Brain Cancer and Immunotherapy

Thursday
October 7, 2021, 4:30 pm -
5:00 pm
New and emerging treatments

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Watch On Demand

Session Description

Globally, approximately 300,000 men and women are diagnosed with a cancer of the brain and nervous system every year. Although significant advances have been made in understanding the biology of these cancers, the mortality rate has remained steady for more than 30 years. Immunotherapy offers potential new treatment options for this devastating set of diseases. Join Dr. David Reardon, director of Dana-Farber Cancer Institute’s Center for Neuro-Oncology, to discover new targeted therapies, immunomodulators, cancer vaccines, cell therapies, and oncolytic virus therapies currently approved or being explored in clinical trials. Don’t miss the opportunity to ask this leader in neuro-immunotherapeutics your questions.

 

Session Transcripts

Tamron Hall: Hello again, I’m thrilled now to introduce you to Dr. David Reardon, who is here to share with us the latest advances in brain cancer immunotherapy. Dr. Reardon is a professor of medicine at Harvard Medical School and currently serves as the director of the Dana- Farber Cancer Institute Center for Neuro Oncology. I’ll now turn it over to Dr. Reardon and Brian to get the most up to date information on immunotherapy for brain cancer.

Dr. David Reardon: Well, good afternoon, everybody, and I’d like to thank the Cancer Research Institute for putting together another phenomenal program this year for this patient summit, and certainly thank them for the opportunity to join you and to contribute to this particular session where we’re focusing on brain cancer. I helped to lead the brain cancer program at the Dana-Farber Cancer Institute in Boston, and our team, like many brain cancer teams around the country, work together utilizing oncologists, neurosurgeons, radiation oncologists and a variety of other specialists to help optimize outcomes for patients when cancer involves the brain, and there’s two main categories we think of for brain cancer. First of all, there are tumors that arise, originate, begin in the brain and grow within the brain. Those are called primary brain tumors, and then there are cancers that arise elsewhere in the body and lung cancer, skin cancer, breast cancer, and those cancers can subsequently metastasize from their side of origin to the brain, and we refer to those as metastatic or secondary cancers, metastatic cancers that spread to the brain that our team takes care of, or about 10 to 15 times more common than cancers that arise in the brain. We still see many, many patients with primary cancers that arise in the brain, but metastatic cancers are very common and frequent as well. These cancers, when they start to grow in the brain, whether they start there or spread to the brain can be very difficult to treat because they can have their involving an organ, which is so sensitive and important in our life, regulating our thinking and behavior and personality and function, and in order to safely treat them, we want to avoid damage, potential, potential harm or damage the treatment could cause to the normal structures of the brain and keep people as fully intact and functional as possible, and that can be tricky. Immunotherapy, I think, has great promise to be able to effectively get into the brain and selectively target the tumor and not damage the normal cells of the central nervous system or the brain, and therefore, as the potential to be much more effective to get to the target of the cancer in the brain and spare the normal brain tissue, but brain cancer is very difficult. One of the most challenging of all cancers to treat, particularly the tumors that arise in the brain primary tumors, and so far, those tumors in particular have not responded very well to immunotherapy, and we’ve learned a lot through research that these cancers are prototypical what we refer to as cold tumors, tumors where the immune system does not effectively integrate into the tumor to attack it. The cancers have a number of remarkable mechanisms that we’re beginning to unravel and understand that they utilize and exploit to protect themselves and ward off the immune system from recognizing the cancer and attacking it. These are called immunosuppressive factors, and this has been, I think, one of the main reasons why brain cancer has been challenging to treat from an immunotherapy perspective. But we’re learning a lot about these mechanisms of cancers and how they block the immune system, and more and more strategies are coming together to overcome these protective mechanisms that cancers are utilizing brain cancers are utilizing, and our hope is that immunotherapy is going to prove to be as effective for brain cancer, and hopefully, the not too distant future as it is has been for many cancers in the body to date.

This slide highlights many of the different strategies you’ve heard about at the conference of tapping into the potential of our body’s natural defenses, the immune system to attack cancer. We have checkpoint inhibitors that can dial up or dial down the immune response to help activate it into the tumor. We have cellular therapies like CAR T cells that are collected from the patient’s bloodstream, engineered in the laboratory, and then given back to the patient, usually like a simple transfusion that are then programmed to go and seek out and attack the cancer. We have vaccines very analogous to the flu shot. I hope everybody’s getting or will be getting soon as we approach flu season or like COVID vaccines. In this case, the cancer vaccines are designed specifically to help sensitize our immune system against targets within the cancer, and then there are a variety of other promising immunomodulatory agents that can help stimulate and engage the immune system to successfully attack the cancer. So these four main categories of immunotherapy treatments are being explored quite actively and from many different approaches for brain cancer patients, and I think some of the more promising strategies we’re looking at now are putting these agents together in potentially complementary combination approaches, where one approach can help make the other work more effectively and vice versa. It’s very important as we move forward in studying the effect of these treatments and improve improving outcome for patients to try to identify what we refer to as biomarkers that could be collected from the blood or other parts of the body. That help can help identify if a drug is working and which patients may be benefiting, and which patients may, if not be benefiting, identifying those subsets of patients, too. So biomarkers are critical part of these therapies to help us better understand how they’re working and which patients may be best able to benefit.

We just highlight what I referred to with the promise of immunotherapy for all cancers, but we’re hopeful in the in the field of brain cancer that we’ll be able to continue to evaluate strategies to tailor and individualize treatments specific to each patient that have the best chance of working on an individual patient by patient basis, and then, as I mentioned, to bring these treatments together and rationally designed combinations where they can enhance their activity and have an even better outcome than doing the treatments alone, and of course, continuing to work with our colleagues and collaborators around the world to take advantage of the research that’s being done, advancing our understanding of the immune system and how it can react for cancer therapy to develop even more effective and active approaches for brain cancer. So that’s just a quick overview to put things into perspective, and I believe we have a series of questions that have been posed and then a chance to take some live questions as well.

Brian Brewer: Indeed, thank you, Dr. Reardon, for that insightful review, and I also want to thank Dana-Farber Cancer Institute for lending your time to this program today, which is so important you raise so many important questions. I, the one that stuck out to me the most was thinking differently about tumors that arise within the brain tissue versus those that metastasize, and you’re seeing different response rates for immunotherapy with those two categories. Let’s go back into that. Let’s talk about what’s available right now. When you have a metastases versus what’s available now, if it’s a primary tumor.

Dr. David Reardon: So the tumors that spread to the brain of metastatic cancers, fortunately, we have seen success in many different types of cancer treatment for lung cancer and colon cancer and breast cancer and melanoma that are helping these patients live longer and longer, and when that happens, one of the possibilities that can evolve is that cancer cells can break off and spread typically through the bloodstream and make their way into the brain, and when they do that, they can have somewhat of a sanctuary there, because most of the treatments, chemotherapy, biologic treatments that we use to successfully treat cancer in the body do not effectively traffic and get into the brain. The brain has a separate protective mechanism called the blood brain barrier that prevents most of the cancer treatments we use for the body from effectively getting into the brain. So for metastatic cancers, the I think one of the things we’re appreciating is that as treatments have been more successful over time for many different types of cancers, this capability of cells to break off and move into the brain over time can emerge and lead to a metastasis or a spread into the central nervous system. When that happens, there are good therapies and, in some ways, some of the principles we use for the primary cancers of the brain surgery, trying to remove the tumor radiation to try to target and kill the cancer cells in a very targeted, localized manner, even some systemically administered therapies, a small percentage can get in and effectively treat the metastatic tumor. Immunotherapy has been remarkably successful for some types of brain metastases not all but for some types, and is continuing to be evaluated through much research, ongoing clinical trials and research as well. For these, for these tumors, for primary brain cancers, the ones that start in the brain and originate there. Those are the tumors that tend to be pretty refractory to immunotherapy treatments, at least when they’re administered as a single treatment by themselves, not in a combination, but a single. For example, PD one inhibitor or possibly a vaccine treatment by itself. These primary brain tumors have not responded. Historically, very well to these immunotherapy treatments, and we’re understanding. Why that is, and a lot of it has to do with strategies very sneaky and clever strategies the tumors actually use to wall themselves off and protect themselves from the immune systems, the immune system, cells identifying the cancer and being able to successfully attack it. So we are working very hard along with many of our colleagues to understand how tumors do that and then develop strategies to overcome that.

Brian Brewer: It sounds like a combination therapy is an approach. Right, because you said monotherapy might not those patients might not respond to a single agent, but perhaps there might be better chance of success with combination. That’s what I thought I heard.

Dr. David Reardon: No, I think, yes, that’s exactly right, Brian. I think we are a lot of us now have shifted the first generation of clinical trials where we looked at a lot of these therapies by themselves because by themselves, they were looking and have looked very remarkable for melanoma and lung cancer and kidney cancer, a variety of different cancers. These drugs by themselves have been able to have some remarkable activity. But when we’ve used the same strategy as a single agent in brain cancer, it hasn’t been enough and it has to do with, I think, these strategies, the cancers, many different layers of protection. The cancer is put in place to prevent the immune system from activating and successfully attacking it, even with one of these therapies trying to help and boost the immune system. So as we’re learning more about these protective mechanisms, we’re able to figure out how to put combinations together that can overcome those barriers, overcome those hurdles that tumors have put in the way, and in that in that way, give the immune system cells a chance to effectively attack the tumor and hopefully in the not too distant future, see the same types of success as we’ve seen in melanoma and lung cancer and kidney cancer, some of the other really promising cancers for immunotherapy.

Brian Brewer: That would be wonderful, but obviously it sounds like the brain is a lot more sensitive. You know, you don’t want to have an autoimmune response attacking the brain. So that explains why this is a lot more complex, perhaps, than with an organ other than the brain, thanks for explaining that, and it sounds like that is still an important scientific question that we’re pursuing at CRI and certainly Dana-Farber is as well. So another question from the audience, if you don’t mind, I know we’re almost out of time, but a question about age again, this is this comes up over and over again when we’re presenting these sorts of conferences. We understand now that the immune system might over time be less robust in its ability to respond to cancer or other threats. What are we finding out with brain cancer and immunotherapy in that regard?

Dr. David Reardon: You know, I think everybody was biased in that direction, thinking that as we get older, patients wouldn’t respond as well, and frankly, that has not been the case in general. Many of our older patients and primary brain cancer, for example, the most aggressive type that we deal with called glioblastoma, that is a cancer that increases in frequency as we get older. So the average patient in my clinic is in their 60s, 70s or older. But and certainly in metastatic cancers, we can see those in older patients, elderly patients as well, but for with immunotherapy treatments. In my experience, and I think the reports from others have shown that that initial thinking that younger patients are going to have the best outcome in older patients may not respond as well has not actually been realized and appreciated, and older patients seem to be benefiting as well. So these drugs, these approaches can enhance the immune system in elderly patients to successfully attack the tumor just like they can in younger patients. It’s not necessarily the intuitive expectation that younger folks will have a stronger immune system that hasn’t been the case.

Brian Brewer: We know a lot of these treatments are only available via clinical trials and clinical trials have a lot of exclusion criteria. Are you seeing this less and less of an issue? Age again, or is this still a criterion when deciding who can access a clinical trial?

Dr. David Reardon: Yeah, so that’s a great point, the clinical trials do have strict criteria for patients who can participate, and one of the strategies in defining those criteria are to lessen the likelihood of patients who are more at risk for side effects or complications. We don’t typically restrict by age in in brain cancer trials. We usually have trials for adults that start at 18 years of age, and then there may be parallel or companion trials in children, which would be less than 18. But we don’t typically set an upper limit. We do, however, have trial criteria that exclude patients who have significant heart, lung, liver, kidney problems because there are more at risk for side effects and complications. We do have criteria that exclude patients who have what we refer to as a poor performance status where they’re in in a significantly affected by the cancer or other conditions that their ability to function on a day to day basis and just take care of their daily needs. Independently bathing, feeding, taking their medicines. Those types of things for patients where their performance status is limited, particularly if patients are bedbound, for example, those patients are typically not allowed to participate because we worry they may be more at risk for side effects. But we don’t typically exclude for an upper limit on age. There may be a few trials that do that, but it’s not the norm by any means.

Brian Brewer: So it sounds like, you know, there are a lot of factors that go into deciding who can enroll in a trial or not, and an individual patient shouldn’t just rule themselves out. Sounds like ask. It sounds like the best advice. Ask about it where you’re being treated and say, you know, I think maybe I might be eligible for this. I’d like to find out if I’m not. How often do you find that patients have to keep asking, you know, you know what? What I’ve heard and talking with our patients is not always the first request to get into a trial is going to be bent with success. You might be turned down. What would you advise to patients who are considering trials?

Dr. David Reardon: I think you’re absolutely right that patients and families need to be their best, strongest advocate and reach out. Do a little homework. Try to find out what may be available through your local cancer center. Talk with your oncologist. They should also be one of your strongest advocates, of course, in helping to guide toward potential clinical trials that could be a good fit. But most cancer centers that have significant research programs, including clinical trials focusing on brain cancer, will have a contact either a telephone number or through the internet to be able to reach out and have what’s called an intake done or preliminary information about the patient. Just a thumbnail sketch would be taken to get a sense if they if there could be a good fit for a possible clinical trial to find out about. So a patient or family reaching out and contacting a center close by that has a known brain cancer program, for example, and going through that intake process with the goal of trying to identify if there may be maybe a possible clinical trial, I think that’s well worth doing. Your medical oncologist may be able to help with that, but a lot of times most of the patients who come to our Center for Clinical Trial Participation, it’s from their own initiative and reaching out on their own. They’ll call or email and reach our center, and that will their intake will come through and then be handled by one of our doctors or one of our research nurses to help provide information which we hope would be helpful to get them involved in participating in a good, well, fitting clinical trial.

Brian Brewer: Well, I hear loud and clear that, you know, patients as overwhelmed as they may be with this kind of news and their caregivers, the more you can advocate for yourself, the better, actually. I mean, the better access you might have to something that might work, and even we know like outcomes generally seem to be better for people who take an active role in, you know, getting the latest treatments going into those trials. So it’s very fascinating to hear you say that. I do have another question from one of our audience members specifically about cartoons out there.

Dr. David Reardon: One quick thing before we switch another question, but the other thing I want to emphasize is patients and families if they’re dealing with brain cancer, whether it be primary or metastatic. There are national organizations that have navigators. So if you are not sure about reaching out to your local center or even if you’re willing to travel to a more distant center, these organizations and I’m specifically referring to the National Brain Tumor Society, the American Brain Tumor Association and the brain tumor. Well, there’s a couple that are set up specifically for children as well, but the EBITA and the beats are two or national organizations that can help families with navigators available. I think twenty-four hours, but at least through working hours to help patients and families guide them toward centers that may have a clinical trial, that’s a good fit for them. So please keep that those resources in mind as well. They’re wonderful and very helpful.

Brian Brewer: Thanks. We’ll be sure to put those in the notes for people after the event. So if you subscribed or registered with your email address, we will follow up with you with some of those links from Dr. Reardon. I’ll also point out that the Cancer Research Institute provides a free service for one on one private consultations with a clinical trial navigator who can help you find an immunotherapy trial for which you may be eligible, and that information will also be shared by email to everyone. I think it’s wonderful that there are so many top-rated cancer research centers around the country who are providing this sort of, you know, treatment plans or options for patients. Amazing stuff, Dr. Reardon. All right. So with that, we’re going to go to another question from one of our viewers and that was around, you know, at what point should someone consider immunotherapy? I think there is a misconception that immunotherapy is it’s only something that’s available as a last resort or trials are a last resort. We did hear a lot about trials from Dr. Kunle Odunsi recently as part of this program, how these aren’t necessarily last resort options, but for brain cancer, like in your experience, when should someone begin having that conversation with their health care team?

Dr. David Reardon: As soon as possible, Brian, I think that conversation is critical and important to get off the ground as soon as possible. Immunotherapy treatments can help patients at different stages of the disease early in the middle and then late, but I think in general it’s reasonable to think that the earlier we can activate the immune system to help attack the tumor while the patient and their immune system are as strong as possible. That’s likely to have the biggest impact and provide the best likelihood of stopping the growth of the tumor, but also doing it in a durable way and maintaining that remission or preventing further growth of the tumor. So I’m a pretty strong proponent of having this conversation as early as possible and thinking of taking advantage of these particularly immunotherapy approaches as soon as possible. Many of the trials we’re doing now are integrating them into either surgery or radiation or even chemo approaches so that they can be part of that kind of integrated multidisciplinary approach against the tumor.

Brian Brewer: In speaking with your patients, how do they respond to this idea of the immune system and immunotherapy in general?

Dr. David Reardon: In general, patients and families are very excited about this, and they should be this is taking advantage of the normal natural defense system of the body and tapping into its potential to be able to overcome a harmful and potentially deadly disease and not relying on something that’s foreign, not physiologic and potentially harmful. Like unfortunately, all of the treatments we utilize chemotherapy radiation. Many biologic treatments unfortunately, can have side effects and may not be able to effectively discriminate the cancer cells from the normal cells in the body. So I think immunotherapy has great potential to be quite specific against the cancer. There are potential side effects, and we know we’ve learned a lot over the recent years about those potential side effects when the immune system’s normal balance is disturbed and it’s pushed to be more active than it normally would be, but nonetheless, in general, these approaches offer great promise in terms of being very specific against the cancer being very effective, having less effect against normal cells, being able to discriminate good from bad and because the immune system is uniquely designed to remember, it has memory our immune system once it’s sensitized a year later, five years, ten years later, has the potential to reactivate if it’s exposed to the target. If the tumor is trying to come back that that memory capability is really unique to this type of treatment that could help prevent recurrence and tumors from coming back. So there’s lots of different reasons. My patients and families are very excited about the possibility of being able to receive an immunotherapy treatment.

Brian Brewer: This is an important point that I’m glad you’ve demonstrated here that it’s a living drug, it’s, you know, the benefits of immunotherapy don’t stop after you’ve received treatment generally. You talk about memory and the fact that our immune system is capable of kind of keeping up with cancer sounds like the way you’ve described it. Cancer’s very, you know, nefarious, deceptive. It can it can prevent the immune system from attacking. But we also have these therapies now coming out of the science that help us to overcome those barriers. I think I’ve, you know, I would love your perspective on this immunotherapy, yet I wouldn’t say it’s a grand slam for brain cancer yet, and I would love to hear what you think is like, what are the next? What are the what are the positive things we’re seeing now and then? What are the next? What’s next?

Dr. David Reardon: So what I think many of the results, unfortunately for especially the primary cancers, some of the metastatic cancers, we’ve seen remarkable results with immunotherapy treatments, and I think it’s a fair generalization to say if therapies are working against the cancer in the body, they can be effective and work against the cancer in the brain. However, for the tumors that arise in the brain, those are the ones that are these really nefarious and tricky and clever ones that have a lot of mechanisms to protect themselves. They’ve already thought of this ahead of time and have these already in place so that when the immune system does try to mobilize, the tumor is able to either cloak itself and hide itself from the immune system or send out molecules and factors that actually turn the immune system off and deactivate it. So our research now is understanding those different mechanisms, and I think even though the preliminary round of trials haven’t been as exciting and promising as we’d like, we will be seeing better results. We will be getting better outcomes. Patients will be living longer. I have no doubt because of immunotherapy treatments, once we better understand these mechanisms and put the right drugs in to overcome and get around these factors the tumors are utilizing, we’re seeing immuno immune responses in the body. The drugs are able to activate the immune system. It’s a next important step to get those reactions in the body into the brain to successfully attack the cancer within the brain.

Brian Brewer: That’s a really positive message, and, you know, as I work at a Cancer Research Institute and I know that science is a long game and we’re learning more and more every single day thanks to the research that we’re able to fund with our donor support. Thanks to the work of people like you out there on the cutting edge treating, you know, a very difficult to treat cancer. So that’s wonderful. I’m going to I’m going to end here just to I want to talk about your pillow in the background. Never give up. I want to hear more about that. What does that mean and why does that inspire you?

Dr. David Reardon: Well, that’s actually a T-shirt. It’s draped over a chair, but it’s been in my office for over 20 years. Was given to me by a patient many, many years ago, and it’s it was a motto that he certainly had and maintained and shared with me, and I’ve kept it in my office ever since. So it’s just an inspirational comment that the patient shared with me a long time ago.

Brian Brewer: Well, thank you. Actually inspires me and I think everyone watching us. Everything we are doing, you and I together and CRI and Dana-Farber and all of the scientists and clinicians who are out there trying to advance immunotherapy. The goal is the same. We want to save more lives. So I just I’ll thank you right now for this. I think what you shared is super important. If we didn’t get to any questions for Dr. Reardon, he will be following up in a blog post at CRI website, cancerresearch.org. So if you have more questions about brain cancer, keep putting them in the Q&A. We’ll try to get to them as soon as we can. Dr. Reardon, thank you so much for your time.

Dr. David Reardon: My pleasure, Brian, and thanks to you and all our wonderful collaborators at Cancer Research Institute. We couldn’t do the work we’re doing without great support from organizations like yours. So thank you.

Speaker(s)

David Reardon, M.D.

Dana-Farber Cancer Institute

Dr. David Reardon is a professor of medicine at Harvard Medical School and currently serves as the director of Dana-Farber Cancer Institute’s Center for Neuro-Oncology. He previously served as the associate deputy director of the Duke University Medical Center’s Preston Robert Tisch Brain Tumor Center for 11 years. He is an active researcher with special interests in the design and implementation of clinical trials for individuals with brain and spinal tumors, focusing particularly on immunotherapeutics. He has also led investigations of molecular-targeting agents, anti-angiogenic reagents, cytotoxins, and other biologically-based therapies. Dr. Reardon has published over 290 peer-reviewed manuscripts. He has received the R. Wayne Rundles Award for Excellence in Cancer Research as well as the Award for Excellence in Adult Clinical Research by the Society for Neuro-Oncology in 2015 and 2016. He served as the tenth president of the Society for Neuro-Oncology from 2013-2015.

On-Demand Now Available

We are excited to announce that videos from our 2021 Cancer Research Institute (CRI) Virtual Immunotherapy Patient Summit are now available to view on demand.

The on-demand videos can be found on each session page from the agenda.