Bladder Cancer and Immunotherapy with Dr. Terence Friedlander at the 2020 CRI Virtual Immunotherapy Patient Summit

While immunotherapy for bladder cancer has a long history—the vaccine Bacillus Calmette-Guérin (BCG) was FDA-approved for treatment in 1990—new immunotherapies have significantly reduced the risk of recurrence for bladder cancer while also increasing the percentage of patients who see a complete response post-surgery. At the 2020 CRI Virtual Immunotherapy Patient Summit, we hosted a special breakout session on bladder cancer and immunotherapy to educate and empower patients, caregivers, and advocates.

Terence Friedlander, MD, chief of hematology-oncology at Zuckerberg San Francisco General and an associate professor of medicine at the UCSF Helen Diller Family Comprehensive Cancer Center, discussed what patients with bladder cancer need to know about immunotherapy and answered audience questions about clinical trials, COVID-19, and genetic testing, among other topics.

At the opening of the session, Dr. Friedlander provided an overview of the history of the development of immunotherapy for bladder cancer: the BCG vaccine, originally used to treat tuberculosis in 1970, was the first immunotherapy used to treat and even cure bladder cancer. He then focused on a rapid phase of discovery between 2016-2018, during which a number of checkpoint inhibitors were tested in clinical trials and approved for bladder cancer patients. Today, combinations of different immunotherapies or immunotherapy in combination with conventional treatments are showing great promise. Additionally, scientists are learning that giving immunotherapy after chemotherapy has, in some cases, been beneficial.

Dr. Friedlander then moved on to answer questions from the audience, including:

• Is there a way to predict which bladder cancer patients will have a better response to immunotherapies?
• Is PD-L1 a common mutation? What are some of the more common mutations in bladder cancer?
• If a patient suffers from autoimmune disease, specifically hypothyroidism and rheumatoid arthritis, is such patient a suitable candidate for immunotherapy?
• How long do you need to remain on immunotherapy?

Bladder Cancer and Immunotherapy Session Transcript

Tamron Hall: Welcome back if you're just joining us right now, it's my pleasure to welcome you to the Cancer Research Institute first ever virtual immunotherapy patient summit, and our breakout session on bladder cancer immunotherapy. I'm delighted to introduce to you Dr. Terence Friedlander, who is here to share the latest on bladder cancer immunotherapy, and answer your questions. Dr. Friedlander is chief of hematology oncology at Zuckerberg, San Francisco General, and an associate professor of medicine at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center. Brian Brewer from the cancer research Institute, we'll be sharing your questions with Dr Friedlander. So please be sure to put them in the Q and A box. Dr. Friedlander, thank you so much for sharing your expertise with us today.

Dr. Terence Friedlander:  Wonderful. Thank you, Tamron for that really lovely introduction and thanks to everyone for attending. It's really my pleasure to be here, to talk about bladder cancer and immunotherapy, which I think there's some really exciting developments. And so I think we should get to it. We'll talk a little bit about the history of bladder cancer, a little bit about the timeline of the development of these agents, and then we'll get to the Q and A session, which I know we already have a lot of questions coming. So bladder cancer, it's actually one of the oldest cancers to be treated with immune therapy. So if you go back to the 1970s, there was a vaccine called BCG or Bacille Calmette-Guerin. This was developed as a tuberculosis vaccine, actually almost 100 years ago.

And beginning of the 1970s, investigators used the vaccine actually inside the bladder for patients who had newly diagnosed non-muscle invasive bladder cancer. It's a bacterium. So giving this bacteria into the bladder, constant a lot of inflammation inside the bladder. Patients didn't like it very much, but it drove lots of different types of immune cells into the bladder. And the investigators found that the bladder cancer has actually gotten much better. In fact, some people were cured of bladder cancer because they got this bacteria placed into the bladder. And so that was really the first immune therapy and one of the first immune therapies ever used for cancer. What's pretty remarkable is that there's really never been a better drug to treat non-muscle invasive bladder cancer in the 40 years, since. There's some new studies and new trials now, but BCG really was sort of the kickoff for immune therapy and it shows that bladder cancer sensitive to this.

In the 1970s, 1980s, we developed other drugs like platinum-based chemotherapy, which was beneficial, but not a cure. And I think there was a lot more to work on here. There's a lot of room for improvement. So moving past 2016, that was really a major year for the community because the first systemic immune therapy ever to be approved was approved in bladder cancer. And that was a drug called atezolizmuab. So there was a study of about 200 patients. They showed that about 20 or 25% of patients who got this drug had really dramatic responses. Their metastatic disease, just got smaller in some cases disappeared. And their patients now who are alive because they got this drug now many years out, four or five, six years out from getting the drug. Since then we've had a number of other drugs become approved.

So in 2017, a drug called pembrolizumab was approved. That was a phase three study. That was actually one of the largest studies ever done in bladder cancer that was positive. And then three other drugs, nivolumab, avelumab, and durvalamab were also approved. But these all target the same pathway, which is this PD-1/PD-L1 pathway that I think you've heard a little bit about from Dr. George Asal. 2018, studies showed that giving the drugs, even before people have received chemotherapy for patients with metastatic disease, that there was activity that they were effective. And the FDA actually approved that for certain patients with bladder cancer who are not fit or not eligible to get Cisplatin, which was the major chemotherapy drug. So, we learned that you can give these drugs earlier. It was also active, if you get to give it to patients who are going for bladder surgery, have their bladder removed.

Beginning in 2019, and now up to today, there've been more development. So a newer drug called, Enfortumab vedotin, which isn't really an immune therapy, but sort of a new version of chemotherapy was shown to be very active when given together with pembrolizumab. So there's synergy between two different types of treatments. In 2020, we learned that pembrolizumab, one of these checkpoint inhibitors can be given early in bladder cancer. So for patients who have non-muscle invasive bladder cancer, whose disease has recurred, despite BCG, which I just talked about a minute ago, that some patients benefit from getting pembrolizumab and can be spared a cystectomy or a major surgery.

We learned sort of to are dismay that giving immune therapy with standard chemotherapy in a number of large studies, doesn't seem to be more beneficial than just giving chemotherapy first followed by immune therapy later. And we're still trying to understand why that is. Because in other diseases like lung cancer, when you combine these two drugs, you do get synergy. The other major study that was presented this year was a study of Avelumab, another PD-L1 inhibitor. That was shown that when it was given after chemotherapy immediately after chemotherapy, for patients who had good responses to chemo, that actually it was a very good benefit to giving the Avelumab in that context. And so that's become a standard option now.

Going forward, there are a number of clinical trials underway. It's what I'm really excited about, a different immune therapy. So ipilimulab, which is a CTLA-4 inhibitor combined with Nivolumab. We're waiting for data from that. Studies of a treatment called Pegylated IL-2 are in development, other types of drugs for bladder cancer, which really aren't immune therapy like antibody-drug conjugates, and Fibroblasts Growth Factor Receptor Inhibitors. These are non-immune therapy, but they're coming out, they've been approved. So, there's newer options for people with bladder cancer. So today these immune therapies PD-1/PD-L1 inhibitors are a major component of treatment for metastatic bladder cancer. Basically any patient who's eligible should probably receive these.

And then as I've mentioned already, there are a lot of novel agents under investigation. There's new types of viral therapies being given into the bladder to try and sort of replicate what BCG does. Giving immune therapy before or after surgery to remove the bladder, there's studies evaluating that. And obviously I've talked about some of these studies in metastatic disease. So there's really a broad development of these agents completely across the spectrum of bladder cancer. And that's really exciting. So with that, I think we're going to move on to some of the questions and I'm here with Brian Brewer. Who's going to, I think, take it from here.

Brian Brewer: Thanks a lot, Dr. Friedlander, and thank you for being here with us today. We're so excited to see you. Before we jump into the questions. I would just like to remind those of you who are watching today, that we do have a Q and A box. So if at any point you have a question for Dr. Friedlander, please go ahead and put it there. We'll try to get to as many of them as possible. Also, as a reminder, if you have not yet scheduled your confidential, one-on-one free clinical trial navigator consultation, you can do that at any time, and we'll be sharing that information with you again after today's summit. So thank you all for joining us, we look forward to your questions.

And with that, let's go ahead and jump in Dr. Friedlander. Clinical trials, as you mentioned, are such an important part of drug development, drug discovery, and approval. And one of the questions we're getting here is what's a clinical trial? I mean, that is a basic question we often get so we'd love to get your perspective on that. If you could explain that first, why don't we start there?

Dr. Terence Friedlander:  Sure. So a clinical trial is basically a study or a way of investigating a new agent or a new drug compared to a standard drug or a standard treatment. There are a lot of different types of clinical trials. So some clinical trials really just take a group of patients and give them all the same drug and just see how they do. Other clinical trials are comparative studies. So we take a new drug and an older drug, and maybe half the patients get the new drug, half the patients get the older drug. And that gives us probably a better level of evidence, a better understanding of which drug is more efficacious. So, that's sort of the basic outline of a clinical trial.

Brian Brewer: Efficacious, what does that mean? That why don't you?

Dr. Terence Friedlander:  Yes, that's a good point. So, which drug is better? Do people live longer if they get the new drug? Do people live longer if they

They got the old drug. Different trials may have different end points. So some studies may look at how long people live. Some studies may look at how much the tumor really shrinks down. Some studies may look at other end points in between that.

Brian Brewer: Okay, great. Thank you for that primer on clinical trials. So we have a question about that. If I'm part of a clinical trial study, and I have no idea that I'm getting the drug or not, how is that helpful to the study? Is it useful?

Dr. Terence Friedlander:  Sure. Yeah. And it's very useful. So, the best level clinical trials, the best evidence comes from taking a new drug and comparing it to maybe an older drug, sometimes just comparing it to a placebo, which is essentially water or a sugar pill. And many studies will purposely not tell the participants which drug they're getting because it can bias the study. If you know that you're not getting the active drug, the new drug, you might not show up to your visit. You might skip a scan, you might do something different, if you know ahead of time that you're getting the drug or not getting the drug. So to really know if a drug is working or not, we need to have these studies in which one group is getting it and one group's not.

And so even if you don't know which arm you're in, or you do know perhaps that you're getting the standard treatment, that's really crucial for understanding how the study works. Now, you may think, "Well, why should I take part if I'm not getting the new drug?" But this is really how we develop new agents. And really, any study that we propose we're really have to, we have to know at least that the new drug is efficacious, or we have to have some understanding that the new drug may be better. So at a minimum, everyone is getting the standard of care. One group might be getting something better, but that's really what the study is trying to understand and trying to test.

Brian Brewer: Great. Thank you for that. And for anyone else who has additional questions, some are still coming in, about clinical trials and whether or not they're right for them, I would encourage you to view our session on clinical trials presented by Dr. Ezra Cohen during day one of our virtual immunotherapy patient summit, which is available on the Cancer Research Institute website.

Okay. With that, we have a question coming in here. Is there a way to predict which bladder cancer patients will have a better response to immunotherapy and which won't?

Dr. Terence Friedlander:  Yeah. So this is a really good question and a really important one. We try and give the right therapy to the right patient. We don't want to give an ineffective or potentially harmful therapy to somebody, if we think they're not going to respond. And so we're constantly trying to understand this and trying to find markers that will predict a response. And so your question specifically is in bladder cancers, do we have markers that predict response to immunotherapy? The answer is yes, but they could be better. So, there are at least two markers that seem to indicate whether a patient's going to respond. One is a protein called PD-L1. And when tumors have a high level of PD-L1, that suggests that these drugs, which block PD-L1, are more likely to work. You can imagine if a tumor is no PD-L1 on it, and you give a drug that blocks PD-L1, well, it doesn't really matter because the cancer doesn't have PD-L1.

So there is, in bladder cancer, there is some studies that show that higher PD-L1 levels seem to correlate with better responses. The data is a little mixed, so it's not an absolute. It means that some people with low levels of PD-L1 still have responses, and some people with high levels don't, but on average, people with high levels are more likely to respond.

The other, the other group of patients, or I should say markers, that seem to predict response is actually doing genetic testing of the cancer. And I recommend that if someone has metastatic bladder cancer, almost all my patients get the tumor genetically sequenced. We look at the DNA. Tumors that are more mutated or have more errors or more problems in the DNA, tend to actually respond better to immunotherapy. And that may seem a little counterintuitive, but the thought is that every time there's an error or a damage or a mutation in the DNA, that creates something new inside the cell. And the immune system basically surveys our body all the time, looking for new things, looking for things that aren't self. The immune system can recognize us very well, but when it sees something new, it thinks it's a bacteria or virus and it goes and attacks it.

And so when cancers form, if they develop lots of new mutations, that can trigger the immune system to want to attack. And most of our immune therapies, in one way or another, are stimulating the immune system. So tumors that have a very high mutational load or high number of errors in the DNA seem to respond better. There's another sort of variant of that, which is called microsatellite instability, and that's a complex term, but the end result is microsatellite unstable tumors have high number of errors or mutations, and that's really what matters.

Brian Brewer: So thank you. We have a question coming in. Should I ask my doctor to do genetic tests, or will this be done automatically?

Dr. Terence Friedlander:  So, genetic testing is relatively new. It's only about five or six years that it's become standard practice for at least some cancers. So I recommend you talk with your doctor about it. The doctor has to order it. It's a special test. Many of them are covered by Medicare and private insurance, but you should really talk with your doctor to make sure. The question of also which samples to send, some people who have had multiple biopsies over time. In general, we usually try and send the recent tumor specimen. So, there was a cystectomy three years ago, but there's a biopsy from two months ago, probably should send that biopsy for the genetic testing, because that's probably more reflective of what's going on currently, rather than something from many years ago.

Brian Brewer: Okay. Another question coming in, is PD-L1 a common mutation? And if not, what are some of the more common mutations in bladder?

Dr. Terence Friedlander:  Yeah, so to be clear, PD-L1 is not actually a mutation. PD-L1 is a protein that sits on the surface of these cancer cells. And some cancers have a lot of PD-L1, some cancers have very little or none. So there's a big variations. Like I said, some have a lot, some have a little.

Mutations are changes in the DNA or errors in the DNA. And there are a number of mutations that are common in bladder cancer. Perhaps the most actionable today is one called FGFR, and I mentioned that in the beginning, because that stands for fibroblast growth factor receptor, and we have a drug that blocks that specific mutation. The drug is called Erdafitinib. It's FDA approved now, and there's about six other drugs, or maybe more, that are in development.

There are a number of other mutations that happen in genes. [inaudible 00:16:15] 1A, TP53 RB, a number of different… Becomes an alphabet soup. The challenge is most of those mutations, we don't yet know how to target. There's not a pill or an IV treatment that we can give that somehow then has activity. So really, the point of doing this genetic testing is to see if they're actionable mutations, meaning something that we have a pill for or a treatment for. And also, like I said earlier, to look at the total number of mutations because that might tell us that someone's more likely to respond to immunotherapy, or potentially less likely to respond.

Brian Brewer: Great. Question coming in about BCG. Why doesn't it work in more advanced stages of bladder cancer?

Dr. Terence Friedlander:  So BCG, like I mentioned earlier, is a bacteria that was developed initially as the tuberculosis vaccine. It was actually given worldwide, and if you grew up in India or you grew up in other countries, you may have received it as a trial. BCG, like I talked about in the beginning, was first given into the bladder, where it causes this dense inflammation. It really irritates the bladder, and drawing all those immune cells into the bladder gets immune cells to recognize the cancer. Truthfully, we don't completely understand how it works, even though it's 30 or 40 years old, but we know that lots of immune cells really get recruited to the bladder, and that's what helps.

The challenge with BCG is that it's a bacteria. And when you give it in the bladder, it sits in the bladder for a little while, and then we urinate or we pee it out. You can't get BCG intravenously because it makes people sick. We wouldn't really give anybody an intravenous bacteria because you can really actually get quite sick from it, if it gets into the bloodstream.

So, that's limited the development of BCG. We really can't use it in those other contexts.

But the reason we talk about it a lot, beyond the fact that it works in this one context where you're getting it into the bladder, it shows the idea that the immune system can get turned on and can attack bladder cancer, and that bladder cancer's immunogenic, meaning it induces an immune response. And that's really important.

Brian Brewer: Thanks. Another question from an audience member. Can a patient choose between chemotherapy and immunotherapy?

Dr. Terence Friedlander:  Yes, for sure. In fact, a large component, whenever I see a new patient, especially a patient with metastatic bladder cancer, is discussing the roles of chemotherapy and immune therapy. I'm obviously very excited, I think like most of my colleagues, about immune therapy, because we see these sometimes very dramatic responses, especially in patients where they may not have other really good therapeutic options.

That said, chemotherapy is effective. It is active. And I've had patients who have had, for example, a lot of bladder cancer, or they have cancer in areas that are causing them pain or interfering with normal organs, and chemotherapy can sometimes work very quickly and act fast and actually generate some durable responses. The problem with chemotherapy is that it's not a cure for bladder cancer, so no matter how much chemo we give to somebody with metastatic bladder cancer, we don't cure them.

So, the question really comes down to the timing, is, should we start with immunotherapy, and if that doesn't work, then give chemo? Or should we do the reverse? And it's sort of a nuanced discussion. And actually, as the trials have come in, what the studies have shown, at least as of today, is that if somebody is eligible, meaning they're sort of fit, their body can handle it to get Cisplatin chemotherapy, that is sort of the premiere chemotherapy drug, they should start with that drug. There's no study yet that has shown that giving something other than Cisplatin is better to start with.

That said, if somebody's not fit for Cisplatin, because it can be hard on the kidneys, it can cause hearing loss, it can cause numbness and tingling in the fingertips… So, if they maybe had hearing loss already, using a hearing aid, or they have bad kidneys, there are studies that show that starting with immune therapy may be better than starting with chemo. And that's one of the cases where we really use this PD-L1 marker. So, patients who have a high PD-L1 marker and can't get Cisplatin, they should start with immune therapy.

I do want to emphasize that this is really dynamic and this is changing almost year by year. So, even if you're taking really good notes, six months from now, the recommendation to start with chemo or immune therapy or some combination, that really might change as these clinical trial results keep coming in.

So, it's a really, I guess, exciting time to be doing this research because there's so much data in bladder cancer. For so long, there were just study after study that was just negative, negative, negative. And now we have positive studies. So, it's really dynamic.

Brian Brewer: Well, that's fantastic to hear and certainly cause for hope for those of us listening here today. We have a question coming in.

I'm a patient. I have an autoimmune disease, specifically rheumatoid arthritis. Am I a suitable candidate for immunotherapy?

Dr. Terence Friedlander:  That's a really challenging question. It's a really good one. It's really challenging to answer. So, almost all of the trials of immune therapy have excluded patients who have known autoimmune diseases. So, an autoimmune disease is a disease where our own natural immune system attacks our body. Rheumatoid arthritis generally attacks the joints, usually in the hands, the wrists, but can attack the joints all over the body.

And the concern is that by giving immune stimulants, you might make that rheumatoid arthritis get much worse. So, we don't have a lot of data about treating people who have autoimmune conditions. From some of the studies which have looked at this, suggest that about half of patients who have a pre-existing autoimmune disease, that disease will get worse if you treat them with one of these drugs. So, it's a very risky thing because if the condition is really serious, like Crohn's disease in the gut or ulcerative colitis, you can really make someone very, very sick. And even rheumatoid arthritis, you could really make the joints seize up and essentially incapacitate the patient.

But at the end of the day, it's always a discussion between the provider and the patient. And if the rheumatoid arthritis perhaps is very mild, maybe only requires taking some ibuprofen periodically, it might be reasonable to consider it. But again this is a very nuanced discussion and that's something I urge you to have with your physician. And if you see a rheumatologist, who's a doctor for autoimmune conditions, sometimes a conversation between all three, you and both doctors, is needed.

Brian Brewer: And what about on the other side of the spectrum? What if someone is immunocompromised or has HIV? Are they eligible for treatment with immunotherapy?

Dr. Terence Friedlander:  Yeah. Another great question, because these studies also excluded patients with HIV, patients with hepatitis, and some other immunodeficiencies. Fortunately, there've been studies now done, a couple specifically asking people who have HIV whether these drugs are safe. And it seems like they are, which is very reassuring.

So, here at San Francisco General, where I see a large number of patients, I have patients with HIV who we're giving these drugs to, and we haven't really seen any significant differences between them and patients who have sort of a normal immune system.

Some of the other immunodeficiencies, they're probably not as risky because we're stimulating the immune system. So, if the immune system doesn't work right to begin with, stimulating it probably is not as bad as if the immune system is already overactive and already attacking us. Stimulating patients who have those diseases might be much riskier. But still, there's not a lot of data here, so it's still an evolving field.

Brian Brewer: Multiple questions coming in on this one around bladder removal as part of treatment. And is immunotherapy helping patients with respect to not having to have their bladders removed?

Dr. Terence Friedlander:  Yeah. Another great question. So, as I mentioned at the outset, for patients who have non-muscle invasive bladder cancer… So, this means bladder cancer in the very inner most lining of the bladder that hasn't penetrated very deep into the muscle of the bladder. For those patients, immune therapy called Pembrolizumab is already approved if they're not responding to BCG. And we see about one in five people has a really nice response. I'm treating a number of patients with that treatment and we've avoided removing their bladder. And they're very happy, understandably.

For patients where the cancer invades into the muscle, it's still not so well-known. There've been two published studies of giving immune therapy to patients with muscle invasive bladder cancer, but almost all of them then had their bladders removed. That was the design of the study.

We have a study here at UCSF where we treated about 20 patients with a checkpoint inhibitor before bladder removal. And what we're seeing is, at least in the published studies, about a third to maybe a little more of those patients have no cancer present in the bladder. So, I think what we need are bigger studies to really confirm that response rate.

The challenge with using immune therapy and not removing the bladder for somebody whose cancer's confined to the bladder and is not metastatic… The challenge with that is removing the bladder cures people. It's a terribly invasive thing we do to patients. Removing their bladder changes their life completely, their quality of life, their self-image, but at the same time, it cures them of bladder cancer. And to say to patients, "We're going to give you an immune therapy but not remove your bladder," means that there might be some patients who develop metastatic disease because immune therapy doesn't work well.

So, it's a really contentious area, both sort of logistically but also ethically about whether we should be offering immune therapy and not taking the bladder out. And I would say for now, I don't recommend that because I think there are people who can be cured with having bladder surgery, having a cystectomy, who we're going to miss the cure on if we don't do it. That again may evolve, but it probably will take five or 10 years before we really have good, quality data about that. But an excellent question.

Brian Brewer: New question. Once on immunotherapy treatment with the positive response. What's the current thinking on stopping? I was an Opdivo and Yervoy for two years with good response. Treatment was stopped as standard of care.

Dr. Terence Friedlander:  Yeah. So that's also a really good question. I think that question was asked to Dr. George just a few minutes ago. We don't have great data about when to stop these drugs. So we know that about 20 or 30% of patients are going to have really excellent, durable responses. My longest response that I have from one patient's over five years now, patient had metastatic disease, got immunotherapy, and the cancer is essentially gone away, and it's been five years.

He stopped therapy about three years ago and has remained healthy, remained cancer-free as far as I can tell. There are reports of people stopping the therapy and then the cancer relapses. And so, the initial studies essentially gave immunotherapy indefinitely. They never stopped. And I think both the investigators, the drug companies and the patients that hold on, I'm not sure I can be on a therapy like this for the rest of my life, getting an IV treatment every two or three weeks, or maybe every four weeks for the rest of my life.

So a lot of studies have now said, we're going to give two years of therapy. If you're in a very good or complete response, meaning no cancer visible, or the cancer's really shrunk down to very little nodules or something like that, they're going to stop and follow. The current recommendation is to continue these therapies until we have better data, but that's really what the studies are going to try and tease out. I will say, like I said earlier, there are patients who have very good responses. And truthfully, when I think about this, the immune therapies are training our immune system to attack cancer. And our immune systems have memory. That's the reason you don't get the exact same cold twice, or you don't get the same infection, the exact same, one twice.

And so there is a thought that these immune therapies are helping to train our immune system to recognize cancer in the body, treat it, and then presumably remember it. And that's really the critical question is, does the immune system remember the cancer? So if one cell somehow managed to hide somewhere in the body and it starts growing a year from now, will the immune system just take it out before you ever know it. These are really important questions and we're hoping that we get more answers as studies roll out.

Brian Brewer: Thank you. We have a potential, I guess it's a side effect question. Can immunotherapy ignite the cancer rather than train the immune system to fight the cancer?

Dr. Terence Friedlander:  So I don't think that's ever been reported. Again, these are simulating the immune system, and generally when the immune system is active, that's a good treatment for cancer. So I would not be fearful of these therapies because they're going to make the cancer get worse. There are clearly side effects that I think we've heard about a little bit already today, but turning the cancer on or making it grow more, I don't think is a major concern.

Brian Brewer: Okay. Thanks. And we're almost out of time, but we've got to talk about COVID for a second.

Dr. Terence Friedlander:  Sure.

Brian Brewer: Are bladder cancer patients at all the more susceptible to COVID and those receiving immunotherapy, is it okay for them to get one of the vaccines that they're hearing so much about?

Dr. Terence Friedlander:  Yeah, so again, a lot's not known. It does seem that cancer patients may have a higher risk of getting sick with COVID so clearly avoiding it is important. It's not clear if it's the cancer that's making them more sick or is it just that cancer patients tend to be older, tend to have other illnesses as well, and so they're just in general a sicker population. So it's not so clear if the bladder cancer makes it high risk or just the general health. But obviously the best thing to do is to try and avoid it.

The vaccines, the two major vaccines that are rolling out, the Pfizer and the Moderna vaccine don't, at least theoretically, should not interact with bladder cancer. These are just very small, genetic snippets of the virus, and it's not really clear that that's going to make bladder cancer worse or immune therapy side effects worse. So I would actually recommend people get this because the risks of COVID seem quite high compared to the potential risk of the vaccine interacting with the immune therapy. At the end of the day, we don't really know, but I think that's probably the best advice we can get.

 Brian Brewer: All right. Well, on that note, that's all the time we have. Dr. Friedlander from the University of California, San Francisco. Thank you for joining us today. If we didn't get to any of your questions, Dr. Friedlander will be following up in a blog post on the Cancer Research Institute website. Dr. Friedlander, again, thank you so much for your time. Please stay safe, and we look forward to speaking to you sometime in the future.

Dr. Terence Friedlander:  Great. Thanks so much, Bryan, and to everyone out there, please stay safe as well.

Brian Brewer: Thank you.

Tamron Hall: Dr. Friedlander, thank you so much for sharing your expertise with us. And thank you all for joining us and participating in the Q&A.