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View the full CURE® Educated Patient® Webinar: Testing and Treatment for Non-Small Cell Lung Cancer on demand.
Kristie Kahl: Hi everyone. And welcome to today’s live broadcast, the Educated Patient Webinars: Testing and Treatment for Non-Small Cell Lung Cancer. I’m Kristie Kahl, vice president of content of CURE. We are pleased to bring you this webcast presented by CURE and sponsored by Regeneron. We have a few important announcements before we begin. We'd encourage you to ask questions during the event which you can submit by typing them in the Q&A box. You'll be receiving a survey via email tomorrow. As a thank you for watching the full webinar and completing the survey, you'll be entered to win a Visa gift card. We're pleased to be joined today by our moderator, Dr. Roy Herbst, Ensign Professor of Medicine and Professor of Pharmacology; Director of the Cancer Center for Thoracic Cancers; Chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital; as well as Associate Cancer Center Director of Translational Science at Yale School of Medicine. He'll be joined by Dr. Chaitali Nangia, Associate Professor of the Hematology & Oncology Division at Hoag Cancer Center Irvine; Beth Sandy, a Nurse Practitioner of Thoracic Medical Oncology at Abramson Cancer Center at the University of Pennsylvania; and Isabella De La Houssaye, a patient advocate. Thank you for joining us today and I'll now pass things off to our moderator to begin the discussion.
Dr. Roy Herbst: Thank you very much, it's really a pleasure to be here today. And we're all here. It's lung cancer awareness month, so it's a very good time to talk about lung cancer and the many things we're doing. Why don't we just start by having everyone tell them just a little bit about their background and why they're here today. Do you want to start, Isabella?
Isabella de la Houssaye: Sure. I am – I was diagnosed with stage IV non-small cell lung cancer EGFR+ in February 2018. And the testing, the biomarker testing has been a huge part of my treatment over the past four years. And so I'm here to share my experiences.
Dr. Roy Herbst: Great. And Chaitali?
Dr. Chaitali Nangia: Yeah. Hi, there. I'm Chaitali Nangia, a medical oncologist. I'm involved a lot with research in lung cancer, especially in the immuno oncology space and run a bunch of clinical trials, especially in this targeted therapy space and have been involved in lung cancer story for quite some time.
Dr. Roy Herbst: Great. And then Beth?
Beth Sandy, CRNP: Yeah, I'm Beth Sandy. I'm a nurse practitioner in the cancer center at the University of Pennsylvania in Philadelphia. And my practice is lung cancer and have been doing that about 20 years as a nurse practitioner.
Dr. Roy Herbst: I'm Roy Herbst, I'm a medical oncologist, here at Yale Cancer Center, Smilow Cancer Hospital. I lead the lung cancer disease center, and also the chief of oncology. I'm happy to be your moderator tonight. OK, glad you're all here. Let's talk about biomarkers. So the first thing is why is it important, Chaitali, to have biomarker testing before treating for lung cancer?
Dr. Chaitali Nangia: [00:03:00] Yes, I think just to kind of take a deeper dive into this, I think biomarkers, what we're trying to see is when you get diagnosed with lung cancer, we want to do more personalized treatments. We want to give you therapy that's going to spare you more toxicity and hopefully spare you chemotherapy and get more targeted drugs. And so the step one is to recognize which are the patients who are going to benefit from this therapy and how do we best decide which patients should get a combination approach or should get just immunotherapy or like in Isabella's case, get a targeted drug. So it starts by testing. And nowadays, these testing have become quite sophisticated. You can do it either in the tissue or you can do it in just a blood draw. And that helps guide the physicians to see what would be the best first line therapy or what should we start out with to give you the best outcome, both in the short run and in the long run, because it makes a difference with what you got started with.
Dr. Roy Herbst: Absolutely. And Isabella as a patient, what do you understand about this? This is precision medicine, the right drug for the right person at the right time. But how much did you understand about this when you started your care? And how has that evolved?
Isabella de la Houssaye: I didn't understand anything. And what was quite frightening as a patient who was stage IV and declining rapidly was how long it took to process the information. And I had the tissue biopsy and that took almost a month, and I didn't understand what's – can't we just start treating? Why do I have wait? And at the end of the day, I did a blood biopsy and things moved more quickly because then they could recognize that I was EGFR+ and I was able to start a TKI more quickly. But it was – I didn't understand it, I have come to understand it. And in my kind of cancer, EGFR+, it's important to have the biomarker testing after every bit of progression to see how the cancer's evolving because it does change overtime as it gets treated.
Dr. Roy Herbst: Right, that's well said. I've seen biomarker testing evolved when I first started working in this field in 1993-94, and then we didn't even get biopsies sometimes. And now, of course, the first EGFR inhibitor trials, I remember leading some of those when I was in the Anderson in Houston, 1996-97. It's amazing that now, you are now most advanced generation drugs and you've found those drugs and you're treated. So Beth, as an advanced care provider and working in the clinic, how do you work with the patients when they come in, they knew diagnosis of this disease, they're going to have to get a biopsy, sometimes it's needles, sometimes it's liquid, how do you educate them as to what's going on?
Beth Sandy: Yeah, I think that's really complex sometimes. There's a whole lot of different things that can happen here. Number one, you're telling them, "I'd really like to wait for these results until we start treatment." And no one wants to wait, you want to get treated right away. So [00:06:00] this idea of waiting for the results to come back can be really hard, but it is really important that we know these results. To Isabella's point, we'd like to do it, both the blood and tissue because the blood comes back faster. If it's negative, we do like to wait for the tissue, if we can, depending on if we have enough of it. So these are all things that I end up explaining to patients that we're going to wait for these results until we start therapy. And we may start therapy and then test again later depending on the circumstances. Maybe we didn't have enough tissue, and our test results were inconclusive. The thing I would say is that I want patients to be advocates for themselves, make sure that you are being tested, if you have non-small cell lung cancer, especially a non-squamous type, the most common is adenocarcinoma. Because, really, everyone in that category should have a full biomarker panel done.
Dr. Roy Herbst: Absolutely. We're getting some questions from the audience. And we're so happy to have a live audience tonight. Here's a question. At this point, is biomarker testing standard of care in cancer centers for non-small lung cancer, I felt a lot of resistance about this with my mom's diagnosis. Sherry Baker points out. Chaitali, is it standard of care, you're in Hoag, that's – you're in California, you're in Southern California?
Dr. Chaitali Nangia: It's pretty much standard of care. Especially if we're talking about advanced lung cancer patients, it's definitely standard of care. Even in early stages now, we pretty much want to know because of the role of neoadjuvant/adjuvant, that means do need treatment before definitive surgeries. It's becoming standard of care. So pretty much in your first visit when you see your provider, you should be drawn for the liquid and tissue be submitted.
Dr. Roy Herbst: Isabella, you have some thoughts on this.
Isabella de la Houssaye: I do. What I see in my face group book, a group of people with non-small cell is that the operative board is in a cancer center, and so many people are not treated. And in the first instance, we've been, at any point, in a true cancer center, and they're being treated by the local doctors, local oncologists. And actually, they're not being – the biomarker testing is not widely used in a lot of places, even in the United States. And so, unless you're treated at a cancer center, you may not be getting that.
Dr. Roy Herbst: Right. I think that's, unfortunately, it is true. Some people don't get to set into have the test done. There's also a lot of disparities in the care of patients around the United States, sadly. People that don't ever get advised to have the test or from under representative minority groups. And it's really a shame because as you've told us, Isabella, these drugs do work when you're matching their – you say they're more specific and less toxic, because you're matching the drug with the biomarker, right?
Isabella de la Houssaye: Right.
Dr. Roy Herbst: [00:09:00] Excellent. And then Beth, your perspective on this. You're at Penn, I know Isabella's in New Haven, we better do the biomarker testing at my place, so I'll have to – the heads will roll here. But, Beth, what's happening at Penn, you and Dr. [INAUDIBLE] team there?
Beth Sandy: Yeah, it's absolutely standard of care at the University of Penn. But exactly what Isabella said. I talked to some of colleagues around the country and it may not be done everywhere. There used to be, years ago, this thought, "It's mainly in the non-smoker, so we're just going to test them." But that's not true, really. And the majority of the newer biomarkers that we know about are more common actually in smokers. So it doesn't matter whether you're a smoker or non-smoker, everyone needs to be tested for these biomarkers. Because like you said, Dr. Herbst, if you don't find it, you can't actually use the targeted drug to manage that, which will work best for the cancer.
Dr. Roy Herbst: We're on the CURE webinar now. And Isabella, how important your advocacy that works like this? So patients are watching, I'm sure, you said, face group, so you have a group that you're online with. Do patients talk and advocates talk and advise people? At least someone in that room is asking about biomarkers, it's the physicians or the advanced care provider or one of the nurses does it, as suggested. And hopefully the patient will ask about it, right?
Isabella de la Houssaye: Right. One of the things that with lung cancer and particularly biomarker testing is it's so individualized that it's actually more effective when you break into groups that are specific to the different biomarkers, because then patients can relate better and ask more relevant questions. So that's why I tend to go to the Facebook group more, because it's an EGFR specific, there are RAS specific and ALK specific groups as well. And organizations, like CURE, are awesome. There are resources, but I find the most effective are when they break into specific to my kind of cancer or within kinds of cancer.
Dr. Roy Herbst: Got it. Chaitali, there's a question here. How much more effective is tissue biomarker than blood biomarker? Do you do one, the other or both?
Dr. Chaitali Nangia: If you look at the data, the liquid, which is the blood biomarkers, quite specific. So that means that if it's positive, it truly is positive, sometimes we debate the question, could it miss a task? Or could it falsely be negative that you actually have it, it's just not shedding it in the bloodstream? So I think a tissue is the gold standard, but liquid is pretty close to it. And it's more easy to do, easy to navigate through, so I think that's how it plays was if I get my answer in the liquid? Then yeah, the tissue can [INAUDIBLE] but if I don't get my answer, if it's negative, I shouldn't always assume that that would be the case in the tissue, if that answers your [00:12:00] question.
Dr. Roy Herbst: Absolutely, and I would agree. We had a good first discussion, let's move on to another topic. Topic two, understanding the results. It's one thing to do the testing but then you've got to understand what to do, so some patients apparently are overwhelmed by the results. How do we work with the team? How does the teamwork with the patient understand it? So I'll start with you, Chaitali, again. And that you get the result back, how does your office work with the patient? How do you work with a patient? Could you explain to them what it means and what needs to be done?
Dr. Chaitali Nangia: For me, anytime is a – when you're just starting out your journey, there's a lot of apprehension, there's a lot of confusion, there's so much information. It's always difficult to sought out for the non-medical people. Even for us, it's difficult. So I like to invite the family, the caregivers and the patient to come and definitely for the subsequent needing when I have the results to go over. Because it really is a team effort, it's not just one person doing it, it's not even just the patient and the provider doing it, it's the whole care of team that needs to be involved in it. And as you know, that once after 10 minutes, the patients, what I always teach my followers, they stop listening, it's too much for them. So if they have more family members with them, then hopefully everybody [INAUDIBLE] there's a piece of that information. So I like to work it as a team approach. Obviously, from our side, we will always have our entire team present in that meeting as well.
Dr. Roy Herbst: What's your experience, Isabella, with this?
Isabella de la Houssaye: It's complicated. I know in my own, my own understanding has grown tremendously over the past four years and what I thought I understood at the beginning. I've – that's evolved tremendously. And that's why – and your time with your care team can be limited, so I think there's a huge role for support organizations to help patients in this area.
Dr. Roy Herbst: Thanks. Another question. Patients, Beth, might ask you. Is there additional information, other sources where I can go to to learn more about these biomarkers, what they mean? What do you tell them?
Beth Sandy: I think that's hard, because there are some sites that will give complex information. There's a website that I use a lot called mycancergenome.com. And you can look at your molecular pathology report and type in whatever it says there, and it will give you an explanation. But a lot of times, that explanation is in medical terms, and that can be hard for a patient who doesn't understand the terminology. So I think going back to what Isabella said, is that a lot of times, look – going to online support groups is maybe sometimes a better way to get more down to earth information. That being said, I would ask your care provider, ask your nurse, ask your doctor, because it's really our responsibility [00:15:00] to relay that information to patients in an understandable way, in a way that they understand what is happening and what we're going to use to treat their cancer based on that report, or what we're not going to use, based on that report. So, unfortunately, it is complex like Isabella said, so there's not really an easy place to go online that'll spell it out in layman's terms for you. So I still think going back to your care of team and saying, "I really don't understand what K-RAS G12D means, as oppose to K-RAS G12C." And let us explain that to you.
Dr. Roy Herbst: Great. OK, we have tons of questions here. Anyone can take it, first one to hit the buzzer. If a patient doesn't feel the care of team is adequately informing them about the results or they weren't even referred to get tested, what advice do we have for those patients? Who wants to take that one first? I'm going to ask you all, but – Isabella?
Isabella de la Houssaye: I'll just say I would tell anybody, no matter how great your care of team is, to get a second opinion no matter what. And I've found that very helpful and sometimes, it's the same sort of answer but explained differently, but I think it's just very important sometimes to hear from different people on the same topic when your health is involved.
Dr. Roy Herbst: Chaitali?
Dr. Chaitali Nangia: I think I agree with Isabella. It's nothing – I agree that patients should get a second opinion because it also tells them, reassures them that this is how the whole medical community is answering them. But obviously, the catch being, what if you don't hear exactly the same thing? So you have to be kind of know that before you go in, that you will be emotionally OK handling that kind of information, because there's certain places that are standard of care, this is how we do it. But then there's definitely gray zones and complex patients that it can be done more than one way. So I just want my patients to be aware of that. And then, depending on which provider you're seeing, you may have clinical trials that may be completely different at two different providers. So you also want to see which one would you want to go with. But no, I think it's good to hear, especially if it's standard of care.
Dr. Roy Herbst: Right. Beth, someone asks, is it better to have a mutation discover than finding them? If no mutation is standard chemo than better than targeted therapy?
Beth Sandy: Yes, I think, there's no right answer here. So I wouldn't necessarily say it's better to have one thing or the other. It's better to know what you have and then treat appropriately. So if you have a mutation but you don't know it because you were never tested for it, and we go straight to immunotherapy, it's probably not going to work very well for you, because your cancer's driven by that mutation and we should [00:18:00] be treating you based on that. And the vice versa the same. If somebody has a mutation, we need to know about it so we don't start them on the wrong therapy. So depending on certain mutations, sometimes it's better to have one that responds very, very well, so that may be better prognostically. But now in the era of immunotherapy, my goodness, we see patients living years and years with immunotherapy, so I don't necessarily think it's better or not, it just guides our therapy. So what's not good is to not know. Because then, we don't – it's like we're just going to throw this out there and hoping it works.
Dr. Roy Herbst: Exactly.
Dr. Chaitali Nangia: And if I may add, the way the field is progressing, because today, liquid doesn't show blood, the chances are a fast forward [INAUDIBLE] Even that blood will show mutations, it's just how the technology's progressing and how the drugs that we can use for targeting is progressing.
Dr. Roy Herbst: Exactly. We have a lot of questions now, people are asking about minimal residual disease, meaning when you know if you've had enough therapy, do blood tests help? They're also asking about resistance. A couple of stories here in the chat, where patients get these drugs and then they become resistant, what do you do next? I guess that's something everyone has a perspective on this, why don't we start with Beth this time?
Beth Sandy: Yeah, so you can – and I would advocate for if their cancer is worsening to test for resistance mutations. For certain things, we have treatments or even mostly clinical trials to evaluate for this. So I would definitely recommend re-testing at that point. I would also maybe even recommend if the first time around, you didn't have a mutation. You do your standard treatment, then the cancer's worsening, maybe consider re-testing at that point. Especially if the original tissue was not sufficient, that didn't mean that you don't have one, it just means we didn't have enough tissue in order to do it. This is where the liquid biopsy comes in really handy, because then we don't have to go in with a needle and do an invasive procedure, we can just send a blood test off. And I know someone asked the question, is there a gold standard for which company? I don't really think so, I think there's a few out there, a handful, that we use a lot. I'm going to refrain from making suggestions about different companies, but I think there's a handful that or have very good reputations, that generally, we use.
Dr. Roy Herbst: Great, any other comments here?
Dr. Chaitali Nangia: I think this is a very active area of academic interest because we've seen that if you stopped with certain drugs, you get resistant to that medication. The question rises, what's the next best therapy? And what best to combine it with, and then sometimes the resistance matters with what you're starting out with, for example, if you take a case of EGFR, which is a kind of bio-marker and depending on what resistance you may have either at the get-go or subsequently, they may be in the same tree different branches that you should get as a treatment, and even in the space of [INAUDIBLE] and all this now there are so many clinical trials that are trying to address resistance mechanisms and how best to overcome them, so I think if you've not had a clinical trial opportunity at the first line while we're talking, consider that as second line that means you progressed on first line treatment to see if you can better understand that.
Dr. Roy Herbst: Very good, let's move on to another – Isabella, sorry.
Isabella de la Houssaye: Sure, I would – so I get a blood biopsy quarterly and it tells me how well the current treatment I'm working – I'm on is working, so that for me at least the mutations don't show up if the treatments are working and they begin to show up when they're not, and sometimes that gives me a heads-up before tumors progress, which is good information to have, otherwise people tend, in my world of EGFR, to get bio-marker testing every time you have progression to see what new mutations might have evolved and how that affects treatment and the other ways in terms of trials that they're using it in my community is to see whether – rather than put someone on a tough treatment and test and not know whether it's working safe for three months a blood biopsy might be able to show you in six weeks or three weeks even whether or not you're responding to that, so it can help patients determine treatments more effectively.
Dr. Roy Herbst: Absolutely, guide the therapy with bio-marker testing, so before we move on to the next section, someone has asked us why isn't everyone tested? What do you think?
Dr. Chaitali Nangia: I think that's an access to care, it depends on way you practicing, it depends on how fast you can get those turnaround tests, what the institutional practice may be, but I think it's pretty standard of care, it's covered by most insurances if done at the right indication, so it should be really, I think there's a big push to make it almost universal for the right settings.
Beth Sandy: I will say we don't test small cell lung cancer routinely because we don't generally find these bio-markers there, and at my institution we don't routinely test squamous non-small cell lung cancer because again the majority of these bio-marker question – or these bio-marker results are not found in those patients, that being said, I would test certainly squamous patients that particularly have a [00:24:00] characteristic like being a never smoker, something like that. Doctor Herbst, I would throw that back to you, do you test all non-small cell patients, or do you test the majority of non-squamous, which are predominantly at no carcinoma, what are your thoughts on that?
Dr. Roy Herbst: Well, I happen to believe you should test all non-small cell lung cancer patients, because even if it's not read as an ano-carcinoma, it can have mixed features, or it could be missed read, so we try – you should get it covered to test all patients with a diagnosis of non-small cell lung cancer, small cell I would agree with you, I think the bio-markers, think like the PDL1, which we're about to get to in a moment, but we probably wouldn't be – the actual indications there are still quite rare. Let's move on the next section, which is different options based on PDL1, very nice question Beth, you led us into the next section. First question: do we have any indication of how often PDL1 is expressed in patients with lung cancer, specifically non-small, if so what can we share about that information? So PDL1 is actually compared to the testing we give [INAUDIBLE] actually pretty easy to get, you actually get it back much quicker, how often is PDL1 expressed in lung cancer, Chaitali?
Dr. Chaitali Nangia: I would – again this is where the smoker, non-smoker matters. So most of the – if you take the smoker population that percentage is definitely higher than patients who are never smokers, so that percentage is lower than never smokers, in the smoking population it can vary depending whichever data set you're looking at anywhere from 40 to 60 percent, never smokers that percentage is lower in my experience.
Dr. Roy Herbst: What do you think, Beth?
Beth Sandy: So it's about – I use the 30 30 30 rule, or I guess 33 33 33, so about 33 percent of patients will be negative, PDL1 expression of zero, about 33 percent will have a low expression, which we will consider one to 50, and about 33 percent will have a high expression of 50 percent or greater, and that can predict in the stage four setting at least, for response to certain immunotherapy drugs, but it's not a perfect bio-marker, I want to hold up there, it can be predictive to some degree, but even if you're negative for PDL1, we're still most of the time going to use immunotherapy if you do not have a positive bio-marker, so we like to look at it, it's a predictor, but it's not 100 percent, and I have seen patients with no expression respond to immunotherapy along with chemotherapy, probably better than what they would have with chemotherapy alone. Doctor Herbst, what is your experience with PDL1 as an – as the way you guide your therapy?
Dr. Roy Herbst: Well, [00:27:00] it's a very important – first of all, let me just say if someone has one of the actionable mutations, that we've just been talking about, I would usually treat with a drug, and we were talking – Isabella you talked about EGFR, but of course we have ALC and RAS1 and RET and MET and INTRECT and RAS, we have a whole bunch of targets, and if someone doesn't have any of those, I use PDL1 to help me. If PDL1 is greater than 50 percent, meaning more than half the tumor cells are positive for this marker, I would recommend immunotherapy alone, and there you have a chance of more – about 50 percent, the tumor will respond without chemotherapy. If the PDL1 is less than 50 percent but greater than one percent, then intermediate rank, I would probably use immunotherapy and chemotherapy combination of some sort, and then if it's less than one percent, which again I think Beth's numbers are about right, I'd probably use chemotherapy and immunotherapy as well, in some cases, we might use two immunotherapy drugs together, it really varies, I would ask Chaitali to talk a little bit about how she does this.
Dr. Chaitali Nangia: Yes, I think I agree with the general messaging, so PD1 testing has gone through significant evolution, the way we tested has involved significantly, which is why it's not a near perfect bio-marker but that's the best we got right now, and what we do is we can't use a PD1 to give us prognosis of the patient, that, oh, if you're PD1 positive, you going to live an x amount of time, and if you're negative you're going to live an x amount of time, but what it does have us speak of is what therapy would work best for you? And what combination of drugs would work best for you, so say there's PD1 comes back as 100 percent, I'm just making it up right now, so we know now these are patients that if you’re so immunogenic with this PD1 testing, that maybe you'll be OK with just a single drug checkpoint and the better and this many takers in that class of drugs, and you'll do just fine and maybe you don't need chemo, whereas if you are now in that really, really lower expression and you literally made the cut on the negative, now it would be foolhardy to just hang on head-on, the immunotherapy and maybe at this time you want to do a combination approach with the chemo and immunotherapy, so I think it's very important to make treatment decisions, I think you always have to have that carrier that is still improving, and it's not near perfect bio-marker, we also like Beth said, we have people who respond when they're negative and we then have people who don't respond as well as we expect them to even if they are positive, so I'm sure as the field evolves so would the bio-marker but at this point PD1 is important for decision making.
Dr. Roy Herbst: Absolutely, absolutely. What do you think, Isabella, you discussed this in your Facebook?
Isabella da la Houssaye: We do indeed, [00:30:00] and I just two thoughts to share, an EGFR, the – even if you have a high PDL1, immunotherapy still don't work so I guess that's a question back to you if you think there's progress being made on that or what the current state of the medicine is on that, that's a question, but the other comment I would make is you see in places where people are being are being treated, not in cancer centers, but where they have enough sophistication to be looking at these markers, they don't actually – sometimes they combine a TKI with an immunotherapy, which can be very dangerous for patients, and it's amazing to me how many times you see this happening, and people developing [meningitis] reactions, and that's just about education to your caregivers and your patients.
Dr. Roy Herbst: It's very tricky because you would think that you could use a TKI and immunotherapy together, but you're absolutely right, in patients that have the mutations, that would result in using one of these oral agents, the immunotherapy doesn't usually work that well, but even more importantly, by using the immunotherapy with the targeted therapy, you run the risk that you'll have increased what you call auto-immunity, inflammation of the skin in the lungs, in the GI tract, resulting in loose stool, it's a very significant extent, so it's very important that you think about how you do this, so if someone – so if you started TKI, if you started on oral targeted therapy, you've got to wait awhile before you can start the immunotherapy, even if you used it in a patient who really didn't have the right mutation because you don't – you have an overlap of those two agents. So you say that very well, I'll just say that we're probably entering a period now, where we have to start to personalize the immunotherapy. I can tell you having seen this for over 25 years, immunotherapy is just amazing how well it works in some people, but we have to figure how to make it work in all people and one of the things I've noticed is right now I mentioned the PDL1, that's all we really have right now to personalize the immunotherapy, but there are obviously other factors as well, because even though you have high PDL1 in some tumors, only half of them really benefit, so what about that other half? And then we also know that resistance can develop when you give immunotherapy, so one of the challenges for all of us is going to be as a community to figure out how to better and identify the other mechanisms of resistance there, but it certainly means that patients should go to centers where they can get testing done, you said something very interesting, Isabella, some patients have high PDL1 and they have high EGFR mutation, that's because the mutation actually results in the production of more PDL1, it's not an indicator that immunotherapy is going to work, so this is why we have to communicate, we have to educate, and we have to do programs like [00:33:00] [INAUDIBLE]. Any final thoughts on this section before I move on to the next? Beth?
Beth Sandy: I know somebody asked when you test for PDL1. Doctor Herbst, what are your thoughts on that. I mean, we would test certainly a diagnosis, do you feel that there's utility in testing after treatment?
Dr. Roy Herbst: I would do it at diagnosis, there are some thoughts now, for example we use immunotherapy in stage three lung cancer where people have had chemotherapy and radiation, and then we add the drug duromine for example, and it's possible that maybe the PDL1 status changes after you've treated the tumor, the cancer with the immunotherapy and radiation, so there are some research practices such as here at Yale going on to look at how does the immune environment change, but I would say do it at the get-go right at the beginning. At our place, we see a tumor board, when we first hear about a new patient diagnosis because it's done as a routine.
Dr. Chaitali Nangia: If I may add one more line to that, my thought on that would be for the general audience, when you have these bio-markers or mutations, you may have one that will think either you have it or you don't have it, that's how the cancers are, but then you have these type of mutations, these bio-markers, that are dynamic that change as the tumor progresses or whatever is happening in this tumor micro environment or the house of the tumor like Doctor Herbst said there's sometimes like populations who have undergone radiation maybe can up the PD1 level, similarly not a lot of like trust and looking at other ways to actually up the PD1 level, so for me I would definitely do it at the get-go and maybe go through a few lines of therapy, but if I'm in trouble I do check is again to see did things change because PD1 is not one of those mutations that either you just have it or you never have it, it can change.
Dr. Roy Herbst: Absolutely, so Isabella, as a patient, all this research, does that give you hope and how do your fellow patients feel about how that's going on?
Isabella de la Houssaye: It's all very exciting, a lot of us are part of the research, I was in a till trial earlier this year so I've – I feel like I'm a part of this cutting edge, how do we get immunotherapy to work in this EGFR world, so it's all very exciting and it does give us hope.
Dr. Roy Herbst: What about you, Beth? Do you guys run clinical trials in that small hospital in Philadelphia?
Beth Sandy: Yes, you mean that IVY League one, University of Penn? My fellow Yalester? So yes, we absolutely have lots of clinical trials, this is such an exciting time in lung cancer. Here we are, with all these clinical trials and looking at combining different immunotherapy mechanisms together [00:36:00] and then combining those with chemo, it's just a really exciting time, so yes, absolutely. Very exciting for all the different clinical trials.
Dr. Roy Herbst: What about you Chaitali, you running crowds out there in beautiful California?
Dr. Chaitali Nangia: Absolutely, I think our striving goal, my personal striving goal, is any patient walking in the door, should have a clinical trial, now clinical trial op is not for every patient and not all patients choose to undergo clinical trials, but that option needs to be there.
Dr. Roy Herbst: I agree, and the clinical trials of today are the standard drugs of tomorrow, and Isabella, your thoughts, you've obviously been on some trials? [CROSSTALK]
Isabella de la Houssaye: I just want to – I have been, our actually, so one thing though that is happening in my world as immunotherapies are introduced is that it's excluding people from TKI trials, and I think that's something as you all organize and conduct the trials that it's very important for patients to understand going into the trial what may or may not be available to them after the trial, and it's an evolving area, but I just pointed out, something to consider.
Dr. Roy Herbst: Well, let's move on, we have one more section, and then we're going to have some open discussion, we have many questions and I am recording them and we'll ask a few of them, we've already asked some, and it's about – now we're going to talk about the role of the caregiver in the entire journey, so what are some of the important things that someone looks for in a caregiver, someone who has cancer, and we have it from three perspectives here, and I'm sure everyone has multiple perspectives perhaps, but Isabella, caregiver, and having a support group, how important is that?
Isabella de la Houssaye: So I'll say it depends – I've had different places in my disease experience, so there have been places where I literally had to have help getting out of bed, walking, feeding, and that's a certain kind of caregiver, and then you also need help with the patient advocacy part, and sometimes those are not the same people, sometimes it's not possible for one person to play both of those roles, and I think that it's important to have conversations as a patient with the people around you, and figure out who can take on – it's very important to have someone with you in the doctors' appointments and hearing what's being said and having someone to take the information, but it's also important just to have the care that you need when you're not well at home.
Dr. Roy Herbst: Right, Beth, you've seen a lot of patients and caregivers, and how does that work, I guess it always helps to have someone else there with the patient as you're talking about the disease and potential side effects and how to manage it?
Beth Sandy: Yes, it's incredibly helpful to have a caregiver there, at least one. I think to what Isabella's point [00:39:00] is exactly right, the burden on the caregiver is huge, because not only are they trying to be there for the patient and help the patient physically and emotionally, but they're also trying to be an advocate and try to figure out should I be researching this, and trying to get the best for my loved one, and there's so much that goes into it and I think it's so hard for the caregivers, my heart really goes out to all the caregivers, whether you're a mother or father, a brother or sister, or the child or the spouse, it's just incredibly difficult to go through this role and try to help someone when they're struggling, and then I always joke that all my caregivers say well I'm gaining weight because I'm trying to feed this person all the time and then I'm the one gaining all the weight as the caregiver so guess what, you're going to have to exercise a little bit more or something because you're going to gain weight because you're trying to make the other person eat so much. But that's my advice to caregivers that you're going to have to watch your calories, because you're going to gain weight.
Dr. Roy Herbst: Chaitali, any thoughts on this?
Dr. Chaitali Nangia: I think Beth's line beautifully, I love that, I think I'm going to steal that line next time about the gaining eight, because I often get asked by caregivers on that line they feel so bad that they're loved one not eating or doing well, there's almost like a survival guilt or like why so, so it's a very challenging role to be in, but it's the magic glue we need that's the magic glue we need between the patients and the caregivers of the wonderful team of – I totally encourage that, I think they are essential in our delivery, effective delivery of care.
Dr. Roy Herbst: So where do people go to get information on services available that caregivers, is there a resource for this, Beth first?
Beth Sandy: Yes, and then I'll pass it to Isabella because she obviously has Facebook communities and things like that, one resource that I offer to my patients is a Facebook page called living with lung cancer, it's L-V-N-G with lung cancer, and it has a lot – I just actually presented a poster on this recently because I've been a part of it and done interviews for them, but they have like over 100 thousand patient members of this lung cancer specific community so there's a lot of great stuff on there, and patients with lung cancer are actually less likely to go to in-person support groups before COVID, before this was even a problem, going to in-person support groups, so the online community is really helpful here and now especially during COVID when we're not having these big group face-to-face meetings. So hopefully there's online – you have online access, and you have some familiarity especially in the Facebook section, because that's I think where a lot of these communities [00:42:00]. Then there's of course the American Cancer Society, there's Free to Breathe, the GO2 Foundation, these are some – some of them are more generalized. Free to Breathe is lung cancer specific but some of them are more generalized. But when you go to GO2 Foundation, you can click on an area for lung cancer specifically and then go into that community and get information and resources there as well as just support. Just talking to other people. It's not just for resources. Sometimes it's just to chat it up with people that are in your same situation. That can just be a comfort measure to talk to someone else who is going through something similar. But Isabella, I'd love to hear it right from you.
Dr. Roy Herbst: Yes, same.
Isabella de la Houssaye: So, just a few thoughts, even since I've been diagnosed the lung cancer patient community is evolving because people are actually staying alive. For the most part we're diagnosed late and until these TKSs and immunotherapy came along people died very quickly. So you weren't seeing a lot of people collecting in person or otherwise. But that's really changed, which is wonderful. The online communities that I do belong to, and someone asked in a question, so I'll be specific, the EGFR Resistors, there's also a Keytruda patient group and then for the drugs Tagrisso and osimertinib. These are all specific, private Facebook groups that you can use. Then in terms of a bigger organization like GO2 Foundation, you have longevity, offers resources. In our Philadelphia community you have a group like Ride Hard, Breathe easy, which is just a smaller group supporting lung cancer patients as well. So those are my thoughts on the connection – connecting.
Dr. Roy Herbst: Thanks Isabella. Chaitali, any thoughts on caregivers, resources, the importance of the whole care team? The care giver interacting with – tell us a little bit about the care teams, how you see it.
Dr. Chaitali Nangia: Yes, Like I said, I know we are covering now, that was my opening remarks. I think that's the magic glue like I keep saying. There's a lot of resources available. A bunch of them have been covered by both Isabella and Beth and I think todays are going to connect through all these social media platforms and there's many of them that our caregivers can access to. I'm always a big proponent for meeting for just in person as well and I – hopefully as we get more comfortable post-COVID we can resume that because I think that means a lot to patients and caregivers.
Dr. Roy Herbst: Great. We have a lot of questions in the chat. We're all seeing them. There are a couple of specific questions regarding people's care. I'll get to those at the end if we have time but really, I'll do the more general ones. [00:45:00] When you're seeking a second opinion, we heard that from the team, do you want someone who's specializing in thoracic oncology? What do you think Isabella?
Isabella de la Houssaye: Once I had my biomarker testing done and it was EGFR positive, I wanted to see someone who was specifically knowledgeable about EGFR. So it actually went to more than a thoracic oncologist. What I would say, yes you want a thoracic oncologist but you want one with a specialty in your area – type of lung cancer.
Dr. Roy Herbst: Right, what do you think Beth?
Beth Sandy: If you have lung cancer and you're seeing an oncologist and you want a second opinion, I would definitely seek out a thoracic medical oncologist. Someone who does just that type of disease because then you may get at least a different opinion. Even as I'm a – in a thoracic oncology practice, my patients will seek second opinions all the time and just go to another thoracic oncologist. It's great to go to a different institution completely because they will have different clinical trials and maybe just a fresh approach to it. But I would definitely seek a thoracic medical oncologist for sure if you have lung cancer.
Dr. Roy Herbst: Yes, I would say you want someone who specializes. Then you also want someone who really has knowledge of that specific problem. I often call one of my colleagues here at Yale if it's for small cell, for example, we have someone in the group who does more than the rest of us for EGFR mutation resistance and so forth. You also want an oncologist – he or she is going to call around and really try to use the network. There are so many nice networks now to try to find where the best ideas are and the best trials. Chaitali, you have – are you part of the City of Hope group there?
Dr. Chaitali Nangia: No. No, no but they're all in our connection of people that know City of Hope. But I think here's what I would say because I have a unique opportunity to be working in a cancer center, but I support a big community around us as well. So I think often times what I see is that patients may be coming to me from a very far away distance and they really are best treated by someone close to them, a community oncologist, that's easy to get in and out and not have to do a commute to come see me. I think from that standpoint I often get these second opinions that I would do and say, No I think you're fine. What your community oncologist told you is just fine. Check in with me or dial in with me here and there to see how things are going, clinical trial options and whatnot. So, I don't think it's completely wrong to be treated by your community oncologist who may not be a thoracic oncologist. But I would – I think for patients it would be – it should – I think it would be piece of mind to talk to a thoracic oncologist to make sure that everybody is on the same page. Also, you have that bridge for clinical trials and options should you need that. But if you're going to – if I'm going to offer you standard of care [00:48:00] because there's not a clinical trial you need at that time or applies to you, then why not get it in your own comfort with the community oncologist that's just next door?
Dr. Roy Herbst: Exactly. We have a few more questions. We have time for a few more. Here's one, what if you're about to start immunotherapy and then you discover you have a RET biomarker mutation? What do you do? Do you do the RET drug or do you do the immunotherapy or both? Beth?
Beth Sandy: Well, we have a saying at Penn, if it's not broken don't fix it kind of thing. So it really depends on what's happening. If you've started off with chemo and immunotherapy or immunotherapy alone and didn't necessarily wait for those biomarker results, you're in a little bit of a conundrum because what do you do now? Do you continue that and get a scan and if it's working, keep going? I think some of this depends on the biomarker. So we know that, especially with EGFR inhibitors, that using them in close proximity after immunotherapy, can give you significant toxicity, immunotherapy toxicity. So we avoid that with EGFR. It's not as well defined with the other targeted therapies, but I would be cautious. So this is one reason that we really try to wait to have all of those results back first. But once you're in that situation, because it happens, then you have to make a decision. Probably if you were responding to the immunotherapy, especially with RET, which is maybe not quite as strong of a driver as EGFR and ROS1 and ALK, I would probably continue on the treatment if it was working. Then know, in the back of my mind, that there's that biomarker that I would use in the future. I don't know, Dr. Nangia or Dr. Herbst, what would you guys do in that situation?
Dr. Chaitali Nangia: Yes, I think I agree. I often see this even with the KRAS, the new role of KRAS, that patients get KRAS tested, and it's come back and your patients are doing just fine on the therapy you were on, then you really don't – you're not going to stop halfway though and now switch. There are exceptions to rule, like we talked about, like Isabella mentioned, EGFR. You don't really want to do it. It's a false PD-1. You may create a bigger issue. So there are exceptions to the rule but by and large if you discover it halfway through treatment then it's better to finish the treatment you're on before you switch.
Dr. Roy Herbst: I would agree with that. We're in the final minutes here, anything the panelists want to bring up? You're all looking at the questions, anything you'd like to address? Yes, Isabella?
Isabella de la Houssaye: We haven't mentioned carcinoid tumors and I'm just wondering what the biomarker testing protocol is for carcinoid?
Dr. Roy Herbst: Well, I think you would probably test – it would be a non-squam, you would test the same way. Of course, it would be unlikely to have any of these mutations we're talking about. Carcinoid come in a whole series of degrees. They're neuroendocrine tumors. What do you do, Beth, at Penn?
Beth Sandy: So if this was a carcinoid that's a somatostatin receptor positive, we probably would not because your finding your somatostatin receptor. So, that's kind of your driving force. If you had a neuroendocrine tumor though that was more like a non-small cell carcinoid, I would – we test those. Though, to be honest, you're unlikely to find an actual biomarker in that. So, it kind of depends, like you said, on the degree of carcinoid and which biomarkers you would test for.
Dr. Roy Herbst: Agree. Well, we have a whole bunch of questions. People are putting their different thoughts regarding some of their treatment care. Brain metastases seem to be on everyone's mind. From a patient point of view, I didn't mean it that way, but Isabella, from a patient point of view, I would bet – I've heard this from many other patients advocates that work with us here at Yale and our [INAUDIBLE]. Thoughts about that and getting back on Tagrisso after immunotherapy if you can? You want to just comment?
Isabella de la Houssaye: I'm not sure what this [INAUDIBLE]. I can speak to brain metastases because I've had it. I've had brain radiation and it's – Tagrisso is a wonder drug and at the TKI in terms of working in the brain. It's unclear with a lot of the trials that are in my world whether these affect the brain and it's a bit of a scary place to go. But that's – I don't know. If someone has a specific question, I can try to address it.
Dr. Roy Herbst: Yes, someone is asking if they've been on immunotherapy and then they were off, can they go back on Tagrisso?
Isabella de la Houssaye: so just on the immunotherapy front, my one experience with immunotherapy front, my one experience with immunotherapy in the brain is with the CHILL trial, is that it actually really inflamed, with T-cell inflammation, the brain METS that creates a lot of problems that I don't think anybody expected. Which is why a lot of the immunotherapy trials don't take people with active brain metastasis I think, if that responds to the question.
Dr. Roy Herbst: Got it. OK, well we're just at the end of our hour. It's really been a pleasure discussing some – some have asked in the chat how they can come see any of us or our colleagues? Well, I would say, go online there are many cancer centers and practices around the country. I would look for teams that have expertise in thoracic cancers that practice in a multimodality manner. Meaning surgery, medical oncologist, radiation oncologist, nursing, APRN, social worker. Really, it's a team. I think most places would be very willing to talk to you on the phone, see you, offer clinical trials. I would agree, we want to constantly look for better ways to [00:51:00] deal with these cancers target resistance and we're making progress, but we have to continue to do even more. Would you agree Beth?
Beth Sandy: Yes, absolutely.
Dr. Roy Herbst: We're going to have a big meeting in the summer, The International Association for the Study of Lung Cancer is a whole society that's focused on this. I would also suggest their website as well. Chaitali, last comments before we break for the evening?
Dr. Chaitali Nangai: Yes, I think this was a great session. Thank you all for attending and also for a wonderful panelists and moderator. I think this is lung cancer awareness month. This was a great start. We have to start from platforms like this where we can engage with our patients and caregivers. I again would say that if you want to see it, start with what's close to you guys and then definitely try to see if there is a second opinion from a thoracic oncologist close to you. Then let them connect you with the networks to see which may be a best clinical trial fit for you and with the standard of care, get it done close to home.
Dr. Roy Herbst: Great. Isabella, the most thanks are to you as a patient sharing your experience with other patients. There's no greater deed and it's important. Because that's the way people are going to learn about what's available. So thank you for being here. You're actually a patient here at our center and I look forward to meeting you in person. But any final comments and we're really appreciative?
Isabella de la Houssaye: Thank you all for having me and I'm on – in the EGFR Resistors website. If anyone wants to reach out, I'm happy to respond to one-on-one comments. But thank you all so much. This was very informative for me as a patient.
Dr. Roy Herbst: Well, I'm going to turn it over now on behalf of CURE and it really has been an honor to be with all of you tonight. I've learned a lot. We could go on for hours. We'll do this again I promise. But everyone have a good night and I'll turn it back to the group from CURE. [00:52:55]