Educated Patient® Webinar: Individualized Treatment for Small Cell Lung Cancer

Ryan McDonald: Hello everyone and welcome to today’s live broadcast, a CURE Educated Patient webinar, Individualized Treatment for Small-Cell Lung Cancer. I am Ryan McDonald, the associate editor and director of CURE Magazine. We are pleased to bring you this webcast presented by CURE and in partnership with Genentech. There are just a few important announcements before we began. We encourage you to ask questions during the event which you can submit by typing them in the Q&A box you see on your screen. You will be receiving a survey via email tomorrow and as a thank you for watching the full webinar and completing the survey you will be entered to win one of three visa gift cards. And now I would like to introduce you to those who will be leading today’s discussion. We are pleased to be joined today by our moderator Dr. Jared Weiss, an associate professor of medicine in the division of oncology at UNC School of Medicine. Joining Dr. Weiss will be Tammy Allred, a thoracic oncology nurse navigator at the UNC Cancer Center as well as Jennifer King, the chief scientific officer at the GO2 Foundation for Lung Cancer and Randal Tietz, a caregiver of the patient with small-cell lung cancer. Thank you for joining us today and I will now pass things off to our moderator to begin the discussion.

Jared Weiss: Hi, good evening everyone. We have about an hour together to cover some of these advances in small-cell from various perspectives and I am grateful to have most of the perspectives relevant to patient care covered here. We’re going to interrupt each other a little bit, we’re going to have a nice conversation and I invite you to put your questions into the chat and we will happily address as many as we can if they are relevant to what we’re talking about I will try to integrate it and if not as we get to the end we’ll cover as many as we can. If I don’t cover something that is important to you feel free to drop an email after jared_weiss@net. unc. edu. I certainly don’t want to ignore anyone. With that I am going to start with a very exciting topic, the treatment options for small-cell lung cancer and their evolution. Tammy, you’ve been doing this just a little bit longer than I have. How has small cell traditionally looked?

Tammy Allred: Small cell has been almost like the underdog, it’s not got any attention that is actually needed, not the amount of research I feel that is needed over the years. Of course, it’s not as many as non-small cell lung cancer but still there are need. As I have told you in the past, that’s been my number one target is to get these patients more care, more treatment options, more quality of life, and a lengthy survival.

Jared Weiss: Randy, you’re the caregiver of a small cell patient. Would you share that feeling that small cell has been a bit of a desert that our treatment options are lacking?

Randal Tietz: Yes. From a patient or caregiver perspective, it is [00:03:00] a desert and we have a tendency to be dropped in the middle of it. Someone in the field knows basically where they are going even if it’s only in sand dunes but when you are a patient or a caregiver you don’t know the history and as you begin to make that journey the history becomes more interesting and possibly more informative. As I said before, we’re parachuted into this thing and it’s up to us to figure out which way to go and how to get there.

Jared Weiss: Thank you. And Jennifer, you’re an expert on the translational research side here. Tammy made a comment, I hope maybe we can flush out a little bit more that the progress in small cell has been slower than some other cancers such as for example the closely related non-small cell and certainly a lot slower than lymphomas and leukemias. I very much agree with that comment. What do you think are the drivers, why small cells have been slower to advance?

Jennifer King: I think there has been a lot of research. I don’t actually think it’s for lack of trying. There have been a lot of studies but it has been really hard to target in an appreciable way. There are very clear driver mutations in non-small cells that have been much more targetable as single gene mutations, which has brought new classes of drugs to non-small cell a little bit faster. That being said, I am very encouraged and feeling very hopeful that we are starting to see change in small cell. We do now have immunotherapies in small cell that are approved and in the clinic which is something we didn’t have a few years back and in addition there is – research is not ready for prime time yet but there are people really looking at different subsets of small cell and how we might be able to treat them differently. Some way the same as we are thinking about non-small cell as we move forward, so it’s really exciting for me to see that there is a lot of research coming and a lot of hope we have in this space.

Jared Weiss: Yes, I do agree with that. I think we are turning a corner in small cell with legitimate logical reasons for optimism at this point. Historically, I think biology that you hit on has been a problem. The complexity of small cell is a little harder than some other cancers. It tends to be driven by multiple backseat drivers, kind of like my car when I am driving my family more than single - sorry that funnier in my head - a single driver as primary biologic importance like some adenocarcinoma where you can drug it. We don’t have those immunotherapy and we had hope there would be more immunogenic than non-small cell. I don’t think that has been [00:06:00] proven true but historically our patients are sicker than many other cancers particularly non-small cell and that has been a barrier to trials. Trials require patients to be very healthy to get on, some of that is about patient protection if we are honest, some of that is sometimes about trial protection, probably a topic for another day but it is a barrier. Sometimes our patients are so sick they get their first cycle of chemo in the hospital because they have to and that can become a barrier to trial approval. The regimens are relatively easy to given the community, so community docs haven’t referred small cell as much as some other conditions. Our patients have been heavily stigmatized. We have actually published on that together in non-small cell I think [INAUDIBLE] small cell but I think that if you cared about people in this field for time you have seen the stigma is quite heavy in small cell because of the association with smoking because of the associations sometimes with lower socioeconomic status and it’s rare. It’s a less calming cancer. It’s 15% of lung cancer to non-small cells 85%, so I am endorsing none of these reasons but I think they are meagerly explanations of why history has been as it has been. But there has been a change. To my mind, the first meaningful change in a very long time came in the early 90s. In the early 90s, we had our first modern regimen CAV, which is a rough regimen. The A stands for Adriamycin otherwise known as the red devil. In my and Tammy’s neck of the woods, we have a little more fear of the blue devil but it’s rough is a gist of it. It’s so tough crowd. Thank you Tammy.

Tammy Allred: You’re welcome.

Jared Weiss: I am just going to assume everyone listening to us at home is laughing hysterically and I apologize about that. But when you’re thinking about the rough path we have been through, what our patients go through sometimes humor is the only thing to keep one sane. It’s a rough regimen but the one that does improve survival. In the early 90s, that was replaced with combination of platinum drugs and Etoposide. This improved the patient experience through decreased toxicity. It was more convenient for the patient. Unfortunately, actually it had no survival advantage. When topotecan came on the scene, CAV was the second line regimen and topotecan replaced CAV again without a survival improvement. A little less toxic, a little more convenient, maybe could argue if it was more effective but let’s say not a big difference was clear. We were really after the early 90s, we had no survival advantage until very-very recently and that’s [00:09:00] when the inspiration of the PD-L1 inhibitors came into play. Very famous study in our world that happens to be called IMpower133 randomized half the patients to the then standard of care platinum/Etoposide and the other half to get that same standard of care plus the addition of PD-L1 inhibitor atezolizumab. Before I talk about the results, maybe I’ll turn our attention to the scientist here, Jennifer to talk about what a PD-L1 inhibitor actually is.

Jennifer King: PD-L1 inhibitor from a patient friendly standpoint it’s what known as a checkpoint inhibitor, it’s a type of immunotherapy, which – the point is really to take the breaks off of your immune system that allows your immune system to then fight against the cancer. PD-L1 inhibitors are one main class of that that are now approved in both non-small cell and small cell. There are other checkpoints that there are drugs coming that we can see already in some small cell trials but the first big class was this PD-L1 inhibitors. I think Tecentriq or atezolizumab did show as well as there is more in this class that also [INAUDIBLE] is approved in this area as well now. Those who are really to me an important advance because we have seen from a patient perspective, patients have said that all this came to non-small cell first. That was where the survival advantage was shown first in metastatic not in small cell. So, even though I think it wasn’t the blockbuster that we wanted it to be in small cell, it was still exciting to see real differences in survival.

Jared Weiss: I agree. It was an interesting pattern. We measure drugs in many ways, two of them more common are metrical progression-free survival which is the time until either cancer grows or death from any cause or overall survival. The difference here interestingly enough was bigger in overall survival. We had improvement in immediate progression-free survival from 4.3 to 5.2 months, but overall survival of two months improvement, 10.3 to 12.3 months. While of course we would all like to be counting in years instead of months, I think what’s important here is that this came without much additional toxicity. There wasn’t a lot of human cost to this the way for example happens if you try to layer on more chemo drugs. Tammy, any thoughts on toxicity of these regimens, on triplets that are in common use.

Tammy Allred: I think using immunotherapy has actually given better [00:12:00] outcomes for our patients. They can tolerate the combination of drugs together. I am not a fan of old regimens at all because of I see what it does patients and their families when they are at home but as far as the triplets, as long as you educate patients and their families and encourage them to push fluids and small frequent meals, there is a way to get through this, but I think at the addition of immunotherapy has not added anything, if anything nothing is given improvement in the outcomes just by tolerating therapy.

Jared Weiss: Randy, anything to add or should I move on to the next event?

Randal Tietz: A couple of things, I will try to be brief. As someone who has done some reading after the fact, in other words, we were in up to our neck so to speak before I started doing a lot of reading on it. I found it as I’ll call myself a consumer, shocking that the platinum drugs were actually developed in the 1890s and from that time until we were involved in it and I parenthetically say my wife Carol has been pass the 10-year mark so we are historic anomalies but the combination of looking at drugs that are anywhere from 50 to 100 years old and there has been no improvement or no obvious improvement in being the red-headed step child of all the cancer research, it’s problematic and as our oncologist said at one point I hope that my children will look back on this and say wow that was really barbaric compared to what you’re doing now. I think that’s part of what we hope is that eventually soon something – how can I put it, something more will be there. That’s it.

Jared Weiss: Hopefully we can bury chemo. I think all of us who have been touched by patients have a healthy hatred of chemotherapy for its side effects and I think we’re stuck with sometimes using it because when we look at the global suffering of a patient there are two most dominant physical [00:15:00] determinants of quality of life in my patients that I perceive. Of course, there are other determinants of quality of life that are none of my business but in terms of the physical ones there is suffering bite from our chemo and suffering from the cancer. We have something that is not chemo that can relieve the suffering, we embrace it but when the back is against the wall, toxic as these agents are if they prevent more suffering from the cancer than they cause from their side effects, they can improve quality of life and there is actually some surprising data to that affect in small cell that drugs that I would not argue with you are barbaric improve quality of life compared to doing anything because of how barbaric the cancer is. But I spend two days of my week giving chemo and the other five trying real hard to bury it, so I wouldn’t disagree, these are barbaric agents.

Randal Tietz: Again if I may, in our journey through this I can’t say that the treatment was all that bad. I mean it’s obviously something you don’t want to do because you don’t want to ever encounter it, but it really when I say my doctor used the term barbaric, it was a relative thing. The system for administering the drugs and working on the mitigation of the side effects especially with oncology nurses and techs, it was wonderful. And the one thing that I would notice that I was frankly amazed by is I went to all of the treatment sessions with my wife and I never heard anyone say why me or poor me. As a group it was I look forward to going to the sessions because I was in a room full of people who are quite upbeat about their own situation and it was a surprise to me. It was a pleasant, a happy surprise.

Jared Weiss: I am going to go a little bit out of order or at least out of planned order here because we have gotten into the side effects of chemo. I think chemo has some classical side effects and to some extent they get more attention when we can actually do something about them. Nausea was classically the major side effect of cytotoxic chemotherapy. Before we got on here, Tammy and I were teasing each other [00:18:00] about our aging, I am old enough to remember chemo in the pre-4HT3 era and I know I just spoke a little Greek but [INAUDIBLE] when it was awful, people got [INAUDIBLE] needed them. And now we are in an era where with modern supportive care for anti-nausea drugs, steroids, the class of drugs called 5HT3 antagonist, any patient or caregiver would probably recognize Zofran, so the dominant one in that space and NKT antagonist, not NKT, what are they called – what’s fosaprepitant. Anyway fosaprepitant and Aprepitant, we have these new drugs and now you can eat a sandwich through chemo. With the same drugs as Randy has said the platinum is more than 100 years old, same platinum for the most part, very different side effect profile with anti-nausea drugs. The other classic side effects are blood count suppression and downstream sequelae of blood count suppression. If you dig into any of the major trials of lung cancer drugs and you look at the toxicity table, at the top of pretty much every one of our major trial blood counts and below them at some point you see things that are really at least in part consequent for them. You got three kinds – gosh my scientific collaborator would screech in horror, I hope I don’t make Jennifer screech in horror here in oversimplifying but for the most part you have three kinds of blood cells, white blood cells that help fight infection. In an ideal world, we will talk about this cancer. Red blood cells that carry oxygen to your tissues, when those go low that’s anemia, you might feel fatigued or have trouble breathing and platelets that help you clot. When these go low, we are at risk of infections, we have trouble breathing and we are real tired with the red cells dominating that but actually interestingly white cells and platelets when they go low also makes people feel tired. I think doctors took this for granted for a very long time. I’ll let Tammy speak to that because she has worked with a few – I’d essentially say generations of doctors or some generations of doctors but I feel like we took this for granted just as the cost of doing business because there was just nothing we could do about it for so long.

Tammy Allred: I can remember when a lot of patients the only treatment they would get was in the hospital because we didn’t know how to manage your side effects at home, how to prevent undue nausea, vomiting. It really just making have quality of life and then the drug started coming in and we were able to educate patients and families more to know how to keep – the way I tell patients now is your stomach is a pot of balloon water. Every time [00:21:00] starts boiling over [INAUDIBLE] food in it just [INAUDIBLE] that from bowling over, taking patients to prevent them from vomiting, instead of keeping the stomach empty and causing the vomiting to get worse. It's taken years for nurses, or at least myself, to kind of get that ingrained in my brain, but doing this is helping patients increase their awareness and decrease the amount of side effects. And that's the big thing. If we can take these side effects and give helpful hints to patients and families in advance, they're going to tolerate treatments much better, and maybe [CROSSTALK] give a schedule.

Jared Weiss: So, I wonder what everyone's experiences have been. But until very recently, the side effect of chemo that I felt the least equipped to help with as a doctor, that I felt I had the least tools to actually help my patients, has been fatigue. I have anti-nausea drugs, I have drugs to prevent renal failure, I even have anti-itching drugs. We have this whole armamentarium, but when people are tired, there are things that we do, if we're going to be honest, between four friends here and whosever listening, they didn't work that well. And so that that brings us to a next advance in small cell treatment that actually is not a survival advantage, but rather a supportive care drug, a drug aimed at improving the quality of life of small cell patients getting cytotoxic or traditional chemotherapy. And that is an agent known as trilaciclib, or for those who like brand names, Cosela, and it does something very interesting. Actually, to describe how it works, I want to first talk about how chemo works. So, chemo is poison. But it's poison with a very specific mechanism of action: kill cells while they're dividing. A cell has to be dividing to be affected by these poisons. That's why the cancer cells are preferentially killed by chemo, because they're dividing all the time to grow and cause their mischief, whereas the healthy cells in the body, for the most part, don't divide. But one of the exceptions to that rule are the cells in the bone marrow that make your new blood cells. The blood cells are constantly turning over, so these cells have to divide and they get poisoned by the chemo, which is why blood counts go up. So what trilaciclib does is it basically stops the bone marrow cells from dividing while the chemo is going by; it exploits a biologic difference between small cell lung cancer cells and these important bone marrow cells to hold the bone marrow cells out of what we call the cell cycle to stop them from dividing without doing so to the cancer cells, so that they're not poisoned by the chemo. And it was studied in three randomized phase two studies, and it was a pretty dramatic efficacy. So our top side effects are [00:24:00] graded from grade one to four. The primary endpoint was grade four neutropenia; with standard treatment, without this new supportive care drug, that was 53% of patients. In the pooled data between those three studies, that went down to 11%. The downstream sequelae, which is febrile neutropenia, or in plainer English, the combination of a fever with this low neutrophil count that makes us afraid of severe infections went from 9% to 3%. Supportive care needed for this, a drug called G-CSF that can help on the backend to deal with the side effect, but can cause brutal bone pain was halved from 56 to 28%. Same effects for anemia; 32% to 20%, as well as reduced need for transfusion and these drugs called ESAs that can be used to help, unless severe thrombocytopenia or low platelet count. And what I found remarkable about this was wasn't so much the numbers; the numbers were absolutely anticipated. And it wasn't so much the reduction in our traditional grading of side effects; it was designed to reduce side effects, it did that. What was really remarkable, at least to me, is- Randy, you called yourself a consumer earlier, I think of myself as a consumer too. I'm a consumer of data, I have to make these decisions together with my patients, or at least I have to decide what to recommend and what influenced me so heavily as a what I like to call a clinician consumer was that wasn't just about numbers. It translated to an improvement in patient-reported quality of life, and the choice of words is important to me in the evolution of how scientists and doctors look at whether drugs are working; not quality of life how I think about it, not quality of life how Tammy thinks about it, the quality of life from the report of the patients was improved, most importantly, for fatigue.

Jennifer King: Which is a tough one, I will add, because, to your point, fatigue, when you look at patient-reported quality of life versus clinician-reported quality of life, in study after study, patients report fatigue much, much, much higher than the clinicians report it in the same type of things. We have a lung cancer registry with patient-reported quality of life tools in it, and we consistently see fatigue across lung cancer, both types, all types, and across many treatments. And so it is definitely something that is problematic to patients, more so than I think is always recognized in the clinic. So definitely applies to you for recognizing how important that patient-reported quality of life is from someone who works in a patient organization.

Jared Weiss: Thanks. I think it's very important, of all of the advances we're going to talk about, in some ways, this is the most important one [00:27:00] for this audience to know about. Because I think, exactly as has been expressed, I think doctors under- gosh, I don't quote W very often, but miss-underestimate the side effects of our patients. I don't think that we really understand the patient experience in its entirety. And let me rephrase that to be a little more direct and harsh: we do not even vaguely understand the patient experience in its entirety. And, as a consequence, I think this is an advance that doctors underappreciate and perhaps are underusing. In order for the right thing to happen in the exam room, someone needs to know the right thing, and it doesn't always have to be the doctor. So I think this is an important advance for caregivers and patient advocates, as well, to know about. Tammy, I think you lifted your finger.

Tammy Allred: Also, a lot of times patients are reluctant to let the doctors know how severe the side effects are, because they're afraid they will stop the treatment, and that treatment is their only hope. Because a lot of times, patients will tell me something and then go in the room with you, and won't tell you half of what they've told me or vice versa. They'll go in, tell you something, and then tell me, I was afraid to tell the doctor that I've been puking every day and all this stuff, because I'm afraid he'll stop it. And I have to encourage them, and I try to do this on the initial visit. Always be honest and truthful, because we're not going to take it away. We're going to make it to where you can tolerate it, you can have a quality of life, because that's the main thing.

Jennifer King: I second that. That was very well said. I think patients do often, unfortunately, sort of hide some of those side effects to stay on treatment. It's particularly prevalent in clinical trials. They don't want to be taken off the trial, but it's true in regular everyday care, too, and we absolutely see that as well, that the side effects are downplayed, sometimes. So, to have advances like this, that can help side effects and quality of life are really, really important.

Randal Tietz: If I may speak to that point as well. Part of the idea of being fatigued or tired, when you're going through it, one of the principal things you have and you want to maintain is a good attitude and positivity about what's happening to you, and what you're doing, and what people are doing for you. And as a result, you don't want to admit, I'm too tired to do this, or I'm tired to the point where I almost dread doing something because you know you need to do it, and hope is on your side, and that kind of fatigue works to a degree against the hope. [00:30:00] So it's probably more common for people to say, yes, I'm fine, knowing they're not because to admit to themselves that things aren't right, that takes away a little bit of hope and you never want to give up any of that.

Jared Weiss: So, one final advance I want to cover is a new chemotherapy called lurbinectedin. Small cell lung cancer is a very transcriptionally active cancer, and it's a selective transcription inhibitor. Bringing it back to the plain English: it's a new drug for late-line treatments, second-line and beyond, so after carboplatin and etoposide and atezolizumab is no longer working. That seems to be a bit less toxic and a bit more effective than the prior standard of care, topotecan, although, in the interest of disclosure, they've never been properly compared head to head. It's comparing one trial to another, which we're not supposed to do, but we do all the time, and real-world experience. And interestingly, that agent is far more effective in patients whose cancer has previously been more sensitive to platinum-based therapy. In those populations, where, historically, we considered actually giving true drugs all over again, it had outcomes that can rival true drugs in that sub population. And what line it should be in is a controversial subject, but it is a new addition to our armamentarium that I haven't integrated into my practice. So, I want to shift gears a little bit to another theme. Actually, I'm sorry, before I do that, actually, Randy, if I can pick on you one more time. Actually, I think this is so important. Even though we're over time on this section, I'm going to stay here longer anyway. What do you feel your role is as a caregiver to a patient with small cell? And can you speak to the role a caregiver plays in working with their loved ones to determine which treatment option to go on their choices?

Randal Tietz: Which treatment? I'll reverse the order. Historically, for us, that wasn't an issue. We had etoposide and cisplatin, and there you are. And so the choice of what to do was pretty, well, limited by those factors. And probably the thing that I could bring to the table was consistency as being there for all of the treatments and being psychologically supportive. And, in my case, I enjoyed doing a lot of reading, [00:33:00] so I would read various publications that basically reinforce what we saw, what we knew, and what we were being told. And there's a certain degree of cheerleading involved in that. I would go on to what, at the time, was the Lung Cancer Alliance, and now I go to American Cancer Society, and National Institute of Health cancer sites, and they all said essentially the same thing: what your doctor is doing is working, so stay with it. And there was a degree of comfort in that, knowing that the professionals that we had placed the future in their hands were doing the right thing the right way. And if I could tell anybody, any support person, one of the more simple things to do is stay away from Dr. Google, and go find honest, sincere, scientific sites, which is kind of a problem now in our society. Science has taken such a beating lately that it's very off-putting to me. But at any rate, find these high-quality sites, go there, do the reading and realize that this stuff is dealt with on a daily basis, and they're doing exactly what they're supposed to do, and the nurses are telling you exactly what you need to do. They've handled the nausea, they've handle the sore throats, all of that. Just do it, stay with it, go through it, and it'll work. It may not be the best possible thing, but the only other option is not good.

Jared Weiss: I would call CancerGRACE.org as a resource that is vetted by expert thoracic oncologists. So that if you read something on there, it is going to be true. And I'll vouch for that personally, because I've put both a lot of my time and a lot of my donor dollars into it.

Jennifer King: And I'll say GO2 has a lot of education materials too. And we have a separate landing page at www. GO2foundation.org slash small cell now specific to resources for people diagnosed with small cell and their caregivers. So we also spend a lot of time with that. I also want to call out Randy's wife as a cheerleader in and of herself, because I know for a fact that she has participated in what we have, it's called a phone buddy program, but it's basically a peer-to-peer support program where you get matched up with people who've also been diagnosed, and she over the years and years and years, [00:36:00] has been a huge cheerleader to many other people who've been diagnosed, which I think can really also bring that hope, and I want to thank you and Carol for that.

Randal Tietz: It's a great program, and GO2 has a lot of easy-to-understand information. And it's a great place to start. And it's easily available. Actually, I ran into a website in England that actually rates their national websites. And if you go into that master page, it'll list the sites that they have tested and found to be legitimate. I don't know if such a thing exists here or not, but it would be good if medical professionals could list some of these sites, or in the adverse, say, stay the bleep away from this one, because it stinks. That's my two cents.

Jennifer King: And I would say that what you said is very consistent with what we see, and I'm going to guess Tammy is going to agree with me too, that we do see that a lot of caregivers are the ones doing that meeting, that research, really trying to support through finding the information while the person diagnosed is dealing with treatment.

Tammy Allred: And Randy, thank you, for the bottom my heart, for saying avoid Dr. Google. I preach that every day. Thank you.

Randal Tietz: I's such a wonderful, dangerous thing.

Tammy Allred: It is.

Jared Weiss: Jennifer, earlier on, you mentioned biomarkers. Biomarkers have been unambiguously a theme of our advance in non-small cell lung cancer; molecular markers, PDL-1. We are starting to get some biomarkers in small cell, and I think you mentioned this parenthetically earlier. Anything you might want to add to that of where you see hope here?

Jennifer King: I think in two different places. There are certain, specific targets that are being examined, things like DLL-3, which is one potential biomarker. There's been drugs that didn't work for that. But there's also new ways that may work to target that. So there's some things that sort of parallel what we're seeing in non-small cell that are at least being tried. And then there's some additional studies that are showing that with some more complicated assays behind it, you may be able to subset what small cell lung cancer looks like. So it may not be just one disease of small cell, it may have these different types, and different types might be more amenable to, say, be well treated with the immunotherapy or not. So it's still fairly early days, and I would say we're not ready [00:39:00] to make any sort of critical decisions on it, but it's really exciting to see that type of research coming down the line with hope that soon we may have a better idea who needs to take certain drugs and who they will not benefit to save the toxicity that we talked about. But then also do be able to have new types of therapies that might target a certain [INAUDIBLE]

Jared Weiss: I find this really exciting, too. You mentioned DLL-3. We just got data very recently on the efficacy of the newest drug targeting that, it's a cool new kind of drug. It's called a BiTE. And gosh, I'm not going to go into the science here, but it's really cool to those of us who do it; it basically makes a T-cell and a cancer cell get stuck together so the T-cell does its thing. And most importantly, it looked like it was working. So we saw a 20% response rate, but if you dig into the numbers a little bit, and you look at the patients who are at the highest dose that was safe, it looks like it's probably more like 30%, a very manageable side effects profile, some durability to it, a lot of n counting to how long patients have been on it. And that drug happens to be called tarlatamab, or AMG 757. In my opinion, it's on the list of things that I'm going to bet are going to be approved in the next few years and make legitimate advances. There are others, we're running low on time, but the [INAUDIBLE] is a newer chemotherapy that will probably be approved in the next few years for small cell that will probably help, and we had a bunch of questions about CAR T. CAR T is- gosh, how to say this in plain English? When you genetically change these T-cells that can attack cancer, you change what they attack to make them attack something that is on the tumor a lot. There was one being developed against the same target as tarlatamab, and that trial has been held for toxicity concerns. But stay tuned for a new product coming along against another target called GD-2. Should be a paper impressed within the next few weeks, and a trial hitting the FDA's doorstep for what's called IND on a roughly similar time period that I hope you'll hear more about eventually. So a lot of new classes; not just new drugs, but new classes trying to action these drugs, and a lot of new biomarkers. I want to shift gears dramatically. I wish we had not only another hour, but hours to talk about this because it's so important. Unfortunately, we don't, but I do want to at least mention it because it's so important; disparities in lung cancer. [00:42:00] Lung cancer has historically been stigmatized patients. And even within lung cancer, there's a tremendous literature on racial disparities in the treatment of lung cancer that is frankly rather disturbing. And one of the topics we were asked to talk about here was what to be done about this. None of us are experts in this area, to my knowledge. There are people who have PHDs in this, who study this for a living, but many of us live it and try to find it on a practical day-to-day basis. So minority patients are dramatically under recruit to trials. And I was asked to address what to do about that. And so I'm just going to wholesale steal from those who know more than me and share what the people who know what they're talking about have said works, and that we should be doing. So they say that we should be tracking this at a practice level, that you're supposed to start by looking at the percentage of each demographic group in your geographic area specifically. The percentage you see in your practice and then the percent you recruit at trials to define what problem you have on the most granular basis possible. Our literature shows us that at least in non-small cell, as we get more molecular testing in small cell, it'll come here, that part of the disparities in trial enrollment are driven by disparities in lack of molecular testing, that we're not testing our minority patients enough with these advanced testing methods. We need to actually offer trials to patients. We needed to assume that all races of patients have equal interest in trials and should have equal opportunity. There is a mistaken idea out there that certain races are less interested in trials. Again, this deserves days on its own, and I certainly don't want to acclaim any passions here, but that is a problem that providers have that attitude. And finally, we need to ask open ended questions of our patients about their attitude towards trials. Then we need to shut up and listen, which I'll confess as an MD provider, it's not that easy, especially when there's a lot you need to express in a disturbingly short period of time in modern healthcare. And then, you need to get over your own fear and stop tripping over yourself and give honest and direct answers about potential benefits. I think doctors are often shy about expressing the benefits of really high promised things. And we need to just - as my wife would say 'GTFO, get the -' over so important that we offer these options to patients, especially when they have such high promises they do in modern times. I'm intentionally pausing in case any of my co-panelists have more to say about this, if not, we can move into -

Jennifer King: Yeah, just a little bit. We are doing some work in this space across all types of lung cancer. And I think the barriers are at [00:45:00] many levels. And that's something that we need to think about, there are patient barriers around the education and we've worked some specifically in Alabama, and talking to patients who said, "No one ever told me why I was so important that I go on a trial, so that people like me were studied." Nobody's ever educated them at that level to say that the representation matters and we need to understand how treatments work across all races and ethnicities. And so there's patient education barriers, there's also lot of systemic barriers, and what trials get in, what centers and who can get to them, and changes which even able to be offered to a given patient. So it unfortunately is a very difficult problem across many levels. But one that we absolutely need to address, the FDA showed data at ASCO and big cancer meeting this summer that for the immunotherapy approvals, only about 2% of those patients were black, which means we really don't know for all the immunotherapy trials. So we really don't know how some of these drugs work in different patient populations, and it's critical. I think it's small cell, to a point you made earlier, it is even more important that we think about it, because we need these new advances. And unfortunately, the patient population does tend to be [INAUDIBLE] therapy it tends to be fairly dealing with side effects, dealing with these drugs, they have a lot going on and it's been even harder to accrue. And then there's performance status issues within the trials too. But I think it's something we all need to be aware of, and I always encourage patients and caregivers that I talk to, to ask your physician about clinical trials. "Should I be considering a clinical trial?" And ask if every major care of transition because it's important to have the conversation and understand why or why not, now might be a good time.

Tammy Allred: That's where it's important to me as part of being a navigator is go in and meet the patient initially and identify if there are issues with transportation, speak to the level that the patient can understand and try to address that. Start talking to the patient, "Now do you understand what I'm saying? Let's be open, I'm there to help you." And I also talk about clinical trials and as everybody knows with the Tuskegee Airmen - sorry, couldn't say that right, that really put a roadblock for clinical trials. So whenever I meet a patient, I'll let them know, this is strictly regulated and governed, and it's not something that we're just going to throw [00:48:00] it together in a basement and say, "Let's just try all the drugs together and see if it works. We don't do that, and we have to be open with you." And encourage patients that it's not like it was back in the 60's, this is what it is now. And you have to know everything and be part of and ask questions. And then with my patients also, look at their peer sources, because a lot of people are too proud to ask for help. So I automatically, I'll look at the patient's insurance or send them to find extra counselors, help obtain manufacturer assistants, obtain gas cards, when the weather starts getting bad, make sure that the patients have coverage so that their power bill won't be cut off. You just have to keep the questions coming. You got to ask the questions to the patients, to sometimes pull it out of them, and then ask their families. But that's the only way we're going to make this to where all patients get equal care and without any racial barriers included.

Jared Weiss: This is so important to make these trials available to our minority patients, right? There are so many reasons, I couldn't list them all, but the simple ethics of it is the first, right? As we get things that really work, we want to at least offer this as an opportunity to anyone who's interested and eligible. We want our trials to be valid and generalizable, right? No offense to middle aged white men, here I am, but trials can't be all about us, right? They need to cover everyone, they need to cover women, they need to cover black patients, Pacific Islanders, right? We need to know that our drugs work in everyone. This is particularly important because race can sometimes be a surrogate for different biologic tendencies in the cancer. So going way back in the day to an EGFR drugs were being developed, there are statistical differences between the races and the probability of having an EGFR mutation. So it's important that all races are studied in trials like that. And this extends to the science too, right? Most cell lines and models are derived from Caucasian patients, and that can be problematic. We need diversity all the way from the petri dish to real human beings in our trials, if we're going to make sure they're generalized to everyone. And if we're going to have equity in an era where trials really work, where they're not just about altruism for the person that comes after you, but also can extend duration of quality of life, sometimes dramatically if the person can goes on. So we have about 10 minutes left, I will confess we have not covered everything that I wanted to, that all of us wanted to, but I do want to make sure to cover what all of you cared about. And so I'm going to go into a lightning [00:51:00] round of questions. And try to, in rapid fire in eight minutes, get through all of you as if we can. First question is about CAR-T for lung cancer. So CAR-T, as I mentioned, is when you genetically reprogram the T-cell to attack what you wanted to attack. These are actually really hard in both small cell and non-small cell, because the overwhelming majority of the neo antigens in these cancers are private and not shared in plainer English. That means that all four of us that are speaking to you today were to get lung cancer at the same time, the foreign things on our cancer cells, that the T-cells can recognize would be mostly different between the four of us. And that makes it very hard to make a specific product if it's going to be very different between every patient. So there's other work that's a little more nimble and making individualized products for individualized patients. Another kind of cellular therapeutic called TILs or Tumor-infiltrating Lymphocytes, I don't have time to go into the details of that, but are made actually from the T-cells in a patient's own body and can affect, address that heterogeneity and personalized vaccinations is becoming a thing that can address that. But if small cell and non-small cell are somewhat kind of conserved targets, DLL3 and GD2 are probably top on that list for small cell. So non-small cell question, how long on average will a targeted therapy work? It's supremely different from patient to patient. But with modern targeted therapies, we look for at least 20 months on our statistical measures, but the real benefit is sometimes quite a bit longer than that, because there's strategies to prolong it. There's a question about transformation to small cell and hope for there. There is hope there, that's a relatively rare mechanism of resistance, typically of EGFR mutated lung cancer. But very often, when you give it small cell chemo, you can knock down harder, you can totally eradicate the small cell component and go right back to the EGFR playbooks onto those patients too very well. And I'm assuming someone's asking about a particular patient, I hope that ends up being true for them. Someone shared that your wife is a 10-year survivor of stage IV and said that her husband's had - he's her husband, had EFR non-small cell lung cancer for two and a half years. 33 years old, wow. I have younger patients, I'm sorry, that's an injustice of the universe. I don't know why bad things happen to good people. But I'm going to move on, so I don't start crying on a webinar. Neulasta. Neulasta is a drug that can bring up blood counts after chemo is given. It's a shot given a day after. It does help but it only helps with neutrophils, and it can cause a lot of bone pain. So it is a help but it's a problematic help. So question about brand names and generic names. [00:54:00] Carboplatin. Is carboplatin or Paraplatin, if you're way the heck back in the day. Etoposide, it's pretty much always called etoposide. Same with topotecan. Lurbinectedin, anyone know what lurbinectedin's brand name is? I actually don't remember.

Jennifer King: Zepzelca.

Jared Weiss: Zepzelca. Thank you, that's a good name.

Jennifer King: Zepzelca.

Jared Weiss: Trilaciclib is Cosela. Tarlatamab does not yet have a brand name, its other name is AMG757, I realized that's moving in the other direction. Any others that we mentioned that I'm missing here for giving the two names? This next one, I'm actually going to slow it down on, because this is actually pretty important. Someone commented, Randy, about attending appointments with your wife and the importance of it. And commented that in the Covid era, patients are going to their appointments alone. I don't care if we use our last four minutes all on this, it's so important. Anything to say about that?

Tammy Allred: I did. You've got to be an advocate for yourself and your family members. Talk to the provider, talk to the nurse, talk to the office manager, whatever it takes. You need to be there. If nothing else, then by remote, by phone, do FaceTime with the patient. In that way, you can hear what the provider's telling the patient. The patient does not need to be there alone. They can't intake all this by themselves. So FaceTime, video chat, while they're in there, or go and say, "I've got my vaccine, I'm wearing my mask, I'm coming in there because I need to know. And my family needs my - or I need my family support with me." There's no reason that this should be the situation. This is vital. I'm getting off my soapbox.

Jared Weiss: The other thing I would add to that beyond underscoring just how useful video chat can be. And for those who are technologically adept, your doctor or if your doctor's as old as me, his fellow or nurse, will know how to do this, can help you with it. But the other thing is masks really work. So my hospital has a ridiculously strict mask policy. Security will escort you out if that mask is under your nose. But in - what are we in, about a year and a half of Covid, our rate of in hospital transmission remains zero. We're not the only hospital that can make that break, pretty much every hospital that's implemented those kind of strict precautions, and we didn't know that at the beginning. In defense of the people in fancy suits who didn't let patient's caregivers come with them, they didn't know that and they were looking to not have dead caregivers or more dead patients. We didn't know everything at the beginning. But now, a year and a half later, whenever you feel that, that we know that now that these precautions can work, there's no reason that a cancer patient should be going through treatment alone now, knowing what we know now. So you got off your soapbox, I got right off mine.

Randall Tietz: If you've got a room for one more edge [00:57:00] of a soapbox, again, if someone is going through this, my single biggest suggestion, the most important one is get help. Stand up there.

Tammy Allred: Exactly.

Randal Tietz: And get help. Get help from the nurses. Ask the doctors. Some doctors are not good at communicating, so ask again or ask the third time. Do what you need to do. We joined a support group after treatment was finished. In our area, it's one of guilder's clubs, long story there. But it was tremendously helpful. They had presentations by doctors and sometimes, you could go and ask the question that you forgot to ask before. It's wonderful. There used to be a commercial here, you should be an informed consumer. You need to be an informed patient, you need to be an informed caregiver and you have to advocate for yourself. In our case, there was very little advocacy necessary, our people were just, they were golden. Doctors, medical text, oncology, nurses, they were wonderful people. But if they weren't, you have to stand up for yourself. And my wife does this with her phone buddies. If they don't get an answer, she'll tell them frankly, "Go back and get that answer. You have to know. You have to be involved in this." There's too many patients that are just floating along, hoping for the best, and it's not enough. Hope is wonderful, you need it, but you have to be informed and you have to be an advocate for yourself. I'm done.

Tammy Allred: Exactly.

Jared Weiss: So we're running out of time and I'd like to give the panelists an opportunity for final thoughts. I was going to start with you, Randy, but I'm going to give you a moment to let your voice recover since you've just been speaking and go to Jennifer for your final thoughts, closing thoughts.

Jennifer King: And I kind of want to second Randy. I feel like you have to advocate for yourself, you have to become educated using caregivers. And caregivers doesn't have to be a spouse, it can be a friend, it can be anyone in your circle, to help educate and inform and discuss the right treatments. And as we discussed earlier, the right treatment, perhaps, for your side effects. Be honest, learn which you can and talk to everyone and communicate. I think advocating for yourself is so important. Go2foundation it's here for all of those in the small cell communities, as I mentioned, we have a landing page, go2foundation.org/smallcell [01:00:00] or a helpline 1-800-290-2436, and you can call and talk to someone about things that you need. But we really are excited, the other theme I want to leave with is hope that we are seeing these new advances, we can have these webinars talking about the new things coming, the new things that are already on the market, and that we are expecting in the next couple of years, and that's a very exciting thing moving forward.

Jared Weiss: Thank you, Jennifer, and thank you to everyone at Go2 for everything that you do for patients, it's wonderful to have to that resource. It takes a village to support a patient, and thank you for being such an important part of that village. On that same theme of important parts of the village, Tammy, any closing thoughts?

Tammy Allred: Yeah, as I've talked to Jared before. Sorry, again, I'm tired of seeing my patients suffer, so I'm glad that we finally got help for small cell. I've lost a lot of close patients, and it shouldn't be that way. Be an advocate, be a self-advocate, fight for what you need and fight for your family. Sorry. I get very passionate about this. And then when you go to the doctor, if it's your first visit or your 100th visit, if you don't understand, don't let him leave or don't let the nurse leave, keep asking questions. Ask for assistance, ask for anything. But we're going to give you hope no matter what. Sorry.

Jared Weiss: Tammy, thank you for everything you do, not just here, but in the clinic and with patients everyday. I'm a witness to all the human suffering that you've personally reduced then. I'm not as prone into tears, but thank you. Randy, closing thoughts.

Randal Tietz: So I want to thank you, Dr. Weiss, as a representative of the entire oncology community research and clinician. And to Tammy, it's obvious that you - both of you - care. And as representatives for the community, that care is important and I congratulate you both on first doing your job and second coming back to work the next day, because that's always the hard part. They talk about running into a burning building, you can do that, but it's that when you have to come to work tomorrow, and deal with the things that work and the things that didn't. And those things that didn't are terrible [01:03:00] sometimes. Thank you for coming back. Thank you, Doctor, for putting yourself out here and talking about the specialty of your area. And again, Tammy, as a representative of hundreds of thousands of oncology, nurses and specialists, thank you and thank you to all of them.

Jared Weiss: Wow. It's rare I'm at a loss for words, as Tammy, I could tell you, but I feel like I am. Thank you to all three of you, thank you to everyone's who asked three questions, thank you to everyone who's gone on a trial, thank you to everyone who's cared for a patient. It really takes a massive amount of, a 360 of resources to maximally support a lung cancer patient, to reduce suffering and extend life. And we're all a small part of that. There's a lot that we've talked about today. Most very recent advances to the standard of care that are improving quality of life, improving duration of life, finally having some of those that are actually in specifically, a quality of life, which from a philosophical perspective, that's probably the wrong choice of word, but it's a breath of fresh air, to have that attention. There's a lot more to come. We really scratched the surface today, there's a lot we haven't talked about. I'm sorry to those who organized it, if it was important and we missed. I'm sorry for everyone listening if we didn't cover something important to you. There can always be more webinars. We only had an hour together here today. And feel free to contact any of us if we can help further with anything specific. On that note as well, if you missed anything on this webinar that you want to go back to, it will be available on the webinars on demand page of curetoday.com, within just a few days. So thank you to the panelists, thank you to the audience for attending and participating. Thank you to CURE and for our partner Genentech, for making today's webcast, possible. Don't forget to check your email tomorrow for the survey to be entered to win a gift card. And thank you everyone for joining, we'll see you next time.