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Dr. John Leonard (Host): Welcome to Weill Cornell Medicine, CancerCast; conversations about new developments in medicine, cancer care and research. I'm your host, Dr. John Leonard. And today we will be reviewing some of the latest updates from the 2021 American Society of Clinical Oncology or ASCO annual meeting. ASCO is the world's leading organization for physicians and oncology professionals, caring for people with cancer. For the second year in a row, the annual meeting is being hosted virtually. ASCO's annual conference connects oncology professionals from around the world to discuss the newest state-of-the-art research and treatment guidelines.

Our guest today is Dr. Manish Shah who is a Fellow of the American Society of Clinical Oncology, Director of the Gastrointestinal Oncology Program and Chief of the Solid Tumor Service at Weill Cornell Medicine and New York Presbyterian Hospital. Dr. Shah has also served on several ASCO leadership committees, including the cancer education committee, and he is past chair of the ASCO clinical guidelines committee.

Together Dr. Shah and I will review some of the most significant research findings from the 2021 meeting. Dr. Shah will discuss updates in solid tumor oncology and toward the end, I'll give a few mentions of some updates in hematologic malignancies. So, Manish, it's great to have you here. I think this has become a bit of a tradition for us. You've done this before with prior meetings. Let's start with for our audience that's less familiar with ASCO meetings and other similar medical meetings, give everybody a flavor of the importance of this meeting in our field and what it does to impact cancer care.

Manish Shah, MD (Guest): Sure. Well, first of all, thanks John, for having me back, it's always a pleasure to be here. And it's terrific to talk to you, and have this forum. So ASCO, the American Society of Clinical Oncology is the primary sort of membership society for clinical oncology care. And every year there's an annual meeting. It's normally held in Chicago. Although this year it was virtual where 40 to 50,000 people join and it's where they can actually get updates on the latest findings with regard to new drugs and drug development, practice changing research and also where they can get a refresher on how to manage certain diseases.

There's a lot of education that happens at ASCO. And then finally, it's a great forum for researchers to meet to generate new ideas, new study plans, and to even meet and interact with the pharmaceutical industry, which actually does a lot of the research for clinical oncology.

Host: So, I want to start with some of the most impactful studies and the plenary session. And just for the audience, at ASCO and other major medical meetings; the top abstracts or submissions that come in every year presented at what's termed a plenary session. So, there may be hundreds or in the case of ASCO, probably thousands of poster presentations, where people walk around and talk, oral presentations that are oriented toward different diseases and then the plenary session really highlights a handful of presentations that are really the most important in the whole field; deemed so important that everybody, regardless of their area of specialization should hear about them. And so this is really kind of the cream of the meeting, so to speak as far as most impactful presentations.

So, why don't we start with some new developments at a presentation at the plenary session in prostate cancer, and the idea of a radio-labeled treatment for prostate cancer and our colleague at Weill Cornell Scott Tagawa was involved in this sort of area. So, why don't we talk about that first?

Dr. Shah: Sure. Yeah. So, of course you're referring to the Lutetium PSMA 617 study, which was also known as the VISION study. And this was actually kind of the culmination of years of research that in large part, as you mentioned, was led here at Weill Cornell. And by our colleague, Dr. Scott Tagawa. So, PSMA is also known as prostate specific membrane antigen. And this is a protein that's actually on prostate cells and also therefore on prostate cancer cells as well. And Lutetium 177 is a radioactive sort of isotope that is tagged to a antibody that binds to PSMA. And by doing that, it actually can deliver radioactivity directly to any cell that has PSMA on a cell surface, like prostate cancer. So, this was a phase three study examining standard of care treatment with this drug antibody conjugate Lutetium PSMA 617 compared to standard of care alone. And one thing that I should mention is that this particular Lutetium 177 molecule is radio leveled with a beta and gamma emiter, or which is to 177 lutetium molecules. So, this type of emiter kind of has specific characteristics in terms of how depths and how many cells around it can be affected. and, of course this was a large study. So 831 patients were randomized and patients who received the lutetium PSMA 617 plus standard of care had an improved overall survival compared to standard of care. And we look at median. So the average survival for the group it was 15 months versus about 11 months with standard of care.

So a four month improvement, which may not seem like a lot, but the other way to think about it is what we call a hazard ratio or the likelihood of actually having an event in this case, dying of the disease. And so the likelihood of having an event with lutetium and standard of care treatment is actually .62 or 38% less than with chemotherapy, or standard of care alone. So, this is certainly practice changing and something that our general public should know about because it's a new treatment for a very common disease in United States. And it actually kind of for me, it highlights the real benefits of what we do in terms of drug development and over time, we can really impact patient's lives.

Host: Yes, this is something that our team, as you mentioned at Weill Cornell, has been working on a long time. And PSMA is a target on prostate cancer cells, as you've mentioned, that really has been looked at in a variety of different types of therapy, radioactive therapy as in this study versus other antibody approaches and drug conjugate approaches, imaging approaches. So, certainly PSMA is something that is quite relevant it seems for patients with prostate cancer to be aware of, and again, a whole array of different ways of targeting it.

So, thanks for mentioning that. Another study that was presented was related to women with breast cancer and an approach of looking at a drug called olaparib as part of neoadjuvant chemotherapy in certain patient populations with early stage breast cancer. So can you tell us a little bit about that study?

Dr. Shah: Yes, absolutely. It was called the Olympia study. So, this is also practice changing. So, relatively recently a new class of drugs where approved for breast cancer called PARP inhibitors. So one of the drugs is olaparib, and the other drug is rucaparib and there's another one as well. But the point of this class of drugs is that in patients with breast cancer and other cancers that carry a mutation in BRCA one or two, this class of drugs can have significant benefit. The BRCA one or two are proteins that repair DNA and as cancer cells sort of divide if they lack these repair mechanisms then they become vulnerable to PARP inhibition and olaparib is a PARP inhibitor. And by providing the drug, you can actually kill some of these cells that carry goes to mutation. So, the OlympiA study was an adjuvant study, as you mentioned. It examined in 1,836 patients, the role of a olaparib versus placebo for one year after standard of care treatment.

So standard of care treatment for breast cancer involves either preoperative chemotherapy or postoperative chemotherapy and radiation for the majority of patients. And at the conclusion of all that treatment patients were then enrolled on this study to receive either olaparib 300 milligrams, twice daily or placebo.

And the primary end point of the study was to improve the disease free survival interval. And it was actually quite significant. So, these were all patients who had carried a BRCA one or two mutation, and the patients who received the Olaparib had a disease free survival of nearly 86% at about three years following study entry versus 77% if they received placebo. So, we mentioned the hazard ratio, the idea of the time to having an event in this case, the event is recurrence. And if you received olaparib you're chance of not having a recurrence was 42% better than if you didn't have olaparib. So it was really a sizable difference.

And almost certainly this is going to be practice changing. Patients, you know, moving forward, patients who have a BRCA one or two mutation will likely receive olaparib in the adjuvant setting, following their standard of care treatment. So again, really a wonderful study and congratulations to the investigators who performed it.

Host: before we move to the next study, one thing that you referenced was the concept of disease free survival. And I want to ask you your take on that concept. We're recording this in the middle of ASCO. And there is on social media a number of people have talked about this, and it's obviously an important topic as we think about study design. So, the concept of disease free survival, as opposed to overall survival which is how long people live, disease free is obviously the time that you're without disease before you, you relapse. So, Manish, I want to ask your sense of that as an endpoint and kind of the pros and cons of that as an end point, because this seems to be an important parameter that's being monitored in studies. It would seem to many people that, being disease free is a good thing. And that should be something that we strive to do. But why is that at least a little bit of a controversial topic in some settings?

Dr. Shah: Yeah. That's a great point. And thanks for mentioning that. So, I'll start off with the reason for why people actually look at this parameter and then I'll maybe highlight some of the controversy around it. The main reason why people use this parameter is because unfortunately for many patients with solid tumor cancers, like breast cancer, prostate cancer, if the cancer does relapse or recur after having some type of surgery or definitive therapy, then for most patients, that will ultimately lead to the patient's death from the cancer. So, having a relapse of the cancer will lead to dying of the cancer eventually over time. So, the disease free survival then becomes a surrogate for the thing that people care about, overall survival.

You know, we all want to be cured of our cancer. If we can predict earlier that we will, or won't be cured, then we can actually have the results and understand the impact of the drug earlier. So, instead of waiting six or seven years for results to have a mature overall survival end point, you might have to wait only three or four years to see that the patient in group A, had a longer time to disease free survival than the patients in group B. And that could lead to actually an approval of the drug earlier and allow more patients to benefit from the drug. So, there are real advantages to looking at disease free survival, because you can get kind of the answer you want earlier in the course of drug development and then allow for patients, if you have a positive study to receive the drug earlier, if the FDA approves it. But I think you mentioned kind of the controversy, and at least on social media, what I saw was sort of this idea that disease free survival is not an endpoint that patients care about.

They care about surviving the disease and I think to a certain extent that's true. So, these studies that report disease free survival should in fact be followed for overall survival, just to confirm that what we said before is true later. And in fact you know, in the OlympiA study, I focused on the primary end point, the disease free survival.

They did have, it wasn't mature data. They only had about 160 events for survival. But even in that smaller event rate, they were able to identify that olaparib did have an improvement in overall survival as well. But maybe not as significant. So, it was a 32% improvement, not a 42% improvement in overall survival. But the point is that it does track. So, improving disease free survival should improve overall survival. And that's, I think some of the kind of discussion points around that.

Host: So, there was an interesting study in the plenary session for patients with renal cell carcinoma which is commonly treated with surgery or nephrectomy looking at pembrolizumab an immune checkpoint inhibitor versus placebo. What's your take on that trial?

Dr. Shah: So, this is actually another study where the primary end point was disease free survival. And here we don't have the overall survival endpoint. This was a study of as you mentioned pembrolizumab, which is an immune checkpoint inhibitor. I think I'm sure your audience is aware of this new class of drugs. Maybe I shouldn't call it new. It's been around for some time, but it's, I think remarkable that instead of attacking the tumor itself, this class of drugs actually attacks the interaction of the tumor and the microenvironment to the immune system. And if you can block the signals that turn off the immune system, you can then activate the immune system against the cancer and that's what pembrolizumab does.

So, pembrolizumab is active in renal cell cancer. And in this study what they looked at is after actually doing surgery to remove the renal cell cancer, is there any benefit to using pembrolizumab in the adjuvant setting where there isn't actually known disease and this was a large study, 994 patients were involved and they were randomized one-to-one to receive pembrolizumab or placebo and the disease free survival was significantly improved in the pembrolizumab arm. Again, the hazard ratio for the time to event analysis was 0.68. So, that was a 32% improvement in patients not having a recurrence or not having an event compared to placebo. So, this is really a very important study that is likely to be practice changing as well.

I mentioned that they didn't meet their overall survival data wasn't mature. In fact, they only had very few events and even with that very few events, their hazard ratio for overall survival was assessed to the beneficial with a hazard ratio of 0.54. But I should mention that the two year survival rate was 97% versus 93%.

We don't have mature data for survival, but it's suggestive. That disease free survival is improved with pembrolizumab and likely therefore this should be a new standard of care as well.

Host: I now want to move to a less common, but obviously important subtype of cancer, some data in patients with nasopharyngeal carcinoma. So, maybe first kind of highlight what is nasopharyngeal carcinoma, for those that haven't heard of it as a specific entity unlike things like breast cancer and prostate cancer that we've talked about. And then the new data looking at combining a newer drug to chemotherapy in this setting.

Dr. Shah: So, nasopharyngeal cancer is one of the head and neck cancers and you know, it's actually endemic in parts of Southeast Asia and Southern China. But we do see it here in the United States and across Europe as well. It's associated with smoking, but also associated with a virus, the Epstein-Barr virus. And it's essentially a cancer of the oropharynx and the sinuses, the nares, those kinds of things. Most of these cancers are squamous cell cancers. And you know, as you might imagine, based on where the location is a lot of very important functional you know, your ability to smell, to swallow, to breathe. All that stuff happens in your nasopharynges. So, the ability to treat these cancers is very important.

The standard of care for patients who have recurrent nasopharyngeal cancer after a definitive surgery or chemo, radiotherapy they receive gemcitabine and cisplatin. These are two chemotherapy drugs. The new drug that you mentioned is toripalimab. It is another PD1 inhibitor, which is an immunotherapy checkpoint inhibitor like pembrolizumab. It's a next generation drug and this was examined in a randomized study of chemotherapy with, or without toripalimab. And it was actually quite significant. So, they looked at progression free survival, which is the time that you're able to receive the first line treatment. And what they found is that the progression free survival was really quite significant. At one year, meaning the number of people who were able to continue on treatment without progression with chemotherapy and the checkpoint inhibitor was about 50% compared to about 27% with chemotherapy alone. So, the hazard ratio was about 0.5, which is really quite significant. And the overall survival, it is a little bit early for those results. But at two years, the overall survival was about 78% with chemotherapy and the checkpoint inhibitor versus 63% with chemotherapy alone. So, the hazard ratio, there was 0.6 or a 40% improvement in reducing the risk of dying of the disease. So, again, very important study. I think this was a theme at this year's ASCO where checkpoint inhibitors remain a practice changing kind of novel treatment that is emerging across a lot of the solid tumors.

Host: So, I now want to move to one of your areas of focus you, as we mentioned earlier, direct of the GI Oncology Program at Weill Cornell and New York Presbyterian. And one of your areas of interest is esophageal cancer. So, there were a couple of studies. The second one you led, but first why don't you give us your take on the Checkmate 577, how cute the names of the checkpoint inhibitors studies, or at least some of them have this checkmate theme. But this is a study that I think was updated looking at people with esophageal cancer after chemotherapy, radiation and resection. So, tell us about that and how that changes practice.

Dr. Shah: Yeah, we were just talking about immunotherapy and checkpoint inhibition in nasopharyngeal cancer and renal cell cancer. In the same vein, in esophageal cancer there is modest activity of a checkpoint inhibitor. The Checkmate 577 study was a study in the adjuvant setting. So, the standard treatment for esophageal cancer localized is to do chemotherapy with radiation followed by surgery. And with that standard treatment about 20 to 30% of patients will essentially not have recurrence and do very well. A lot of patients will have some residual disease in the surgical specimen and in that population, the investigators examined the role of nivolumab, which is another checkpoint inhibitor versus best supportive care or placebo and patients who received nivolumab had a significant improvement in the disease free survival with adjuvant nivolumab.

So, it was kind of the theme here that if you're able to activate the immune system for micro metastatic or microscopic disease, you can prolong the disease free survival. This study, the overall survival was not yet reported but it was really quite a significant improvement in disease free survival. About 20 months worth. So, it is likely to be improvement in overall survival as well. So, at ASCO, this year, there's an updated dataset for this study which just highlighted the benefits of immune checkpoint inhibition in esophageal cancer.

Host: It seems like, as you referenced the theme. I mean, if you go back a couple of years, the immune checkpoint inhibitors, the initial data were really in primary therapy. And now we're seeing many studies looking at this aduvant kind of after surgery or after definitive therapy to try to reduce recurrence. We've got some positive studies, at least by some parameters. It seems like this is really kind of the next step and probably a lot more patients are going to be getting these drugs based on the fact that there are more and more scenarios where they seem to offer some benefit.

Dr. Shah: Yeah, I think that's exactly right. That's a great point that you make. In drug development, oftentimes we start examining a drug in patients where there aren't very many good treatment options. So, after many lines of treatment, for example and in that condition, you might imagine that because of the advancement of their disease and the number of treatments that they've received, they're already compromised, their immune system isn't working as well as it should be or could be. And in that setting, that's where the checkpoint inhibitors initially demonstrated some benefit.

But then as we move the checkpoint inhibitors earlier, where patients are less heavily treated or in this setting, in the adjuvant setting where we're treating microscopic disease, this is where the immune system really is still pretty functional for most patients, and we can harness that power with a checkpoint inhibitor. And I think what we're seeing is dramatic improvements in patient outcomes because we're using it earlier when the immune system is more active. And so, as you say, a lot of the hope of kind of changing a paradigm with regards to how we can treat these patients and improve survival, is coming to fruition, and we're seeing that this year's ASCO

Host: Your study in esophageal cancer, focused on patients getting chemotherapy, radiation and pembrolizumab, I believe before treatment, correct. Or before surgery. Can you tell us about that?

Dr. Shah: So, this was also one of the abstracts presented in the upper GI oral plenary session. And I mentioned just a minute ago that a standard treatment to treat esophageal cancer is with chemotherapy and radiation followed by surgery. We asked the question if we added the checkpoint inhibitor in combination with chemotherapy and radiation, would we get even a better benefit and the idea here is that maybe chemotherapy or the radiation can augment an immune response that the checkpoint inhibitor is trying to harness.

And we measured that by looking at the frequency of having major response in the pathologic specimen at the time of surgery. Historically about 30% of patients have a major pathologic response and our study, it not a large study is about 42 patients. But in that population, we found that the rate of a major pathologic response was nearly 49%. So, significantly larger than what we would have anticipated with just chemotherapy and radiation alone. It kind of highlights that checkpoint inhibition therapy could have activity even prior to surgery, which is a little bit earlier than Checkmate 577, where the treatment is given after surgery. The other thing that we found which there was some data about this in kind of retrospective analysis, looking at you know, patient charts and things like that. But we looked at it prospectively as part of our clinical trial. And we found that patients who had a major pathologic response had a much better survival, than patients that didn't have a major pathologic response.

And the reason why that's important is because, we might then be able to identify a group of patients that we need to do something more with or something different with. And I think that's an important aspect of drug development is want to help people we can help, but then the people that we aren't helping with the current treatments; we want to identify them early so we could try something novel. And I think this might be a very good marker for that. And then the last part about this study, which I think was novel was that we looked at very in-depth analysis to understand what was happening at the micro environment, the environment that the immune cells and the cancer cells live in.

And then we found that there were immune signatures that were associated with having a major path response or not. And I think this may open up new avenues of research as well. So, thanks for bringing that study up. I think this was an important study and we were glad to present it.

Host: Well, in a few minutes I'll come back to you about getting your take on a couple of new compounds that I think are very exciting and going after new targets. I want to take a second and just update the audience on a couple of practice changing studies in blood cancers. And ASCO tends to have at least numerically more of a focus on solid tumors, but there were some studies that I think are of interest to patients dealing with blood cancers.

Very briefly, the first is a randomized study comparing ibrutinib, which is one of the standard Bruton's tyrosine kinase inhibitors, a pill that affects a target that's very active in chronic lymphocytic leukemia, as well as other forms of B-cell malignancies. So, comparing ibrutinib, which is the first of those BTK inhibitors to acalabrutinib, which is a newer version that in some ways has less toxicity.

And this was in patients with recurrent chronic lymphocytic leukemia. The net of this study was that the efficacy is measured by progression-free survival of the disease was quite similar, but the tolerability or the side effect profile was much improved with the newer agent, the acalabrutinib in particular, there were fewer cardiac events. One of this side effects of this class of drug is atrial fibrillation, a heart rhythm abnormality. This was less common with acalabrutinib. There were also fewer bleeding side effects, which can occasionally occur due to these drugs effects on platelets, much as aspirin can affect platelets.

So, this I think is strong evidence that the newer versions of the BTK inhibitors are going to be for many patients, if not most, or almost all patients preferred drugs. In this case, acalabrutinib versus ibrutinib, the first generation of this type of therapy. There were also a number of other studies. I don't have time to go into the details. Trying to combine drugs with a BTK inhibitor in CLL, where the idea that by adding a drug such as venetoclax, which is an inhibitor of a protein called BCL2, that perhaps you can give a shorter duration of therapy. Typically, the BTK inhibitors are given indefinitely or long-term. The thinking is that if you combine them with other drugs, perhaps you can give it for a defined period of time. So, the patient does not need to stay on the drug quite as long. And we saw a number of studies exploring various approaches in that regard.

I'll also mention as some data in mantle cell lymphoma, a subtype of lymphoma. This was an inter group study of the National Cancer Institutes Cooperative Groups led by the ECOG or Eastern Cooperative Oncology Groups. But the other groups participated in this study looking at bendamustine plus rituximab as a standard therapy in combination with a few other agents in mantle cell lymphoma suggesting that the BR based therapy, which was commonly used in practice has a progression-free survival of over five years. So, that is a pretty respectable, not perfect, obviously, but pretty respectable outcome for an outpatient treatment in mantle cell lymphoma.

And then also in mantle cell lymphoma our colleague, Peter Martin at Weill Cornell presented what we call real-world data, looking at over 3,400 patients treated across the country in the US in practice with mantle cell lymphoma. And the interesting findings of this were that relatively few patients receive intensive treatments out in the community and in the real world for mantle cell lymphoma, whereas at academic centers, Mantle cell patients often are treated with very intense approaches.

So, it really highlights the idea, and I know Manish that you have seen these in other areas, the concept of real-world data being of interest in importance that while we see these and participate in these clinical trials, that in the real world and practice patients may be different, physicians may have different levels of comfort and what's done in the community may be very different. And that's, I think for many patients, a reason to consider getting a second opinion or additional input into one's case, if that's feasible from a specialist in a particular area that might be able to offer additional options for a patient.

And then finally, I'm just going to mention one highlight from the Alliance for Clinical Trials and Oncology in classical Hodgkin lymphoma, which is a curable type of lymphoma, typically treated with chemotherapy. This was a single arm study of patients with bulky disease and large masses, in particular, 10 centimeters or greater occasionally occurs in Hodgkin lymphoma. This is a less favorable outcome typically and is often treated with radiation therapy, which can be effective, but has side effects, particularly in young women who have risk of breast cancer if they're getting radiation to their chest, And so this study looked at omitting radiation treatment in a subset of patients who had negative PET scans partway through their treatment and suggest that you can delete or leave out the radiation in that group of patients, which is a very important and useful finding to avoid potentially long-term toxicity.

So, in a nutshell, those are some of the heme malignancy highlights of ASCO this year. And Manish, I want to turn back to you for our last couple of minutes and just ask you about two novel compounds. The first of which targets something called KRAS, which is important in cancer. It has been a challenging target for many years, but we now have a drug that goes after KRAS in a subset of patients with lung cancer. So, what is KRAS and what is this new development and its impact for patients?

Dr. Shah: So, KRAS is a protein that's involved in the pathway that leads to cell survival. And it addresses sort of how cells take in sugars and metabolize food and things like that. And about half of cancer cells have some type of a mutation in KRAS and there are many different types of KRAS mutations. And it's important because it's been a known target that was actually what we thought of as undruggable, that there wasn't a way to identify a new drug or molecule that could actually attack cells that had a KRAS mutation and that, you know, that's been the mainstay of cancer treatment for decades is to identify a target and then make a drug that hits that target.

But we couldn't do that for KRAS up until recently. And so, as you mentioned in lung cancer there's this specific type of KRAS mutation called the KRAS G-12-C mutant lung cancer. This is about 12 or 13% of all lung cancers. And there's a new drug called sotorasib which targets specifically the KRAS G-12-C mutation.

And in the code break, 100 study that was presented in the long session this weekend, we found that the sotorasib molecule actually led to a response rate of about 37%. So about a third of patients? with a KRAS G-12-C mutation, they actually had a major response in their tumor with this new molecule, which is really quite exciting and likely to be practice changing.

4% of the patients actually had a complete response, meaning all of the disease that we could identify by radiographic imaging had disappeared with the treatment. So, it was a smaller study, but is something to be aware of that new drugs and new targets and particularly targets that were previously thought to be undruggable are now becoming druggable with modern techniques. So, that's really quite exciting for oncology.

Host: And then finally briefly there was a new drug that targets something called NRG1 fusions and that's particularly applicable to pancreatic cancer. Can you briefly tell us a little bit about that agent?

Dr. Shah: So, we were talking about KRAS mutation. So, pancreatic cancers, 95% of patients have a KRAS mutation. It's a different one than I just mentioned in lung cancer. So, amongst the 5% of patients that don't have a KRAS mutation they tend to have a fusion in NRG1. NRG1 is also known as neuregulin. And it actually binds to HER2 and HER3 and stimulates the same pathways that the KRAS protein would stimulate in terms of managing sugar metabolism and cell survival and promoting growth and tumors that have this NRG1 fusion are activated by this pathway. So, this new drug, inotuzumab specifically targets this NRG1 fusion, and they found that in pancreas cancer, so again, this is a small portion of pancreatic cancer. It's a fraction of the 5% that doesn't have a KRAS mutation. But as you know, pancreatic cancer is one of the hardest diseases that we can treat. And in this population, it was 12 patients that had an NRG 1 fusion amplification, the response rate with inotuzumab was 42%.

And in fact, only one of the 12 patients didn't respond at all. The other patients that didn't have a major response had at least stable disease. So, it really suggests, again, that it's a new target and in a small population, but if you identify the target that actually drives the tumor and you can hit that target with a drug, you can have a major impact. And so I think that's one of the reasons I thought we should highlight this compound.

Host: I think it's a theme as you mentioned that we're getting smaller and smaller disease populations, but more targeted therapies. And so, hopefully that identification of such will be helpful and that we can really zero in on the right drug for the right patient. As we finish up, I just want to ask you about one other area that gets a lot of attention.

We've been looking at it in hematologic malignancies, and it's particularly relevant in lymphoma and relapse risk and that's the concept of circulating tumor DNA or CT DNA. How do you see that evolving and any new highlights from ASCO that you think are worth mentioning?

Dr. Shah: So, this is another very exciting area of research. So, I think a theme that as you point out is sort of better identifying patients who you know, might be vulnerable for a specific target. The circuiting tumor DNA is a way to identify patients that have a very small volume of disease. These are patients that typically the CAT scans or PET scans don't show that there is cancer, but we can identify very small amounts of DNA that come from the cancer in the blood. And we're just now learning about how to use that to our advantage. So, for example, in colon cancer there's an ongoing clinical trial where patients who after receiving adjuvant therapy, if they still have some circulating tumor DNA, there may be benefit to switching therapy to try to eradicate that disease.

And conceptually, you might imagine, you know, the impact of this. So, if you can eradicate the circulating tumor DNA, you may be able to prevent the recurrence. And that actually gets to what we were talking about much earlier. It's not that we're delaying the disease from coming back, we're preventing it from coming back and that has a dramatic impact on survival.

So, I think this is the impact that we could have with CT DNA and other types of tests to look for minimal residual disease. One of the things that we're doing here, but across the country as well, not only looking at circulating tumor DNA, but also looking at circulating cancer cells or CTCs and the advantage of that might be that you might be able to identify specific clones that have unique properties that you could target, as opposed to just identifying the tumor DNA.

Host: So, our time is coming to an end. It seems like there's lots of reason for optimism. And I think all of the studies that we've highlighted, really emphasize the value of participating in clinical trials and research studies where these things are being developed and patients can have the first access to them. Any other takeaways you want to share with our audience before we finish?

Dr. Shah: It's been a pleasure to be with you on this podcast. I think I say this every year, but this year was a truly a banner year for positive studies across solid tumor malignancies. I think that we're demonstrating that we are advancing the field and improving patient lives with novel targeted therapies, better selection of treatments specific to tumor mutations. And as you point out, I think it highlights for us that we really, you know, none of these advancements would be possible without the research process and participating in clinical trials, activating them and studying different aspects of drug development. This is the way that we make improvements.

Host: Well, thanks for all your work in this area. And thank you very much for sharing your expertise with us today. I want to invite our audience to download subscribe, rate, and review CancerCast on Apple podcasts. Google podcasts, Spotify. We're online at weillcornell.org. We also encourage you to write to us at cancercastatmeddotcornell.edu with questions, comments, and topics you'd like to see us cover more in-depth in the future. That's it for CancerCast; conversations about new developments in medicine, cancer care and research. I'm Dr. John Leonard. Thanks for tuning in.