As the second most common male cancer in the world, roughly 1.3 million people receive a prostate cancer diagnosis each year. In its early stages, prostate cancer is highly treatable, but when advanced, effective treatments are limited. That’s where cancer immunotherapy offers new hope. There are already two FDA-approved immunotherapies—a therapeutic cancer vaccine and a checkpoint inhibitor—and many more promising treatments in clinical trials. Join Dr. Ana Aparicio of the University of Texas MD Anderson Cancer Center to discuss exciting scientific and clinical research. She’ll answer your questions about biomarkers and genomic sequencing, combination therapies, clinical trials, side effects, and more.
Tamron Hall: Welcome back, if you’re just joining us, welcome to the 2021 Cancer Research Institute Virtual Immunotherapy Patient Summit. You’re in the right place to get the latest information about the cutting edge of cancer treatment. It’s time now to turn to prostate cancer, a disease that is diagnosed in more than one point three million men each year worldwide. Immunotherapy offers some promising new treatment alternatives, and here to tell us about them is Dr. Ana Aparicio. Dr. Aparicio joins us from the University of Texas MD Anderson Cancer Center, where she is an associate professor in the Department of Genitourinary Medical Oncology. There, she specializes in the treatment of advanced prostate cancer. Brian Brewer from the Cancer Research Institute will be sharing your questions with Dr. Aparicio. Dr. Aparicio, thank you for sharing your expertise with us today.
Dr. Ana Aparicio: Thank you very much for the introduction. I am a medical oncologist at MD Anderson, and I specialize in treating prostate cancer in clinical trials. So thank you for the invitation and thank you to CRI for organizing this very important event so that we can really spread the information with regards to the importance of clinical trials.
So why don’t we go ahead and get started? You can see my first slide. I just wanted to sort of talk a little bit about how we’ve really witnessed a revolution in the last few years. For many years and decades, all of our cancer research really focused on the cancer cell itself to treat cancer, but we realize that there’s obviously a lot more in a tumor than just the cancer cells, believe it or not. There’s a whole structure that supports those cancer cells and allows those cancer cells to grow or actually prevent them from growing, and so that’s where immunotherapy has had such a profound effect because first and foremost, of course, has been the immune cells and their ability to either curtail the growth of the cancer or promote, in some cases, the growth of the cancer.
We’ve come to realize that in this very complex tumor microenvironment and this very complex immune system, there are some cells that will make the cancers grow and there are some cells that will help kill the cancer, and so we’ve really learned a lot over the last few years about the function of these cells in a particular microenvironment, but also what drugs and what treatments we can use to harness the immune system to help us treat the cancer.
This obviously has all been done through clinical trials. It’s been a new type of treatment for cancer, and with that comes not only the excitement of the more effective treatments, but also the learning curve of how we use these drugs best and there’s been some learning curve with regards to what side effects these drugs might have had when we first started using immunotherapies. I remember designing a clinical trial in prostate cancer, and some people were very much against it because they felt the toxicity was going to be excessive, but the truth is that it’s not that excessive. It’s not different from chemotherapy toxicity in the sense that we can learn how to manage it, and now, 30 years ago, people would get treated with chemotherapy, had to be admitted to the hospital, and now people come in to see me in the clinic in the morning and then get their chemotherapy, go home and don’t come and see me again until three weeks later. We’ve come a long way, and so all of that learning and all of that understanding of how to best manage the side effects that might be associated with some of these treatments has to obviously be done on clinical trials. So I really think that clinical trials really should be thought of as a partnership to develop the effective cancer therapy. We can’t make any advances in the absence of well-designed, scientifically-rigorous clinical trials, and these clinical trials obviously are going to look at new treatments, new immunotherapies, but also combinations of some of the existing immunotherapies between them with some of our traditional treatments like chemotherapy, radiation or surgery.
I think that that’s the that’s the key message that I had wanted to start off with that, there’s a lot of excitement with regards to immunotherapy. It’s clearly a new modality of treatment for cancer care. It has huge potential. There’s a lot that has yet to be tapped into, and we need to expand our knowledge and our understanding through clinical trials so that we can make cancer a thing of the past. With that, I we can, I guess, move on to the questions.
Brian Brewer: Dr. Aparicio, thank you so much for that brief overview around the exciting advances in immunotherapy for prostate cancer. One of the most prevalent forms of cancer to affect people around the world and especially in the U.S. So of course, any advances that we have in immunotherapy certainly welcome, any new hope, so thank you for sharing that. I’m going to jump in right now with some questions that we’ve received from audience members as they were registering. So they’ve submitted these questions in advance. Those of you who are watching live and who have not yet submitted a question, feel free to take advantage of that Q&A box right on the right side of your screen and we will be looking at those, and hopefully we’ll be able to get to all questions in the short amount of time that we have allocated for this session. Any questions that we don’t get to, we will follow up on a blog post at the cancerresearch.org website and you will be getting an email about that. So with that said, let’s just go ahead and jump right in. Dr. Aparicio, a question from one of our attendees, “Is immunotherapy effective on prostate cancer when it’s metastasized? So are things different when something has metastasized versus when it’s local?”
Dr. Ana Aparicio: Yes, very much so, actually, one of the first immunotherapies that was FDA-approved was, in fact in prostate cancer, and in fact it was in the setting of metastatic prostate cancer, and that is super useful T. So, in our clinical trials with the immune checkpoint therapies, some of the treatments that have been approved in melanoma, lung cancer, et cetera, we consistently see in our clinical trials a subset of men with metastatic disease that have very dramatic and profound and durable responses to the to the immunotherapy. So the answer is yes, absolutely. å
Brian Brewer: Another question from one of our audience members. Similarly, “Are we again talking about more advanced stages of disease and whether we’ve seen some indication that immunotherapy might be more effective at those more advanced stages versus earlier stages and metastasis again?” So I think you already answered this, but is there a difference between early stage prostate cancer and late stage prostate cancer, and whether or not a patient might be eligible for immunotherapy?
Dr. Ana Aparicio: Yes, so the early and the late in prostate cancer have two different meanings. One is early, as in, localized, it hasn’t spread outside of the prostate, versus late, as in, it’s already spread outside of the prostate. Within the ones that are already spread outside of the prostate is early in the treatment course of that disease or late in the treatment course of that disease in the sense that have we gone through hormone treatments or most of the treatments that are available for metastatic prostate cancer? So because the majority of people that have localized prostate cancer actually do well despite of this, and a vast majority of prostate cancers, probably the localized setting don’t need treatment, which is not to say that some don’t. So you have to go check it, you do have to give it some thought, but I think that currently the effort in regards to the immunotherapy development has more is more focused on the advanced disease and the metastatic disease. Within the metastatic disease, there is a spectrum of clinical trials looking at different stages of the disease. So, for example, the immunotherapy that I mentioned earlier is one that’s actually probably more effective in the earlier stages of that metastatic disease.
Brian Brewer: So it sounds like there are a lot of different treatment approaches based on an individual patient’s course of disease, time of diagnosis. Sounds like there are actually a lot of options available. At what point should someone say, “Doctor, what about immunotherapy?”
Dr. Ana Aparicio: So I believe very firmly that when available, a clinical trial should always be the first choice because I think that we can and should do better than what we’re doing. So at any stage of the disease, if a clinical trial is available, I think it is very reasonable to consider participation in it. I have to say, clinical trials are vetted by everybody and their mother, and when I say everybody, I mean it. I can come up with any idea and there will be a hundred people that, I’ll have to write it down on a very long sort of protocol, and lots of people are going to have to look at that protocol and make sure that what I’m saying makes sense. Make sure that it’s safe. Then even when you’re on a clinical trial, you have a thousand eyes looking and making sure that everybody is safe in doing these things, and that the research is being conducted in a manner that is appropriate. I think that for that reason, clinical trials are highly vetted as a way, like I said, by many, many people, and so I think any time is a good time during the course of one’s disease to participate in a clinical trial.
Brian Brewer: I think it’s very fascinating that you actually say that because clinical trials are often perceived as a last resort, whereas what you’re saying, at least in prostate cancer is, consider all your options and you might respond to something rather than whatever the standard of care is. So that’s wonderful to hear. I have another question, this this one is live from one of our viewers, James. He’s actually already getting immunotherapy treatment, and just wondering if he should continue to receive treatment, or at what point do you come off treatment or with immunotherapy? Does it go on and on with a trial? So very curious to hear what you have to say about that.
Dr. Ana Aparicio: Now, and while that’s a little bit of a tough question, because it kind of depends on the treatment, right? So in general, one continues on a given treatment until either one has, you know, excess side effects or it stops working. That’s sort of generally the way to go. There are some treatments that we might think of stopping a little sooner. I, for example, tend to stop chemotherapy a little bit early. I don’t keep going and going just because it can have cumulative side effects, but if you’re tolerating it well and it’s working to keep your cancer under control, then I would continue.
Brian Brewer: What about someone like one of our viewers actually, who is on immunotherapy and now is asking about, this is a gear shift here, but COVID 19? We know it’s top of mind for a lot of patients. We know a lot of patients aren’t getting the screening in advance because they don’t want to go to the treatment centers or hospitals. What would you say to any cancer patients who are newly diagnosed, but also has these concerns about COVID? Can they get the vaccine? Should they go for their checkups?
Dr. Ana Aparicio: Yes. So you can get the vaccine, you can, and you should get the vaccine. It’s been looked at extensively in people with a diagnosis of cancer, and it is safe and there is absolutely no demonstration, because I’ve had people ask me this, and that are no evidence, not a shred of evidence that it makes the cancer work worse or grow faster or anything like it. It is definitely safe in people with cancer. All of the evidence to date supports that statement. In regards to the checkups, I think, you know, I think if there’s one thing that I think COVID has done for us is it has made us get pushed a little bit more into the 21st century when it’s come to virtual visits, et cetera, and so I think that virtual visits have become a tool that has is enormously useful, and I think that it will expand significantly our ability to conduct clinical trials safely. So I think that’s definitely a positive. Having said that, I tell this to everybody that walks in my clinic: If there’s something you can do at home, I want you to do it at home, I don’t want you to travel, I don’t want you to spend your time on my waiting room, I want you to be at home, but there are times when I feel like I need to see you, and so when I ask you to come in, it’s because it’s important for me to be able to sit in a room with you and actually see you and have this conversation. I think it’s important to know that certainly at MD Anderson, and I’m certain that at all other health care facilities, the safety of people is a top priority, and so we have gone to great lengths to make sure that any in-person visit is safe, and MD Anderson, it’s a big place, we see thousands and thousands of people and we really haven’t had any evidence that we’ve had any transmission in the clinic setting from any of the staff or any of the patients amongst them and in the waiting room. So I think it’s safe.
Brian Brewer: Well, that’s reassuring to hear for sure, and also interesting to see how this pandemic has changed the way medicine is practiced, and you know, I think one of the concerns about clinical trials that we’ve heard in these meetings that we’ve done is the number of checkups, the number of visits. How long do you have to stay on the trial? Now it sounds like you’re finding a nice balance between, you know, keeping people safe and comfortable at home versus having to come in.
Dr. Ana Aparicio: Right. Absolutely, and, you know, one of the things that I think is very interesting is I think clinical research, as we do it today is not how we’re going to be doing it in five years. I think we’re going to see certainly an increase in and certainly what are called patient reported outcomes through applications on your phones and Fitbits and things of that nature that are going to, again, I think, minimize the number of visits and certainly help us track better how people are feeling on these treatments.
Brian Brewer: That’s fantastic, I love embracing technology to make patient care better. So very glad to hear that you as you mentioned, also, many top cancer centers are doing this. Let’s get back to immunotherapy and prostate cancer. So there’s something called a cold tumor and something called a hot tumor. These are words that are thrown around. Can you explain what those are and what sort of impact does that have as a patient, thinking through his treatment decision with prostate cancer?
Dr. Ana Aparicio: So basically, a cold tumor is when, one of the things that actually I should mention and I think we were I’ve been enormously grateful to people that have volunteered to undergo tumor biopsies in the setting of clinical trials because that has truly signified a critical important thing for learning experience for all of us. Right. So, you know, just to sidetrack here for a second, but the hematologic malignancies, I think, are much further, you know, all the blood cancers are a little bit further in their molecular understanding, and that’s because they had they had access to the tumor and they were able to look at that carefully, and so basically, what a cold tumor means is that when you look at it, there are very few immune cells in that tumor, and so if you have very few immune cells, well, you can imagine they’re not going to be fighting that cancer very effectively. A hot cancer means that there’s lots of immune cells in there now. Not all immune cells are good cells, like we said earlier, but still if you have immune cells in there, then it’s easier to manipulate them to do what you want them to do, right? If you can activate the immune system, all you want, if the immune cells are not inside the cancer for whatever reason, then you’re not going to really have an effect. So prostate cancer has been considered a cold tumor for, I mean, or suggested to be a cold tumor for a long time. That’s true and not true in the sense that one of the things that happens with prostate cancer is that we call prostate cancer one name like it’s all the same disease and all 200,000 men that get diagnosed with it a year, and it is not the same disease in all two hundred thousand men that are diagnosed a year. So I think that, you know, we’re learning that there are subsets of prostate cancer that are, in fact, you know, pretty hot tumors, and you know, there are still some others that remain cold. It does look like, because prostate cancer goes to the bone most frequently, it does look like the bone is very good at keeping the immune cells away, and so and so that certainly has been a challenge. To some of those studies that are going on right now are looking at trying to open up that bone to the immune system, but not all prostate cancers are cold.
Brian Brewer: I’ve heard that prostate cancer might prefer metastasis to the bone. I’ve seen it our scientific director, Dr. Lloyd Old, died of this disease, which is just heartbreaking. So I know that that’s a very serious thing. Are you saying that there are some therapeutic strategies now being looked at that involve metastasis to bone, and are they immunological in basis or? Let’s hear more.
Dr. Ana Aparicio: They’re trying to manipulate the immune microenvironment of the bone to, you know, basically the bone is an immunosuppressive microenvironment, and so trying to make that switch so that you can turn off the suppression of the immune system. Then, you know, you have different types of I guess there’s lots of the immune system is very complex, and one that I cannot claim to be an expert in, but there’s many different ways of activating the immune system, if you will. What has been approved up until now have been these immune checkpoint therapies that basically kind of take the brakes off of those T cells to unleash them to go fight the cancer, right? But now there are a number of treatments that are trying to enrich the amount of cells and immune cells that get into the cancer. So there’s these what are called, for example, bispecific T-cell engagers, right, where one end of the drug sticks to a marker that’s on the prostate cancer cell, or whichever other cancer cell, and then another end of the drug sticks to marker that’s on the T cells, and so the idea is to bring those together. There’s all these CAR-T cells, et cetera, that are being looked into in various solid tumors, but also in prostate cancer. There’s just so many it’s hard to really summarize them all.
Brian Brewer: I mean, you mentioned car T cell therapy, bispecific antibody therapy. We heard about vaccines, the first approved FDA therapy to treat, immunologically, prostate cancer was immunotherapy. That’s zipless Lusail, as you mentioned. These are a lot of different categories. How is a patient supposed to navigate this, and how do you how do you broach all of these options to your patients?
Dr. Ana Aparicio: Well, I think that again, it has to do so, most of these are for me in my practice, and I’ll use, like I said, silty fairly early on in the course of metastatic disease with regards to the others is it really has more to do right now with the clinical trial availability. So each clinical trial is designed for a specific subset of the disease at different stages, and so whenever someone that clinical trial is available, most certainly if it involves an immunotherapy, I will certainly have a discussion with my patients.
Brian Brewer: So I’m detecting a theme here with you about the importance of clinical trials and really exploring those as options for you at any stage of prostate cancer diagnosis. That’s a conversation you should be having from the very beginning. I think that was very clear. So thanks for sharing that. Another question from one of our viewers is about genomic sequencing. What is it? When should a patient have it done? Is it done as a matter of standard of care or is it something that a patient has to ask for?
Dr. Ana Aparicio: So genomic sequencing, there’s two types of genomic sequencing, so genomic sequencing refers to looking for alterations in the DNA. Right? So there’s your normal body DNA and that’s what’s called germline DNA, and you inherit that germline DNA and you can have genes that are passed from parents to children.
Brian Brewer: Let’s explain germ line for the viewers, that’s the DNA that you get through inheritance that’s part of your basic cause, right?
Dr. Ana Aparicio: That’s your basic code. Every cell in your body has that DNA. So then there are sometimes some mutations that happen in that DNA that puts you at risk for having prostate cancer. It is standard of care to do germline screening for men that have metastatic prostate cancer. That’s one, and that’s important because it informs the risk of your family members and it informs the risk.., and actually, it puts you, you, you derive some benefit from certain drugs that you would otherwise not have access to. A separate thing is the tumor DNA. Right. So now the tumor DNA is different from your germline DNA. It has some features of your germline DNA, but it’s also DNA that’s gone wrong and there’s lots of mutations in that tumor. That requires a biopsy, that biopsy can be a solid biopsy, so they put a needle into it and they take out a piece, or it can be a liquid biopsy. It can be in your blood. We can look at circulating tumor DNA. Then each have its pros and cons. But we’re running out of time, so I’ll be brief. That tumor DNA is where you look at genes that are altered in that particular tumor, and those genes might make your tumor more likely to respond to certain therapies, amongst them immunotherapies, and there’s some studies that suggest that the amount of abnormal genes that you have in your tumor, what’s called a tumor mutational burden actually correlates or predicts the response to immunotherapies. So it’s very important, actually, to do genomic sequencing of the tumor and the germline. Both.
Brian Brewer: So again, is this something that an oncologist will do naturally or is this something that a patient needs to self-advocate?
Dr. Ana Aparicio: Well, they should. I mean, they should. The question is the timing, some people will want to do it with the primary tumor. I don’t think we’re certain how much changes with treatment, and so I tend to try to do the sequencing later on in the course of the disease, but either is appropriate. Wonderful.
Brian Brewer: We are almost out of time. This is such a big topic, so important to so many people. Let us wrap up by letting me ask you in your course as a as a doctor who treats patients, how has immunotherapy shifted or affected the way that you interact with your patients? Is there any good news or anything that you’d like to share with your patients who are experiencing this for the first time?
Dr. Ana Aparicio: Well, enormously, because I think that for the first time since we started using immunotherapy, we have actually started talking about cures in metastatic prostate cancer, and so I have seen some dramatic responses that are durable for good. Now that doesn’t happen in everybody. We still have a lot of work to do. Those are the, you know, few people that benefit to that degree, but it’s certainly something that has been very encouraging and really incredible to see. So yes, it’s changed.
Brian Brewer: That’s wonderful to hear. Dr. Aparicio, thank you again, so much for being with us today at the CRI Virtual Immunotherapy Patient Summit, our second day in a row. This is so helpful and I also want to thank the University of Texas, MD Anderson Center, for being a good partner and helping us spread the word about this important event. With that, those of you who are watching look for a poll, we’re going to be asking you what your biggest takeaway was from this session. I know what mine was, and Dr. Aparicio, again, thank you so much, and with that, let’s move on to the next segment.
Dr. Ana Aparicio: Thank you.