cancer. Hopefully, you see shrinkage in in between those that time. And then for immunotherapy, though, oftentimes, it's given, you know, every couple weeks, in general, depending on which treatment you're getting, maybe every two or every three weeks. But it's also, given, you know, kind of, as long as it seems like it's working. So there's usually not necessarily a pre, specified stop date, you know, for the immunotherapy treatments. And so often you will continue as long as you think that, there's continued benefits. So, you know, scans, you know, in between, every couple of several months, you know, is something that is commonly done to kind of look to see whether or not you're still benefiting from the treatments or if you need to think about a change in treatments. Right. Absolutely. Well, thank you so much, doctor Suga. That just about wraps us up. I do want to take a moment to share my contact information. If you have any additional questions, don't hesitate to send them over. In addition to the contact information you see on the screen, you're also welcome to respond to any of the emails that we've sent leading up to tonight's webinar. And you can ask either myself or doctor Suga any questions, and we'll make sure they get to the right person. As I mentioned at the beginning of tonight's event, if you have a specific medical question, we encourage you to speak with a mesothelioma or a lung cancer specialist. Over the next week, you'll receive a couple more emails from us. The first one will contain the recording of the webinar along with related resources, and the second will contain a survey asking for your feedback about tonight's event. With that, I wanna thank you all for attending this evening. Thank you, doctor Suga, for a wonderful presentation. And as always, if there's anything we can do to help, please don't hesitate to ask. Thanks, everyone. Have a good night. So much.