S1E3 | Clinical trials: Breakthroughs in cancer treatment

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This is a podcast episode titled, S1E3 | Clinical trials: Breakthroughs in cancer treatment. The summary for this episode is: Immunotherapy drugs that marshal the body’s immune system to fight cancer. Genomic analyses that examine cancer at the cellular level, allowing for precise treatments personalized to each patient. These and other breakthroughs have been made possible because of one little-understood, yet fundamental aspect of cancer care: the clinical trial. How do clinical trials work? What progress have they made? Why do so few patients enroll in them? And what is the future of cancer research in the age of COVID-19? Pat Basu, MD, MBA, President & CEO of Cancer Treatment Centers of America® (CTCA), and his guest, Arturo Loaiza-Bonilla, MD, MSEd, FACP, Medical Director of the Clinical Research Program at CTCA, answer those questions on this week’s Focus on Cancer podcast.

Pat Basu: Hi, I'm Dr. Pat Basu, host of Focus on Cancer, the show where we answer everyday questions about cancer and cancer therapy. Today, I'm extremely excited to welcome Dr. Arturo Bonilla to the show. Dr. Bonilla is the Enterprise Director of Clinical Research at Cancer Treatment Centers of America, and also a world- renowned expert in cancer clinical trials. And we're extremely excited to have him on the show. Dr. Bonilla, welcome.

Arturo Bonilla: Thank you so much for having me, Pat.

Pat Basu: Well, thank you for taking time from your busy schedule to be here. You know, we had a lot of momentum going into the COVID- 19 pandemic with cancer clinical trials, which is really the foundation of bringing new lifesaving therapies to bear. And I'm certainly concerned about the pause, the halting, and the diversion of resources away from cancer clinical trials during this pandemic. But nevertheless, very excited to get your insights and expertise on clinical trials. But let's start with something kind of broad and basic. Just tell us and our viewers, what is a clinical trial?

Arturo Bonilla: Yes. And that's a very, very important question because many of our patients and the viewers probably have heard the term, but they're really not familiar with what it really entails. So clinical trials are ways or methods of studying new drugs that are coming from the bench side, from the animal model to the forefront, to several patients. So it's the way we get drugs approved. They're currently available. So any single treatment option that is currently available for cancer and for any other kind of disease has go through the very rigorous process of clinical trials to show efficacy, safety, and the opportunity for patients to understand what's the right dose, and the intended benefits that come with each one of these treatment options. So it's the wave of the future. It's the way we are managing cancer now and how all these innovations are coming to the clinics through these clinical trials.

Pat Basu: So Dr. Bonilla, just to go deeper into that for patients who might be listening. Is it safe to say that most therapies today, at some point in the past, went through a clinical trial and most therapies in the future will also go through that path?

Arturo Bonilla: Absolutely. And that's right on point. As you know in the United States, we have the FDA, which is the food and drug administration and the agency that gives the go or no go to things to come to the market, to patients, et cetera. So every single drug that you have heard from, even from aspirin to the most advanced immunotherapy or CAR T-cell has gone through these clinical trial processes. So we can know exactly how the treatment works. And you may have heard now, the age of COVID, about vaccines and why it takes so long from them to develop. Even though we expect things to happen within less than a year, which is absolutely unheard of. We are still beta testing these vaccines in patients. So they have to be from the phase one, which is very early stage to all the way to the approval. And that's how it comes to the clinics and to get access to the general public.

Pat Basu: Got it. Thank you. And I know that you just went through sort of that definition and really covered the benefits of clinical trials. I certainly think that it is a critical component of not just the battle against cancer, but against so many other diseases. But can you outline again for our audience what would you sort of characterize are the top benefits of clinical trials?

Arturo Bonilla: Yeah. So clinical trials are good for a number of reasons. Of course, the first one is we are advancing science and that's how we know if a treatment works or not. And if it should be used. The other benefit for a cancer patient is that they may get access to a drug that is very promising, but it may take years to become available commercially. So you want to get it now and being part of the clinical trial allows you to get the treatment earlier. Not only that, but you have an extra layer of support for us to really have a clinical trial open. We need very well organize and dedicated team of physicians and research coordinators. And that's an extra pair of eyes that can look at your case, making sure that you are well taken care off, and you're well- treated in terms of safety, efficacy, checking up on you. And also is a way to pay it forward. Anything that gets benefit from this treatment not only helps you, but it's going to help future generations of patients just like you once those drugs that are available commercially. So it has a number of benefits that are not only personal, but also to society as a whole.

Pat Basu: Well, I definitely have spoken to many patients who have benefited from exactly some of those things that you mentioned, getting therapies earlier than they would have that led to lifesaving treatment, as well as those benefits of having an extra care team around them. Can you maybe give me a story of a patient that would really bring it home as an example of a patient that was benefited from a clinical trial in the cancer arena?

Arturo Bonilla: Yeah, so... Wow. So many examples of those responders to treatment. But one that comes to mind and I think was also the subject of a recent article that you wrote with inaudible and put in Scientific American I've seen is the Kids of Len. Len Archer, he became a real advocate for clinical research because of his own experience. He is a former firefighter. He was ready to enjoy retirement and live his best life with his wife. And he was hit with a diagnosis of a stage four pancreatic cancer. The same one that Alex Trebek from Jeopardy and others have suffered from. And we know it's a pretty devastating diagnosis. And there is really a lot of need for research. So a lot of our patients get into clinical trials. When he saw me, we decided to do biomarker testing. So looking at the DNA of his cancer and found something that is... It was called high tumor mutation burden. That means that there's a lot of typos on the DNA of that cancer. And the more typos if you activate your immune system, you can make the body fight the cancer on its own. In his case, he had a very high number on that TMB. We started the patient on an immune therapy treatment option. And in just a matter of a few weeks, he had what we call a complete response to treatment. And it's over two years now and he's still alive, well with no evidence of disease and able to live his best life as we spoke. And not only that, but a couple of weeks ago, we actually have an FDA approval for the same indication that we're talking about. So if he had not joined a clinical trial when he did, he may have not the chance to be on this drug that saved his life. And now he's saving the lives of many other patients because now it's commercially available. So there's always a great story to tell and hopefully more to follow.

Pat Basu: Yeah, it really is. I thank you for that. I had the privilege of meaning Len, a remarkable man and a remarkable story. And you're exactly right. And one of the things he told me was because of... Well frankly, he mentioned you by name and also just the idea that the clinical trial allowed him to get a treatment two years earlier than the rest of society would have. And that's a remarkable thing that we would love to have for our patients. It's one of the things that motivates me so much about this is sometimes we think of clinical trials as this research aspect or the numbers. But when you think about an individual patient being saved, it's very powerful and very inspiring for me. You know Dr. Bonilla, I tell a lot of patients that every single thing in medicine has benefits and has risks. And we talk constantly about looking for things where certainly the benefits clearly outweigh the risks. That being said, obviously, tremendous amount of benefits to clinical trials. But what are some of the risks of clinical trials?

Arturo Bonilla: Yeah. So in everything in life, there's a balance, as you mentioned. And we know that even though things are promising, not necessarily everything that happens is the way we tend to. And that's why they're so rigorous in having the [inaudible 00:09: 28 ], et cetera. So one of the things that can happen is unexpected side effects, right? So we always follow the profiling thing. You may have diarrhea, or you may lose your hair, et cetera, with certain drugs. But once in while in a low percentage of patients that may be the unexpected side effect that makes the patient either drop from this study or being unable to get the treatment on time, et cetera. So that's one of them. The other concerns a patient may have is, I'm being the guinea pig. Why are you giving me this? I'm going to get a sugar pill or water on my infusion. And something that has changed, and I wanted to clarify this for the audience, is that in cancer the use of placebos have really fallen out of favor over the last decade. Most of the clinical trials that are currently available, they're using the standard of care plus. Basically, you typically know what you're getting. Is just the clinical trial is the conduit to allow you to get another extra drug that make things better. And typically, you know exactly what you're getting and not. And a full description of the things that are in the protocol would be talked to you before you even sign up.

Pat Basu: So that's interesting. Let me just kind of go a little bit deeper into that. So if a patient is getting drug A and there's clinical trial on drug B, you might add drug beta drug A. But to what extent might that reduce the efficacy or the ability to determine whether drug B is really helping? Might there be interactions between the two drugs? Can you kind of speak about that sort of A plus B versus drug B versus a placebo?

Arturo Bonilla: Right? And that is all based on the design of the trials. And I think just to go a little bit before that is about phases. So there's different phases in research. So there's phase one, which is you're just finding the dose of the drug. You're not looking for efficacy. You're just trying to make sure that it's safe and you find the right dose. Phase two is you already know the dose. You're trying to look for overall safety. And some signal in efficacy typically is a single arm. That means that everyone the same. And it could be the combination A plus B. And the phase three clinical trial is when you're ready to prove that it's better than the currently available options. And that's when you made the differentiation. So you already know the safety profile of the combination of the phase two. So when you go into phase three, you're just trying to show the clinical benefit, which is a combination, the totality of evidence that includes not only the safety and tolerability of the drug, but also the positive outcomes in terms of shrinkage of the tumor, we call response rate, or prolonged survival, which we call PFS or OS oral survival. So it's always a very, very judicious rigorous process. And that's why we should do research always because that's the way to guarantee that everyone's going to get benefits.

Pat Basu: Thank you. Thank you for that. And that I think really helps clarify that. To end... To sort of zoom back out for a moment for our patients. I think they've now have a better understanding of what a clinical trial is, the risks and benefits, the phases. But walk us through the process. How does a patient find out about a clinical trial? How do they get accepted on the clinical trial? Can you give us some more insight into that?

Arturo Bonilla: Yeah, absolutely. And that's the rationale of why it's so hard for patients to get into clinical trials. If you look into cancer specifically between three and five percent of patients with cancer actually ever enroll in a clinical trial. And that is because it's not an easy task. It's challenging. And there's a lot of missing gaps in information which we're trying to solve. We really need to inform patients about it. So the first thing is, okay, you get a diagnosis of advanced cancer. We need to have a trial open, let's say in my office. And I sit down with the patient and say, well, we have the standard of care option. And there's also a clinical trial that includes that. But maybe there's a chance for you to get an additional drug that may help you to lose your outcomes or getting better results. And sometimes it's also based on a biomarker. A biomarker is something that we measure in the blood. Or we look into the tumor itself and it may tell us that maybe there's a drug that we can use to attack that specific weakness that we find on the cancer. So we have a very long conversation, typically about an hour with the patient. Where we explain every single detail of the protocol of the clinical trial. We have the research coordinator coming in to sit down with the patient. And then the patient signs consent. So that's called basically consent form. Once that happens, then it happens is the screening. A screening is basically going through the protocol and sure that the patient fulfills all those strict criteria that are part of the research component before you actually get the first dose of the drug. It takes about one or two weeks. In the most cases, what we're striving here at CTCA is to get that process actually fairly quickly. We try to get any less than a week, and we also prescreen the patients. So before they even show up in our door, we already have the clinical trial reviewed and ready to offer to the patients, so they don't waste time as we're doing this. And once everything has been vetted, et cetera, and all the check boxes have been done. Then we have the patient to come into the clinic and we start and then research ensues. So it's not a straight forward process. And it requires a motivated patient. But things that we're trying to accomplish now is to use technology to help us solve that. Maybe doing a prescreening technology to help patients match the clinical trial right away. And when the patient shows up at the door, they only need to just sign a consent. They already have information on the trial and they can make an informed decision in a quicker fashion. And also helping the sponsors running the studies understanding that how can we shorten those gaps and getting everyone involved in research. Because it's the way to help everyone. It's a win, win situation.

Pat Basu: It is. It really is a win, win situation. And I know from a physician's perspective and a societal perspective, we just need to find a better way to continue to improve, more matching and then getting more patients who can be helped by clinical trials onto those trials. So I'm going to come back to that in a moment, sort of the future and some of those things. But let's talk about the present right now with this foundation that you laid for us on clinical trials, Dr. Bonilla. Obviously, the world and certainly our cancer patients and all of us have been dealing with the COVID- 19 pandemic for the last several months. What impact has that had on clinical trials in the past several months?

Arturo Bonilla: Right. So COVID-19 has had a major impact in research. Of course, not only for cancer, but also for COVID as a disease itself. What we saw is a trade off. So cancer research took a major hit with many clinical trials being put on a hold because of patients being in lockdown. Patients' inability to come to our clinics or preferring rightly so to stay at home. And also because of disruption in global supply chains. And the sponsors tendiness to stop the clinical trials for the time being. In exchange, we saw a significant uptake on the number of therapeutic clinical trials for COVID. So looking for new treatment options for patients with COVID, various ways to diagnose them, and also a new number of clinical trials for vaccines. So we have seen once again a major disruption happening in the space, and that will be resonating and having an impact for a number of years from now. And hopefully, we can recover soon.

Pat Basu: Dr. Bonilla is it safe to say that during the COVID-19 pandemic that resources have been diverted away from cancer clinical trials towards more COVID specific research, whether that be a trial specifically or even just the search for a vaccine?

Arturo Bonilla: Yes. So all of the sponsors now are focused on COVID-19 research. So if they had something happening for other disease types, et cetera, they put a hold to many of them and changed priorities. Other things that are happening is that when we're not thinking about COVID, they may even think about competitive landscape. Maybe just there's what we call a [ me two 00:19: 00 ] molecule, which is similar to another one that is commercially available. But they still wanted to run the program and see if it worked. They stopped that completely. And now if they have a vaccine or a molecule that is really focused on COVID, they put all the resources on that and put a hold on all the things happening. So certainly a major shift in priorities that is probably here to stay until we get either the vaccine or a pretty good therapeutic.

Pat Basu: Yeah. And it's disappointing to me to hear because I absolutely, as I've said before, I think COVID-19 is a very, very serious pandemic. And obviously it's something that warrants our attention, warrants our precautions, warrants our safety. But at the same time, for me, it's also important to continue the battle on cancer and not take our eye off of it. And as I've said in the clinical realm, we have to continue to fight and care for our cancer patients. I would argue that in the research realm, we have to make sure that we do that the same. If we pause on these clinical trials, I think it could really have an effect. Could you maybe paint for us a picture if we were to reduce or halt cancer clinical trials, what might be the result of that three or four years down the line? Maybe less cancer, new cancer therapies, can you kind of show us what might be the consequences of this?

Arturo Bonilla: Yeah, absolutely. Well, we know for sure that if we hold the clinical trial now, first we are missing the opportunity for many patients to get access these drugs. So we have an immediate impact on current patients being involved. But this is an exponential shock after this. So the fact that we are holding all this research for the next six months to a year, it may take about three or four years to fully recover and get back to the track we were. It not only affects new drugs, et cetera, but also new biomarkers and new approvals because everything will be in backlog. So even the ongoing trials that we're ready to finish are [inaudible 00:21:20], they're having a hard time. So I couldn't even imagine a small biopharma or companies that have very promising molecules but they don't have the budget because they go into bankruptcy or they don't have the resources to spend it further. That's going to be felt for a number of years now. And hopefully we can improve that, but it's a challenge.

Pat Basu: I agree. Yeah, I think it is a challenge. And I agree that hopefully we can improve that. Along those lines let's talk about sort of hope for the future and improvements. What can we expect on the horizon? What are some of the kind of the bold innovations, or new technologies, or processes that might improve or change the clinical trial landscape in cancer in the years ahead?

Arturo Bonilla: Yeah. And that's what gets me excited about every morning when I'm trying to check for new emails or like are you interested in joining this clinical trial is because of those innovations. So first started with immune therapies and all the new drugs that are currently available, but the things that are really making a change and a dent in research is finding these CAR T-cells, or engineering those cells, or doing gene editing using crisper technology to make those immune cells way more active against cancer. So we're learning now of new, what we call off the shelf... Basically, you don't need to get your own cells extracted and trained to attack the cancer. We can just take someone else's cells that get expanded, and you can use it on your own. Like taking a pill and making it fight the cancer on its own. So that's a remarkable thing that I feel has been a change dramatically the way we treat cancer. And the combination of new drugs, looking at the DNA, about also what we call the packaging of the DNA, that's called the epigenetics or the epigenome of that, and linking it with new technologies for detection. So we here at CDC, we have a couple of programs for liquid biopsy. We can Doing detection of cancer earlier, or looking at very specific alteration of the blood stream that are key to either find in recurrence or figthing the cancer right away by finding those mutations. So that's a lot of the excitement happening. And lastly, they use the technology to accelerate those developments by using digital tools, wearables, and software that helps match patients or helps them to get treatment, even maybe at home or other. So things that we're learning everyday.

Pat Basu: That's really helpful. I share your enthusiasm about clinical trials and your optimism for the future in terms of what they may and will represent in terms of better therapies to fight cancer and save more lives. Dr. Bonilla, I'd now like to transition to some of the specific questions that we've received from patients. We have several here and I just want to pick some that I think we can get to. The first is from a patient who asks, I keep hearing the term personalized medicine, but I'm not exactly sure what it means. Is this a cancer treatment approach or something applied to patients overall? Can you talk a little bit about personalized medicine?

Arturo Bonilla: Yeah, absolutely. And that's actually a new topic and very close to my heart because that's what we do when we do a biomarker testing, but also when we're looking at the patient as a whole. So it's a little bit of both. So personalized means that is really focused on you as a patient, as an individual, with all of your humanity and characteristics. So it's not only about the cancer type or the biomarker that your cancer has based on X testing and the drug that works for it. But it's also about you as a human being, as an individual. What are your social determinants of health? What are the things that make you different? Or what are your current situations that make it into consideration when we're doing a clinical trial or when we're giving you a standard of care? So it's really a way to make it individualized and tailored to you and only to you to make it really effective and meaningful.

Pat Basu: Terrific. Thank you. Thank you. This is a question that keeps coming up, especially as the COVID- 19 pandemic continues to escalate in different regions around the United States. This patient wants to know should she put off her upcoming mammogram?

Arturo Bonilla: I would say depends on what kind of mammogram we're talking about. So if you have an average risk and you're just getting a mammogram as a follow up that because you had one done maybe a year ago, it's okay to wait for maybe a month or so, or something like that for screening. However, you don't want to put it off forever because there is always a chance that we may want to detect this earlier before it becomes a problem. If it's a mammogram because you just got diagnosed with a mass in your breast, you shouldn't put it off at all. You should continue your workup for your cancer and make sure that anything that you need to get done for the cure is performed in a timely fashion. So it's all about communicating with your doctor. Just call us. We can do telehealth visits. We can discuss with anyone involved. So you get the right care and there's no delays in your treatment. Because that's important.

Pat Basu: Thank you. This patient has a question that says a friend of mine was talking about a big trial that he just joined. And it was the second time that this patient had heard about it. It's called taper, T- A- P- U- R. And he said it had something to do with using existing treatments in new ways. Can you tell me more about this taper trial?

Arturo Bonilla: Yeah. So taper is a very large study that is what we call a basket trial. So a basket trial means that you are not put on a treatment specifically based on your tumor type, but you are put on based on the biomarker that your cancer has. So if you have biomarker X, you get into arm A and vice versa. So there's basically a very large clinical trial, which is very personalized focused on the biomarkers of your tumor. That clinical trial is open in many studies across the United States in many places. And is run by the American Society of Clinical Oncology, which is the largest society for oncology in the world. And we are participants of taper. And actually, Len, that we spoke earlier today, he was a part of the trial. And he's still a part of the trial. And he joined that inaudible arm, which is the one that is for high TMB patients. So it's something that we need to check first for the biomarker. But if you have the right biomarker, you can get access to those drugs in a different way. And hopefully better outcomes from that. So that's what taper is all about. And happy to discuss further. Please tell us to communicate with us. We'll be happy to have a conversation about the clinical trial.

Pat Basu: Terrific. And one more patient question here. This patient writes I've heard a lot about fast track FDA approval, especially when it comes to ongoing research. Can you tell us a little bit more about fast track approval, what that means? Is that something related to the COVID- 19 pandemic or is this a general FDA process?

Arturo Bonilla: He has a great question. Very informed question, actually. The fast track designation is a way for the FDA to get a quicker approval compared to the standard one. So the standard one requires a phase one, two, three, clinical trial, and to prove the benefit over many years, which could take six years or more. And the idea here is that with data from enough patients, which is the predetermined based on the a disease type because it's not only for cancer, then the FDA may say we see enough good results from a phase two clinical trial and will grant you approval now. So patients could get access to these very promising drug. However, you have to prove in a larger trial after this approval that I just gave you because it's an conditional approval. And it's to make sure that we continue that formal or full approval right after. So it's a very interesting and novel way to get access to drugs to patients when they have a rare tumor type, or a rare biomarker, or it's a really unmet need. So we're interested and excited to explore these studies further. But it's a very noble way to get access to these drugs. And I'm happy that we have that pathway available.

Pat Basu: Outstanding. Thank you. I'd love to conclude with any advice that you have for patients.

Arturo Bonilla: Yes, absolutely. So something I tell every single one of my patients is empower yourself with information. Be your own advocate to understand the treatment options ahead of you, including clinical trials and new options that are for you. Not only for testing, but also for treatment. I always say," Let's leave no stone unturned." The way we manage our patients, which is the mother of standard of care. It means that we are looking at them as if they're our family. And one of them is I want you to be in a clinical trial. I want you to get tested for these biomarkers. Because if you find them, we can have a difference in the outcomes. So always be informed and let's find ways to collaborate and research. I have no concerns about my patient going across the street to another investigator to have a better trial. And I try to do the same and have them come back when the time is right for all of them. So it's a matter of collaboration and always have to make sense to you, be well informed, and always talk to us because we're here to help you.

Pat Basu: Fantastic. Well Dr. Bonilla, thank you so much for coming out on the show. I know you're incredibly busy with clinical practice and leading clinical research and clinical trials. So very, very grateful for you spending your time, sharing your expertise with us. As I mentioned before, very optimistic about the future and a huge proponent of what clinical trials means in the battle against cancer. So thank you.

Arturo Bonilla: And thank you so much #ClinicalTrials.


Immunotherapy drugs that marshal the body’s immune system to fight cancer. Genomic analyses that examine cancer at the cellular level, allowing for precise treatments personalized to each patient. These and other breakthroughs have been made possible because of one little-understood, yet fundamental aspect of cancer care: the clinical trial. How do clinical trials work? What progress have they made? Why do so few patients enroll in them? And what is the future of cancer research in the age of COVID-19? Pat Basu, MD, MBA, President & CEO of Cancer Treatment Centers of America® (CTCA), and his guest, Arturo Loaiza-Bonilla, MD, MSEd, FACP, Medical Director of the Clinical Research Program at CTCA, answer those questions on this week’s Focus on Cancer podcast.

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