Personalized Cancer Treatment

In some sense, every person’s cancer is unique. However, for several reasons, patients are often treated in a one-size-fits-all manner, usually based on where their cancer is. Fortunately, recent advances in technology as well as treatments like immunotherapy, are starting to enable doctors to better tailor their treatments to their individual patients, based on what’s most likely to work in their specific circumstances.

In this webinar for patients and caregivers, Patrick Hwu, MD, of the University of Texas MD Anderson Cancer Center, discusses the advances in personalized treatment approaches for cancer. In particular, he highlights the promise and potential of combination immunotherapies and how biomarkers can be used to guide these strategies. In addition, Dr. Hwu also discusses the challenges that must be overcome in order to realize the potential of these personalized approaches.

Patrick Hwu, MD, is the head of the Division of Cancer Medicine, the co-director of the Center for Cancer Immunology Research, and the Sheikh Mohammed Bin Zayed Al Nahyan Distinguished University Chair at the University of Texas MD Anderson Cancer Center in Houston, TX.

As both a practicing oncologist and a tumor immunology researcher, Dr. Hwu’s goal is to translate basic immunological concepts into treatments that can benefit patients in the clinic. In pursuit of that goal, his work has provided important insights into our understanding of the relationship between tumors and the immune system, many of which have helped to advance clinical immunotherapy strategies, especially adoptive cell-based approaches. Most recently, he has focused on combining cellular and checkpoint immunotherapies, in addition to rational combinations involving other agents, in order to improve patient survival.

The "Cancer Immunotherapy and You" webinar series is produced by the Cancer Research Institute and is hosted by our science writer, Arthur Brodsky, PhD The 2019 series is made possible with generous support from Bristol-Myers Squibb and Cellectis.
 
Browse our Cancer Immunotherapy and You Webinar Series playlist on YouTube or visit the Webinars page on our website to see other webinars in this series.

WEBINAR TRANSCRIPTION

Arthur Brodksy, PhD:

Hello and welcome to the Cancer Research Institute Cancer Immunotherapy and You patient webinar series. Today is Friday, March 8th. And the title of today's webinar is Personalized Cancer Treatment. Before we begin, I'd like to thank our generous sponsors who have made this webinar series possible, Bristol-Myers Squibb with additional support from Cellectis.

My name is Arthur Brodsky. And I'm the science writer at the Cancer Research Institute, a nonprofit organization established 66 years ago with a mission to save more lives by funding research that aims to harness the immune system's power to conquer all cancers. This work has contributed to the development of lifesaving immunotherapies for a variety of cancer types.

And we present this webinar series to patients and caregivers to help them better understand what immunotherapy is and how it differs from other treatments, to provide information on the latest developments in research and treatment, and to connect patients to immunotherapy clinical trials. Now, it is my pleasure to introduce today's expert speaker.

Patrick Hwu, MD, is the head of the Division of Cancer Medicine, the chairman of the Departments of Melanoma and Sarcoma Oncology, and the co-director of the Center for Cancer Immunology Research at the University of Texas MD Anderson Cancer Center in Houston, Texas. As both a practicing oncologist and a tumor immunology researcher, Dr. Hwu's goal is to translate basic immunological concepts into treatments that can benefit patients in the clinic.

In pursuit of that goal, his work has provided important insights into our understanding of the relationship between tumors and the immune system, many of which have helped to advance clinical immunotherapy strategies, especially adoptive cell immunotherapies. Most recently, he's focused on combining cellular and checkpoint immunotherapies in addition to rational combinations involving other agents in order to improve patient survival.

This past November, Dr. Hwu received the prestigious honor of being named a Fellow of the American Association for the Advancement of Science. So Dr. Hwu, as you know, for too long, patients with a given cancer type have been treated more or less the same. But now we've come to appreciate just how unique each patient's cancer is, especially at the genetic level, which may partly help to explain why some of our one size fits all treatments don't work for a lot of patients with advanced cancer.

As a result, great efforts have been made, especially in the past decade, to develop methods to more precisely characterize individual patients' tumors in order to figure out what drives their activity and also which treatments might potentially work best against their individual cancer. In the end, the goal is to enable doctors such as yourself to tailor their treatment strategies to individual patients in order to provide them with the best chance of success.

So I'm very glad that we have you here with us today, Dr. Hwu, because you've been on the frontlines of many of these efforts that will hopefully help to improve the way patients are treated. So first, I'd like to talk a little bit more about some of the characteristics that can define cancer. So beyond where cancer is located, what other characteristics can help doctors better understand and treat an individual patient's disease?

Patrick Hwu, MD: 

All right. Thanks, Arthur. We're really happy to be here today. Let's first talk a little bit about what cancer is. I think that would help. The body is made of many different tissue types, for example, the heart, the lungs, the kidneys, liver. And each of these tissues are a little bit different than the others.

And each of these tissues are capable of causing cancer, or becoming a cancer. So what is cancer? Cancer is simply the cells of that tissue growing uncontrollably. And that's what takes over the body of the patients. And so depending on where the cancer is started from, that's how we usually define the cancer.

So cancer that starts from the liver cells we call hepatocellular cancer. Cancer that starts from the kidney we call renal cell cancer. And location is also important. But I think this gets confused a lot. So a lot of people say it's lung cancer. Well, there is cancer, usually caused by smoking, that can start in the lung. That's called lung cancer. But cancers can also spread.

So some people can have a cancer that starts in the breast, that would be called breast cancer, that then moves to the lungs. So we would call that breast cancer that has metastasized, or spread, to the lung. And so that's how we distinguish the cancers, usually from where they start. What organ did they start in? Because they're all different. And that's the first way we start to distinguish them to know what the best therapy is.

Arthur Brodksy, PhD:

So another big part of it, obviously– I think that, first, that was a great overview. I think cancer is, as you know, a very complex disease. And we kind of lump them into one thing. But really, a bunch of different things drive it. We've also realized over the past couple of decades, and especially recently, how important the role of the immune system is when it comes to cancer and its development and now its treatment.

So speaking of how the immune system interacts with tumors, I think now would be a good time to bring immunotherapy into the conversation, especially the checkpoint immunotherapies that have been relatively successful in several types of advanced cancer. What kind of characteristics– or biomarkers, as they're known. What kind of biomarkers can help determine whether certain patients might benefit from these checkpoint immunotherapies?

Patrick Hwu, MD:

So some cancers that start in some organs will stimulate the body's immune system. So with that specifically, we're talking about cells that we evolve, that help us fight viruses. Normally they're called T cells, T lymphocytes. And these cells are capable of finding a cancer, being able to recognize that cancer, and secrete enzymes to break holes in that cancer membrane.

And the cancer dies, and then the cell goes onto another cancer cell and does the same thing. It's what I call the kiss of death. So these immune cells are amazing. And they can live for years in the body. And so we've learned to harness that and take these immune cells a number of ways, activate them so they can go finding the cancer cells in the body, and doing the kiss of death to these different cancer cells.

So it's really been exciting. And because those immune cells can live for decades, oftentimes when we can get this to work, patients can be free of their disease for decades. So this works primarily in cancers that can stimulate the immune system. So what are some of those? Melanoma is one of those.

That starts in the pigment producing cells of the skin and spread to many parts of the body, including the lung and the brain and other parts like that. But the UV light causes a lot of those melanomas and causes changes in the DNA called mutations. And that makes those cells look very foreign, kind of like a virus to the immune system.

And so melanomas are stimulatory to the immune system. And we've been able to use drugs that take the brakes off our immune cells. And they've been very effective in some patients with melanoma that's even spread throughout the body. So that's one example. Another example is lung cancer, especially lung cancer that's caused by cigarette smoking.

Because the cigarette smoke also causes mutations or changes in the DNA that make the lung cancer look like a foreign body and a virus. And so we've been able to take the brakes off the immune cells with these drugs and allow these immune cells to then recognize the lung cancers, do the kiss of death.

And some of these patients are really free of disease for a very long time, because these immune cells can live for a very long time. So really, the first step is to try to find out, where did the cancer start? And that gives us a hint for which ones are what we call immunogenic, or able to stimulate the body's immune system.

Arthur Brodksy, PhD:

And if I understand correctly, also, these checkpoint immunotherapies, they help once the immune system has already recognized that tumor. So these tumors, these cancer types like melanoma, lung cancer, and I believe also kidney cancer, that have these higher numbers of mutations are also– it's not a direct correlation, obviously, but these are also more likely to have those T cells already recognize the tumor and infiltrate them, correct?

Patrick Hwu, MD:

That's right. And many of these cancer types, you named some of them, melanoma, lung cancer, kidney cancer, also bladder cancer, head and neck cancer, squamous cancer, not everybody responds to these cancers, but some patients respond extremely well. So out of these, some of the patients have really great responses when we take the brakes off the immune system.

Let's go into that a little more. What do we mean by taking the brakes off? Well, our immune system's amazing. It really keeps us free of viral infections. It won't forget a virus like a flu. We usually are cured from that over a few days because the immune cells can recognize the flu infected cells and keep us alive.

But these immune cells proliferate like crazy. And they themselves would become a cancer if we didn't have a system to put the brakes on. And so you can imagine immune cells are like tanks. They're tanks circulating in the body. And you can imagine, if we had a bunch of tanks protecting us on the streets, you wouldn't want those mortar shells to trigger automatically or too many tanks in there.

You'd have to put a brake on those tanks to make sure that they wouldn't harm anybody. And so when those immune cells get activated, our body typically shuts them down by putting brakes on the immune cells. And that's just normal. And that's good so that we don't get what's called autoimmunity. And you've heard of some really bad on autoimmune diseases, like lupus and others.

So what we've learned, though, with cancer, what we want to do is take the brakes off so these immune cells like tanks can be more active against the cancer and can kill the cancer. Now, we can get some side effects from that, so we have to watch that closely. But by and large, what we want to do in cancer patients is to activate their immune cells, these tanks, more so that they will be able to shoot bullets at the cancer cells.

Arthur Brodksy, PhD:

And one of those, obviously, I think the most– there's two, I guess, big brakes that have been approved. There's one, the CTLA-4, which, from my understanding, acts at a different level of the immune system. So the one I'd like to focus on is the PD-1, PD-L1 brake or checkpoint. And so another one of the biomarkers is, if the patients have this brake expressed in their tumors, they're more likely to benefit from these therapies that target that.

However, like you mentioned, just because they have all these traits that predict they might benefit, doesn't mean they will. And on the other hand, just because they don't have them at one analysis, just because those markers aren't there doesn't mean they won't respond either.

And so that brings me to my next point. Even though these therapies have helped patients with a lot of types of advanced cancers, unfortunately, they still don't work for the majority of patients and a lot of different cancer types. So what kind of strategies are being explored, within the context of immunotherapy, for these patients who might not respond to these immunotherapies alone?

Patrick Hwu, MD: 

It's a great question, Arthur. We need to figure out ways to get everybody to respond. It's really beautiful. My melanoma clinic, for example, used to turn over every six months because the prognosis was so poor. Now so many of my patients, I would say the majority, are living many years, having great quality time with their families, because we've learned to take the brakes off the immune cells and allow the immune cells to kill the melanoma, sometimes which is spread everywhere.

So it's really been remarkable. So we know it can happen. But it doesn't happen in many kinds of cancers, like pancreatic cancer, ovarian cancer. It's been very hard to get the melanoma or get these cancer types to respond to immunotherapy. So what could we do to get everybody to respond? I think one day we'll get everybody to respond.

But what do we have to do? I think we have to figure out where the issue is and why not. So I started saying that you have to first have immune cells that could recognize the cancer. Well, there's a specific receptor there. And I think in some cancers, like pancreatic cancer and ovarian cancer, we don't have enough immune cells that can recognize the cancer.

So we have to figure out, how do we get more immune cells recognizing the cancer? One way we're doing that is to try to take the few that are there, growing them up to large numbers, and then giving them back. We call that T cell therapy. We can also take blood cells from patients, put in receptor genes to allow them to recognize and hone in on the cancer, and that also is a way.

That's called a CAR T cell or a TCR transduced cell is a gene therapy. But it's another way to allow the immune system to recognize the cancer by doing T cell therapy. That's taking cells out of the body, either at the tumor site or from the blood, growing them to large numbers, making sure that they can recognize the cancer, and giving them back in.

It's like paratrooping troops in against the cancer. So that's one major way that I think we can get more patients responding. Another way is to enhance with vaccines. And so there's been a lot of trials now to try to make vaccines to stimulate these immune cells in the body.

I would say that's like training the soldiers in the body to proliferate to large numbers to raise an army that can then go in and attack the cancer. So that's what a vaccine is. And so I think those are two major ways that we might be able to get much more responses than we currently have. And hopefully, one day, we'll get all patients to respond.

Arthur Brodksy, PhD:

I hope that as well. And so one thing I just wanted to make clear to our audience is you've been talking about these different types of immunotherapies, but they don't necessarily need to be used alone. For instance, some of the checkpoint immunotherapies that we've been talking about in lung cancer specifically, they've been shown to– or at least lung cancer in addition to some other types, maybe, that aren't as far along– in lung cancer, it works better with chemotherapy.

And I know that you've also been involved in a lot of work that's looking at how different immunotherapies can work together and synergize to help give patients a better chance. So could you talk a little bit about the potential for combining these different modalities and how that might be able to help more patients?

Patrick Hwu, MD:

Yeah. That's a wonderful point you're making, Arthur. It's important to really put together rationally combinations of therapies that can work well. For example, we're also using targeted therapy. So what's a targeted therapy? Usually they're a form of pills, pills that you take every day. But what they do is they turn off the light switches and the circuits that cause the cancer to grow.

And so we're turning off, shutting down the circuitry. And a lot of times, what that does is it makes the area around the tumor– we call that the microenvironment. That's the fancy name for it. When we turn off these light switches, it makes that microenvironment friendlier to the immune cells. And so we can combine a targeted therapy plus an immunotherapy.

And we did that with BRAF and MEK inhibitor. Those are two forms of pills to block the signaling, the circuitry in melanoma. And when we added that to immunotherapy, we got a response rates over 70% in melanoma patients, patients with advanced melanoma. So that's a really exciting approach. So I think rationally putting together therapy such as targeted therapy plus immunotherapy is an exciting way to go.

Arthur Brodksy, PhD:

We've been talking about what signals to look for in the tumor and maybe what drives the activity which then informs what treatment approach you might take with a particular patient. But a lot of our viewers might be wondering, how do you figure out– how do you do that analysis and get those signals?

And obviously, I think the best way to figure out what's going on in a tumor is to do a biopsy and get an actual sample of the tumor itself. But this can also be a very invasive process and isn't always feasible or preferred for every patient. So what are some of the ways that are either already being used or that are in development for a potential use in the future when it comes to acquiring this important information about patients' cancers?

Patrick Hwu, MD:

So it's a very exciting area of study right now. The traditional way that we've done it is just looked. You just take a piece of the tumor, and you put it under a microscope, and the pathologist just looks at it. That's the traditional way that we can figure out what kind of cancer it is, are there immune cells in there? So we can just look. But there are other really exciting ways to understand cancers.

And one is to look at the genes, the genes that are mutated and change that cause the cancers. And that can tell us what therapies we can use. Such as the treatment I just talked about, the BRAF inhibitor and the MEK inhibitor that we used for melanoma, that we can only use in half of the patients, the ones that have the correct BRAF mutation and that have the certain signaling pathway circuit that's on.

Then we know what circuit to turn off. And if we have the right pill that turns off the circuit that we know is on because of the mutation doing a gene test, then that will tell us. Now, that's traditionally also done by a biopsy. But as you pointed out, biopsies require often interventional radiology to look at a scan and then stick a needle in. Normally, that's very safe.

But it'd be much easier to just get blood drawn. If we can just get blood drawn, that's much simpler. So hopefully, in the future, we'll just be able to get so much from blood. Because in the blood, tumors secrete DNA, parts of themselves. They break apart. Parts of themselves are circulating in the bloodstream. And we can start to detect tumor cells that are circulating as well as the DNA that they release.

And from that, we can get a lot of information. As these tests improve, it's going to be remarkable what kind of information you're going to get just by going to the doctor and getting your blood drawn. It's possible one day we'll get our blood drawn, I'll say, hey, you got a little colon cancer starting. We can't see anything yet, but you're going to need a colon cancer vaccine to try to get rid of this colon cancer that you don't even know about.

Arthur Brodksy, PhD:

Yeah. I think it's very encouraging the direction it's going in, not only from the diagnostic perspective but then how it might inform those treatments. And I also understand that these are a little bit farther down the road. But obviously blood contains a wealth of information. But also even from things like the urine and a patient's saliva, you can learn a lot, too.

And I'd like to turn just real quick– we can delve into a little more deeply in a later question, but specifically in melanoma, which you are really familiar with, we've recently found the impact of the bacteria in the lining of our intestines and how that can affect how a patient might respond to immunotherapy. I was wondering if you could share a little bit of those insights.

Patrick Hwu, MD:

Yeah. It turns out we're made of human cells, but we're mostly made of bacteria. There's so much bacteria in our mouths, in our colons, GI tract. And there's different kinds of bacteria in all of our bodies. And it turns out certain kinds of bacteria in the body will help the body respond to these immunotherapies and the cancers to shrink.

And so we're starting to understand that. And Jen Wargo from our group has done really wonderful work. I know she spoke on this series a few months ago. But really, it's some great work in trying to figure out which kind of bacteria is necessary. And we're starting to get some hints. But there's just trillions of kinds of bacteria, so it's quite complicated.

One thing we did find out, though, is we shouldn't just go to the grocery store and take a probiotic. Because that's probably not the right bacteria, and that will potentially crowd out the good bacteria. And so I wouldn't recommend that. One thing we're starting to look at is what we call prebiotics. And that's what you eat that changes the bacteria in your gut.

So it turns out, if you have a lot of fibers, such as you have in beans, that may feed the right kind of bacteria so that the bacteria in our gut helps us have an immune response against the cancer. It sounds crazy. But we do think that if you have the right diet, you may have better response to immunotherapy because of changing the microbiome.

It's extremely exciting research, but it's just at the beginning. There's a lot that we don't understand yet. But it's going to really be exciting. Definitely, after all these years of doing drug studies, and I still believe in got to find better drugs, I do think, I'm convinced, that food is medicine.

Arthur Brodksy, PhD:

That's extremely fascinating how the immune system itself is a very complex system, and it's still only one piece of the even more complex system that is our body, which includes, within a patient, the tumor, the immune system, and the bacterial cells, that I believe even outnumber ourselves, which is kind of crazy to think about. So now I'd like to turn– you alluded to them a little bit earlier– but now I'd like to turn to what I consider the ultimate potential when it comes to personalized immunotherapy for patients.

And that's personalized vaccines. So you mentioned earlier that all types of tumors accumulate mutations, which is what drives their activity and causes the abnormal behavior that we associate with cancer, I guess most directly the abnormal and excessive growth that defines cancer. And again, those biomarkers can help indicate which treatments might benefit a particular person.

But now, as you mentioned, those mutations, in addition to just driving that activity, they also physically make the cell look different. Whether it's some cancers are driven by viruses– not that that's a mutation, but it makes the tumor stand out. And even the mutations that they have within them make the tumor cells look different to the immune system and allow them to attack it.

And as you mentioned, in melanoma and lung cancer, with a lot of mutations, sometimes the immune system can naturally notice that it looks foreign and attack it and start the whole immune response against it. But in others, the immune system sometimes isn't as good at recognizing it spontaneously. And so that's where the personalized vaccines comes in.

Where now we're starting to see– I think the past couple of years the first trials started– where we can literally see in which unique mutations a patient's tumor has and then tell that patient's immune system exactly what mutation's the target. So the idea would be to target only the tumor and then leave the healthy cells. So could you share with us this exciting field of personalized vaccines and where it is right now and where it might be going?

Patrick Hwu, MD:

Yeah. So it's a very exciting area. As you know, every year, we make a different flu vaccine. Why do we do that? Because the virus is different every year, so we have to make a different kind of vaccine. And every person's cancer is different from the other person. So if we can really understand those differences and understand what the immune system might be finding, we're learning ways to do that.

We can make a vaccine or a T cell therapy and provide those cells that will then just kill the cancers and not the normal cell. So that's the key to having a non-toxic therapy, is to kill the cancer cells without hurting the normal cells. And the best way to do that is to target against the changes in the cancer that are unique to that cancer but not on normal cells. And so that's where we have personalized vaccines.

There's a number of groups trying that right now. I think it's a very exciting way to go. Also personalized immune cell therapy, where they take T cells against specific changes on the cancer and personalize that. We can also have some personalized approaches that are also a little more scalable, in my opinion, where we can have a cancer looked at closely and the tissue type of the patient looked at closely.

And then we'll pull off the shelf many different kinds of vaccine products, and then do a vaccine. Or T cell products, and give that to the patient. And personalizing it, but also having more off the shelf reagents, which may be more scalable to the masses of people that have cancer.

Arthur Brodksy, PhD: 

And just to follow up on that, just to kind of clarify what you mean by the scalable approach, it's that a lot of mutations are random. And they could affect any of the thousands of genes in our body. But there's some genes, the oncogenes and then the genes that would help tumors grow or genes that might stop tumors from growing, those are kind of what you mean with the scalable approach, right, these mutations that might occur in multiple patients?

Patrick Hwu, MD: 

Yes, like BRAF, KRAS, p53. Now, there's a number of mutations that can happen. And they interact very differently with different kinds of tissue types. But still, it's finite, the number of potential T cell receptors that we can have on the shelf or vaccine products that we can have on the shelf. And so then if we have what I call a warehouse of antigens or vaccines or a T cell receptors, we can then do T cell therapy or vaccines fairly rapidly in patients.

A patient can come to our office, we can take a look at– now, we're doing research, and we still have to build these warehouses. But ultimately, we'd hope that someone could come to the office, we check their tissue, we check the characteristics of the mutations, of the expression levels of the tumor. And then we pull the right things out of the warehouse.

And we either give a vaccine or a T cell therapy fairly rapidly, within a couple of weeks. So that's the goal. Because whatever we come up with has to be scalable to the masses. Because just in the US alone, 500,000 people a year die of cancer. So we've got to be able to, once we come up with these therapies, scale it to the population in an affordable way.

Arthur Brodksy, PhD:

I agree. So now I wanted to turn to clinical trials. And obviously, much of what we've discussed today highlights the promise and the potential of immunotherapy. I think we've discovered a lot. And enough of the treatments have shown promise that I think a lot more people are on board with immunotherapy.

Now, we really think that it can make a significant difference for potentially all patients in the long run. But as you mentioned, there's still a lot that we don't know and a lot of questions that we have to answer. And a lot of these questions, as well as the new therapies that we're using to try to help more patients, are evaluated and fine tuned in the context of clinical trials.

Also, when it comes to biomarkers, as we've talked about the different ways to measure them as well as which are the best biomarkers, those are still outstanding questions, too, that we need to answer with the help of clinical trials. So in light of that, could you talk a little bit about the importance of clinical trials and the critical role that they play in helping doctors such as yourself answer these most pressing questions that are needed to advance the field and improve care for patients?

Patrick Hwu, MD:

Thank you. Clinical trials are essential. All of the progress we've talked about today wouldn't have been possible without clinical trials. Also the clinical trials will give patients the best chance at the best outcome. Because it's always the new stuff. The old stuff's been around for a few years. But the new stuff's always present in a clinical trial.

I can't tell you how many patients I have that are doing great after years, but the only reason they were cured was because they got on the cutting edge clinical trial at the right time. And so the right clinical trial will save many, many lives and also help us give the best therapies. I always say, each patient that we see, we want to give the best therapy today that we can possibly give.

And we want to develop, at the same time, better therapies for patients that come tomorrow. So that's what clinical trials allow us to do. So another point you made was, which clinical trials and which agents? Well, that's really important. That's where biomarkers come in. We really want to be able to figure out, for this patient, we should give this drug. For this patient, we should give a combination of drugs.

For this patient, we should give multiple drugs. Now, we might have some toxicity, but they should get multiple drugs. But for this patient, we only need to give the single drug. And we'll have less toxicity. So that's where the future status is. And that's where we are working on biomarkers, to try to understand what it is about the patient as well as their cancer to allow us to give the right drug combination that will be the least toxic and the most effective against their cancer.

Arthur Brodksy, PhD:

It's good to hear. I just wanted to raise, I think you mentioned it, it's a very important point that, while these are new therapies, they are, in some ways, what the best and brightest minds in the field think are the best chances. And so I think there's a myth out there that sometimes patients are going to be treated with placebos. And that's not the case. Correct?

Patrick Hwu, MD: 

Yeah. Well, sometimes there's placebos involved in the big phase three studies. But for the most part, they're not used all that much anymore. And the reason for that is the science is just so good. We understand what turns on and off the immune system. We understand what turns on and off cancer cells, circuitries.

And so the science is so good that the products that we put into trials have a decent likelihood of helping patients. And for that reason that the phase one, phase two, we don't even use placebos a lot of times. In fact, patients are on the drug and we just look at the response rate, what the toxicities are, and how well the cancer shrinks or not and how well the patient does in the long run.

Our goal is to get every patient on what I call the tail of the survival curve, meaning healthy and happy 10 years from now, 20 years from now. My patients, I always tell them, we're trying to get you into the 10 year club. And some of them were trying to go for the 20 year club or the 30 year club. And that's the goal. And that's the potential promise of immunotherapy, because these cells survive in the body for so long.

Arthur Brodksy, PhD:

And I think another thing that I've heard a lot with clinical trials is some people think that they're just the last resort, that you go to them if nothing else works. And obviously, there are clinical trials that do focus on those patients for whom nothing else has worked yet. But also now, immunotherapy clinical trials are also exploring immunotherapy earlier in the process of cancer. So patients who don't necessarily have advanced metastatic cancer that hasn't advanced and everything, we're starting to apply it earlier in the treatment, correct?

Patrick Hwu, MD: 

Yeah. The best opportunity to cure a patient is the first time with the first therapy. And so, for example, in melanoma, a clinical trial that just read out recently was that if we cut out the melanoma but it had spread to lymph nodes, and we cut that out, the patient's still at risk for recurrence. No disease on the scans.

But if at that early time point you give immunotherapy, you can greatly decrease the chances of the melanoma coming back and increase how long patients live. And so if you get them earlier, it's much better, the immune system is healthier. And so I think that is a correct point. We really want to start these really wonderful clinical trials early as the first therapy if possible.

Arthur Brodksy, PhD:

And to go back to your analogy earlier about the immune system in the army, it would kind of make intuitive sense then that, if cancer is the opposing army, you would want to eliminate– you mentioned taking out the melanoma with surgery first. When those numbers are low of the cancer, I would think the immune system would then have a better chance, potentially, of eradicating it as opposed to fighting a huge tumor all at once. Is that correct?

Patrick Hwu, MD: 

Absolutely. Because the enemy army not only makes more cancer cells but also produces things that inhibit the immune system. So what we've done is two approaches really. The first approach we talked about. You cut out the tumors, and then you give immunotherapy to try to prevent it from coming back. The other we call neoadjuvant therapy, where we give immunotherapy and then cut out the cancers to try to stimulate the immune system first and then cut out the cancers. And that also has been working quite well.

Arthur Brodksy, PhD:

Great. So we're almost out of time. But at this point, I'd kind of just like to throw out an open ended question to you, or rather just give you a chance to lay out your vision for this field, not only where we are now but where you think it might be going in the future and the hope that it could potentially provide for patients.

Patrick Hwu, MD:

I think right now we've already established that, in some cancer patients, immunotherapy works very well. especially in patients with advanced melanoma, for example, not everybody, but in many cases, we can get a very good result. So the future is to take patients and try to figure out who's not responding right now, what kinds of cancers, how do we get all ovarian cancer patients to respond, pancreatic cancer patients to respond?

Also the melanoma patients that aren't responding so well or have a response to then have a recurrence. How do we get everybody to respond? It's our dream, and I think a very realistic one, that a few decades from now, people just shouldn't be dying of cancer. That we know so much, the science is going so rapidly, that we should be able to detect through blood tests and other things someone's cancer very early and intervene early and prevent it so that people don't even get cancer.

We should be able to figure out what we should do for our diet and the environment and exercise and other things to try to prevent cancer from coming on in the first place. So there's going to be many ways that, hopefully, in a few decades, we're not going to have patients dying of cancer. It'll be unusual. I'd be like someone dying of pneumonia now.

Oh, they died of cancer? That's unusual. And that'll be a few decades from now. But we can squeeze that even closer and make that even a sooner reality if we all continue to support cancer research. Because that's extremely important. So the CRI and other groups have really been strong supporters of cancer research. And it's extremely important. Because that way, we can make that dream a reality sooner.

Arthur Brodksy, PhD:

I share your optimism. Like you mentioned, obviously the end goal is to save lives and help improve care for patients. But it all starts with the research, the basic research in the labs that helps build that understanding that then we can base the treatments off of, which I think is a very important point.

So that is all the time that we have for today. Thank you very much for your very informative and inspirational webinar, Dr. Hwu. For more of our webinars and additional resources we have for patients and caregivers as part of CRI's Answer to Cancer educational programs, we encourage you to check out our website at www.cancerresearch.org.

Here, you can read and watch stories shared by others who have received immunotherapy treatment across a wide variety of cancer types. You can register for one of our upcoming immunotherapy patient summits, browse our entire library of past webinars featuring the world's leading immunotherapy experts such as Dr. Hwu, access information on other resources including treatment, emotional support, and financial assistance, and find help locating an immunotherapy clinical trial.

Finally, I'd like to thank our sponsors one last time for making this webinar series possible, Bristol-Myers Squibb with additional support from Cellectis. And again, you can watch this and all of our other webinars on our website at cancerresearch.org/webinars to learn more about immunotherapy options and a number of cancer types. Dr. Hwu, I just want to thank you so much again for taking the time with us today and for the amazing work that you are doing on behalf of patients. We wish you the best of luck.

Patrick Hwu, MD:

Thank you, Arthur. I had a great time today.