 Okay. Thank you, Dr. Gore. That was excellent and good. We're a couple minutes behind, but I'd rather stop for questions and get people's involvement and we can fudge a little bit on our break times and catch back up. I don't have any video display in mind, so John set the bar high. I should have put you at the end of the day, John. Oops, that's no good. I can lug in myself. We need our AV help. Yeah, it is. Oh, okay. Good, good. If we're all set. So I want to talk for a session today about adjuvant therapy for kidney cancer. So what does that term adjuvant mean in cancer therapy? So adjuvant therapy is additional treatment that would be given after primary therapy applied, usually for most cancers implying definitive surgical treatments. So you've taken out a tumor surgically. You're leaving the patient without any identifiable measurable disease. And you know historically, depending on the characteristics of the tumor, the staging that's applied to the tumor, usually you have that data after the surgery is complete. You know that there's a risk for future recurrence and the stage distinction is how much risk. And so the questioner then arises, well, can you change that risk? Can you apply a therapy after you recover from surgery that's going to decrease the risk of a future disease recurrence? And typically we're thinking about primary surgical therapy and just as Dr. Gore was speaking about, for kidney cancer, surgery on the kidney, taking out the primary tumor. And for adjuvant therapy, usually we're thinking about modalities like radiation therapy or medical therapy. So as a medical oncologist, primarily thinking about what medicines could be applied that would change your future risk of disease recurrence for kidney cancer. So going back to a slide I showed you at the outset that for kidney cancer diagnoses, the majority of patients, the solid majority, have a localized disease. And so most patients are going to undergo an refractomy surgery offered as potentially curative therapy for their cancer. So this is going to come up with regularity patients. They're now post-surgery and wanting to know what should come next. If you look at what's the hazard of recurrence of kidney cancer, this is data from a large national database called SEER. So in all commerce across the board, not thinking about the stage distinction, five-year survival rate for kidney cancer is 74%. That's not such a helpful number because we're always going to tease things out in terms of what's your stage of diagnosis. In this data set, they didn't use the stage one, two, three, four distinctions, but local, regional, or distance spread. And so local kidney cancer is basically going to be stage one or stage two tumors. They're only in the kidney. They're not impinging on some of the associated structures like blood vessels and lymph nodes. And the disease control with surgery is excellent. So five years greater than 90% survival in this data set. Regional kidney cancer implies, again, a localized disease process. It's only in the kidney, but now there's something about it that increases the risk of future recurrence. It's beginning to follow the blood vessels. It's in the renal vein. It's growing through the kidney tissue proper. It's into the fat around the kidney. It's showing up in lymph nodes associated with the kidney. So the surgeon is still completely removed the tumor. But now you're looking at typically a stage three kidney cancer diagnosis. And in five years risk of recurrence is about 35 to 40%. There are later recurrences. I generally quote patients about a 50-50 lifetime risk of recurrence with stage three kidney cancer. And then distance disease means the time of diagnosis, you have metastatic disease. And in that setting, in a fairly contemporary cohort, five years survival only 12%. So that falls into the realm of treating metastatic disease, which isn't the primary focus of this talk. But depending on your risk for patients that are considered to have high risk localized kidney cancer, it's a very valid question. Could you not apply a therapy that's going to change that risk? Decrease the risk and save lives because a subset of patients won't have their cancer come back because you apply an effective therapy. There are some terms commonly used in research studies that are slightly different. And so I thought it was worth just going through for a moment. What is meant by disease free survival if you're looking at a study versus overall survival? So disease free survival at any time point after the study begins, a patient that's had surgery, the cancer is removed. And so post-operatively there's no evidence of cancer. And now you start the clock and you watch that patient moving forward in time. What percent of your population of patients remain without any cancer findings? So you've failed, you're no longer in the disease free group if your cancer comes back. Doesn't mean that you're dead. You can be living and treating the recurrent cancer. But as far as the cancer comes back, you're no longer in the disease free population. It's faster to measure disease free survival than overall survival because as patients have recurrence of their cancer, maybe they can have surgery, maybe they're going to get medical therapy. There can be a very long time interval from detecting disease recurrence before that cancer may progress and the patient actually dies of that cancer. And then becomes an overall survival data point. But the problem is, what if you apply therapy that delays the time to cancer recurrence, which seems like a good thing, but doesn't ultimately prevent the cancer from coming back? So if you wait long enough, everyone destined to have their cancer recur, it ultimately all recurs. And is that really getting you anywhere? Have you gained anything? Because maybe the progressing disease, when it grows back and it's been treated with the medical therapy, is now different. It's more aggressive, it's harder to treat. It's intrinsically resistant to the therapy you applied to try and stop the cancer regrowth. And so maybe you do worse treating that cancer when you can see it on scans and you follow it. So at the end of the day, maybe you really haven't gotten anywhere at all and the natural history of the disease is playing itself out and you really haven't changed anything. And so that is the concern when you look at disease free survival. Is that faithfully giving you insight that you've gained an overall survival? So we prefer to know about overall survival, which is that at any time point, who's alive and who's died. Now death can be from any cause. You're giving up the fact that it's closely linked to the cancer. But it's short time intervals after a cancer diagnosis, one year, two years, three years, even five years, the hazard to the patient is far and away greater for the cancer than for other processes. And if you're doing a randomized study, risk of death from other medical conditions should be balanced between groups. So that generally doesn't come into play as being a major concern. And it's really for an adjuvant therapy, the gold standard applied for most diseases is you want better overall survival if you're truly going to believe that a therapy should be applied and you're really gaining value for the patient. So just one slide on radiation therapy following nephrectomy. It's an issue that has been looked at, although the data sets are not terribly contemporary. Older data, 80s, 1990s, there are two randomized studies and then there's a larger meta-analysis that I think most people kind of refer to as being the definitive statement. The two randomized trials pooled with other studies that were retrospective in nature, 735 patients. And the question is if you apply radiation on recovery from nephrectomy to the surgery bed to come out ahead, do you prevent disease recurrence? The answer is no. There's no clear survival signal. You're not gaining disease control that rises to better survival. And so generally that's not offered and not done as a routine therapy. So thinking about medical therapy and drug development, the drugs that we have available for kidney cancer and applying those in the adjuvant setting, and we're going to look at where we stand with different types of drug therapy. But as you think about the development of a drug for cancer of any kind, including kidney cancer, it has a very stereotypical progression of how the drugs are evaluated. So typically the first time you try a brand new therapy that has a scientific rationale, it seems like a smart thing to do for a certain cancer, but to prove the point that it actually has value and it can treat the cancer, usually you're going to do a first study in patients that have more or less exhausted good therapies for their cancer. You don't know what you're getting into. You don't know the risk. You don't know if it's going to work. And so patients typically are required to have failed at least one or sometimes multiple prior therapies. And for diseases where there are curative therapies, usually the language of a very first study would require you've exhausted all modalities that might cure your cancer. So ethically you really need to be, and unfortunately a bad spot for what's on the table for standard cancer therapy to make it worthwhile to embark on something that's quite investigational. For a drug that looks promising, it works well. Maybe it goes all the way forward and gets approved as a second or third line therapy for a cancer. If it looks quite compelling, then the question is, well, is this actually the best available therapy for this cancer? And should you start off with this drug and use it right off the bat because it's the most potent drug? Treatments that typically begin at the back end of a list of therapies for cancer then come up and get looked at as perhaps the primary therapy and usually in a comparative fashion. Is the new drug better than what's the current standard? Head-to-head comparison study typically large, what are called phase three trials. And so drugs that prove to be potent in that setting will almost always then be looked at in a preventative or the adjuvant setting. So here's a drug that works very well for our cancer. If we've discovered it, we've proven it has value. In fact, it's the most potent drug we have for this cancer. Can it actually work in the preventative setting in patients that have had local therapy and now we're fearful the cancer is going to come back? So that's the general progression, which means the timeline of getting around to the adjuvant questions, usually at the end of the list of doing several studies with drugs. And so it's not usually the first question and drugs that are newly available. Typically you don't know yet what's their role in the adjuvant setting. This is a little schematic that just gives you a broad overview of the drugs that have become available for kidney cancer and how the treatments have changed in their nature in the way they attack the cancer. So if you go back before the mid-1980s, there really was no standard therapy for kidney cancer. It wasn't for lack of trying. There are dozens and dozens of studies of all sorts of chemotherapy agents, hormonal agents, that were very, very ineffective and generally not helpful. In the late 1980s, interferon alpha became available as a therapeutic agent, followed shortly thereafter by interleukin 2. And so those two drugs were called cytokines. They're recombinant versions of hormones your body makes in response to immune stimuli. Worked well enough that they showed benefit and they got FDA approved for treating kidney cancer. And that was standard therapy for a very long time, from early 1990s until 2005. And so we had an era of cytokine therapy for kidney cancer. The world changed in 2005 with the first approval of an oral targeted therapy. Seraphanib was the first drug in class, but rapidly followed by several other drugs that were very similar and in fact mostly replaced by the other drugs that appeared to be incrementally better. So targeted therapy, which right now is front and center and most patients are receiving these drugs and often multiple of these agents in the same drug family. So the era of targeted therapy. And then the world changed again in 2015. So November 2015, the FDA approval of Nevolumab, first in class of what are called immune checkpoint blocking antibodies, the only one so far approved for kidney cancer, but there's several other commercially available similar drugs for other diseases. So an immunotherapy compound, attacking the cancer in a different way, and that's the immunotherapy class of drugs is really dominating clinical developments and research studies in the last several years. So where do these drugs stand in terms of adjuvant therapies? The old cytokine drugs have been looked at and then were tested in well-designed clinical studies looking to see if they have a role in being preventative therapies for kidney cancer. So I show you a couple of these studies listed out that comes from a research paper that shows what's called a force plot, so sort of a tree-like structure, showing you the relative hazard ratio and the statistical variance of those hazard ratios. What that means is what's the relative effect of the treatment arm versus the observation arm. So absolutely no difference. The survival you measure is exactly the same, would be 1.00. A smaller number would imply the interferon treatment did better or the lotus interleukin-tuplis interferon. A number greater than one implies that observation action was better than the therapy applied. And then if the variance around the measured value crosses 1.0, it's judged that these differences are not statistically meaningful. And so there's three independent studies and then they were analyzed in meta-analysis, meaning pooling these results. So 840 patients getting cytokine therapy. And there's a slight increase above 1.0, but a confidence interval that overlaps 1.0. So the interpretation is no meaningful difference between applying cytokine therapy versus doing nothing at all and just watching patients. So not a helpful intervention. Interleukin-tu, back in its day, when it was the only drug available or the only drug with interferon, was experimented in all sorts of regimens and doses. There were low dose regimens that were outpatient administration, very well tolerated. There's a high dose regimen. Some of you in this room may have received far more toxic and unpleasant requires an inpatient hospital stay. That approach, the high dose approach with IL-2 has been tested is in a prophylactic way in a fairly small study, but no positive benefit in patients. And that approach has not been revisited. Certainly not a therapy for everybody would be a selected subset of patients. But no hint that that's moving in the right direction. So the cytokines have been looked at in that context and really abandoned as being a useful modality. What's front and center and data that's beginning to emerge from large clinical studies that take many, many years to organize, to enroll patients and then to wait and see as the data emerges what you've learned. So in one slide really presenting an impossibly large amount of work, hundreds of cancer cells hundreds of cancer centers and data collection spanning a decade or more. So it's really a tremendous amount of efforts. Six studies that have looked at the issue that the new generation of targeted therapies have a prophylactic role in managing high-risk kidney cancer. So the first study of the Assure trial 2006 and the last study of a similar kind the ATLAS study that began in 2012. All studies I believe have enrolled all the patients that they intended and they're all now just tracking the outcomes of those patients. And three of the six have reported results and the most recent I'm going to spend a few minutes on what's called the PROTECT trial was a study that we participated here at SCCA a randomized study where patients either got the drug pisoponib also called votrient or were receiving a placebo. All of these trials except for one of the study drug. And so very very similar structure you're getting a pill you don't know for sure if it's the real medicine you're taking it for a year and then you're being followed by a surveillance calendar very reminiscent of what Dr. Gore talked about that would be consistent with treatment guidelines to see what happens to the two different patient groups. The last trial here the ATLAS trial is going to treat patients for three years with the ACSITNib so a little bit of insight the company that makes ACSITNib own SNITNib and undoubtedly had insight that the one year of SNITNib was proving to be unhelpful and so they decided to do a different experiment and go longer. So we'll see if that's meaningful. But let's just take a look at some of the results this was the ASCO meeting in Chicago June 2017 first public release of results with pisoponib and one figure I particularly liked that I think gives you a graphic impression of what are we asking of you as the patient these medicines are not innocent drugs they come with side effects people don't feel well and this is a quality of life questionnaire patients filled out over the timeline of the PROTECT trial so the placebo patients that were taking nothing just a fake pill are the yellow line here and so they felt normal they felt fine and the score value 0.0 that's your baseline patients taking the true drug pisoponib they felt lousy for a full year on therapy but as therapy ends the side effects go away and they go back to feeling fine but this drop off in quality of life that's given a quantitative metric that's arbitrary I just think that's a lovely graphic representation that it's not a free ride you're taking a year worth of drug that's making you feel lousy for years kind of a long time that's a lot of effort and work and bother and so what is the gain well the gain is so far absolutely nothing at all unfortunately when you look at the survival curves of the two treatments placebo or pisoponib they're almost completely overlapping and there's no statistical difference between these curves so the gold standard test the overall survival benefit of this drug was absolutely nothing the disease free survival which was also captured and measured also was judged to be statistically not different and so unfortunately a negative study not showing benefit for pisoponib and to summarize so yes good question you had to have localized disease and high enough risk to judge it to be worthwhile and so I didn't print out the enrollment eligibility for most of these trials all stage 3 patients were eligible for many of the trials you could be stage 2 but then you had to have other features the nuclear grading scale on your pathology report had to be a high grade tumor usually grade 3 or grade 4 from stage 2 and then any stage 3 is the usual cut points by and large for the different studies so if you look at the three different large trials that have now been presented in terms of outcomes the assured trial actually had three different treatment arms it had a suenitinib which is suetent it had seraphonib, nexivar those were given as separate independent therapies not given together and then placebo so three different treatment groups in that study very very large study, 1900 patients and there was no disease free benefit and no survival benefit so completely negative experience delivering those drugs for one year therapy first reports with this approach very very disappointing for the field I must say people were very optimistic with this approach before the data began to be released last fall the S-track study presented its results and curiously it's a second study with suetent and that did show statistical benefit of disease free survival but so far overall survival shows no difference and so that's the odd dichotomy are you just delaying the inevitable and are you really getting anywhere so I think most people in the field will hold the study to showing a survival benefit before there would be moved to think that you should be recommending suetent for patients but it's very puzzling that the same clinical experiment was done twice and came to a different conclusion and in all honesty there's really no explanation for that people have sort of hemmed and hawed over what was done differently and wasn't meaningful but you know there just isn't an explanation and then the protect trial brand new data from a month ago negative for disease free survival negative overall survival so I think in the bulk of evidence three different experiments, different drugs similar approach, year therapy and it doesn't seem like we're getting anywhere as adjuvant treatment so we certainly have not adopted trying to use any of these drugs in the adjuvant setting a standard of care none of them are FDA approved to be used in that fashion either so you couldn't easily write a prescription for patients even if you wanted to go that route so if we go back to our schematic here so we've crossed cytokines off the list as not being helpful we're right in the thick of learning about the utility of the targeted therapies there's still trials that haven't been complete but we're becoming quite pessimistic that you'd think if any of these drugs work they probably all would work and so a couple of negative trials have really poisoned the field and I think at this point nobody's really expecting that the pending trials are likely to be dramatically positive so what's coming next what's coming next is taking the new class of drugs the immunotherapy drugs and doing the same experiment and seeing what happens there so just a quicky cartoon about what do we think we're doing what's the biology of the new generation immunotherapy drugs starting down here on the left we know that tumors are abnormal cells many of the cells within a tumor mass are dying even though the tumor is growing larger so it's creating material that's picked up by the immune system which is the scavenger system getting rid of dead cells and there are immune cells whose job it is is to show the immune system material that's being chewed up and metabolized to make sure there's nothing there that's abnormal and so the important cell in your immune system that can actually detect an abnormal cell like a tumor cell and turn on and react to it is called the T lymphocyte or T cell so that's central to the biology of what we think is happening spontaneously but just not happening and working to a vigorous degree that's curing the cancer when T cells turn on they turn on a whole organized program of gene expression they become activated where they can recognize and kill off a target which is good but they turn on a mechanism to shut the whole system down so it doesn't go crazy and damage normal tissues and so as T cells activate and go out and find targets they begin to express proteins that can shut them off and one of those is called the PD1 protein that's on activated T cells so T cells that are inside of tumor tissue and crawling around and hopefully giving you an anti-tumor effect can encounter the binding partner for PD1 called the protein PDL1 PDL1 can be made by the tumor itself so the tumor shields itself it defends itself by making a protein that can turn off immune cells right at the point of action where the T cell is bumping up against tumor cells and so blocking this interaction on either side of the equation either blocking the PD1 protein or blocking the PDL1 protein represents this family of what are called immune checkpoint drugs and they're proving to be widely effective across numerous different tumors and becoming some of the most widely used drugs across cancer in general and can work quite well in some kidney cancer patients so what's coming and is going to be looked at now in the next few years is applying these drugs in the adjuvant setting in large studies several hundred patients and trying to prove to point that these drugs do or don't have a prophylactic role in the setting of kidney cancer there's a similar drug that's not listed here a drug called Urvoi or Ipilimumab that's FDA approved for melanoma that has had a positive adjuvant study in melanoma patients so that's definitely encouraging people to think that this drug class may be unique and different and better than the other types of drugs that have been tested and will actually show us a true benefit in this setting but it's going to take several years to collect and then wait and analyze the data there's four studies that are all overlapping each other and open and rolling at the same time the emotion trial is using the drug Etizelizumab the prosper trial a drug called Nevolumab which is an FDA approved drug for kidney cancer the keynote study using Pembalizumab or you may know that as Ketruda and then the checkmate trial is combining Nevolumab with Ipilimumab or Urvoi so a two drug cocktail the only study that's combining more than one drug in this setting it wouldn't make sense for a single cancer center to have all these studies open because they're redundant they're recruiting the same patients high risk patients high risk stage two and stage three patients with kidney cancer so at our center we have the good fortune of choosing amongst these and are going to open the keynote trial that's Ketruda or Pembalizumab trial that's in process should be opening later in 2017 and so anticipating that study will take anywhere from one to two years to enroll patients we'll have a chunk of time where we'll have the opportunity for patients to participate in this study to maybe get a prophylactic immunotherapy drug recognizing it's randomized and blinded so 50-50 chance you're getting the true drug versus just saline placebo infusion so you have to be okay with that scenario so where do we stand for adjuvant therapy you know there could have been one slide with the big red slash there is no FDA approved proven effective adjuvant therapy for kidney cancer despite lots of well done large studies trying to identify an effective approach so standard of care at this day and age continues to remain ongoing surveillance for patients with no recommended active therapy there are pending studies that are complete and we're just waiting for the data to mature with targeted therapies so there's the chance that one of these drugs will show a benefit and actually come into the field as a possible therapy for patients but so far results are disappointing and so fields getting fairly pessimistic that it's going to bear fruit with targeted therapy and then the immunotherapy trials are just getting up and going so it's going to be several years before we have an answer but that'll be something that's at least available and ready in prime time for patients question so yes nothing unfortunately is risk free you know although we like immunotherapy drugs for our patients and think they're sort of quote well tolerated there is a side effect profile 10 to 12% of patients in the metastatic setting will be forced to stop therapy for so called intolerable side effects there's even the risk of side effects escalating to being a cause of death in upwards of 1 or 2% of patients in the metastatic treatments patients that have metastatic cancer are motivated to do something about their cancer and they're willing to assume a greater risk it's an awful experience to take somebody that is completely healthy has negative scans for cancer put them on a therapy that makes them severely ill or they even die from the attempt to treat their cancer and prevent that because you don't know if they're destined to have their cancer come back so it's a whole different world where your tolerance for risk and toxicity is quite different in an otherwise healthy cancer free group of patients at least at the outset of therapy when it comes into play about this panel of studies there's not a huge amount of difference between the different drugs but perhaps some slight differences but the one approach where you're combining two drugs together clearly increases your chance for bad side effects and so that myself and my colleagues looking at our opportunities was something we discussed and we're fearful about based on our experience with our melanoma patients our convoy therapy for melanoma is given at an unconventional high dose and the side effect profile is fairly extreme and we have had patients that came into that treatment completely healthy and had really terrible problems and that's again that's a very awful situation so we'd like to think Pembrolizumabg only goes pretty smooth but there definitely will be a subset of patients where it causes some pretty unpleasant side effects hopefully not arising to the level of patients actually dying statistically most patients are likely to have mild or no side effects but again it's not risk free question here so the data for that approval came largely from a trial called the checkmate 025 study so randomized phase 3 trial in Pembrolizumabg was compared to an approved drug called Affinitor or Everlymus head to head 50-50 and was the better drug for the antitumor effects was actually the better drug for patient preference and side effects as well so that was most of the data this company bundled smaller precursor studies as well into their filing with the FDA that study probably took about three years to complete I think the timeline of the immunotherapy drugs was really brief the movement through advanced clinical testing was very rapid in part for the enthusiasm with these drugs and in parts for the competition from other companies that had similar drugs and knowing that they were clearly effective and were going to be winners and get through the FDA there was a lot of intense pressure to try and beat the next guy and get your study done so it went very quickly the average timeline from a new drug being tested in the clinic for eight to ten years the FDA has tried to accelerate that and so something more like five to six years in contemporary time is probably more typical so a three to three and a half year timeline is actually really quite short so these studies are all for localized kidney cancer so some stage two and stage three patients trying to be preventative therapy Nivolumab is approved for advanced for stage four kidney cancer and now it says you had to have had a prior therapy that's no longer working like Siu-Tent or Votrient there are studies that have been completed but haven't been reported where Nivolumab has given us primary therapy first therapy for kidney cancer if those studies are positive then it will change its FDA guidance and you'll be able to prescribe it as the initial therapy for patients so that's pending data the word on the street is maybe as early as late 2017 as it was presented publicly and that may change the use of Nivolumab so once the drug is FDA approved as being prescribed to patients there's no active data collection so the broader experience isn't being actively measured and quantified there are mechanisms where physicians can report to the FDA particularly bad or unusual side effects so the FDA does have a reporting mechanism where the FDA physicians get these letters soliciting data entry and data collection for patients that report side effects I believe to the dispensing pharmacy you get a call and if you tell the pharmacy contact that you've had certain side effects that they send off a note to the FDA that triggers a mailing to the prescribing physician trying to collect that data trying to get real world side effect experience that's an obligation for the doctor to actually send that data in I can just throw that in the trash and ignore it so it's highly imperfect question in the back so right for any doctor prescribing a treatment as a standard therapy because of FDA approval what happens to you is not actively collected unless you're participating in a study so for example the company that owns Nivolumab that we participated in that included patients that weren't part of the study that gained FDA approval so that study only allowed for example clear cell histology as your diagnosis they did an add on study and they allowed any kidney cancer diagnosis so papillary kidney cancers, chromophobic kidney cancers could receive the drug even though the FDA doesn't restrict the use to clear cell so you could have prescribed it for a patient but in a study then you know the data is being collected and it'll be analyzed and you'll learn something about patients that weren't part of the patient experience that was the data leading up to FDA approval but you have to be formally enrolled in a study to have the data collected and actually analyzed for most people it's simply standard of care therapy and it's not something that's being collected so yes, so most studies there's active therapy but if that active therapy ends you'll know what happens to patients for disease status new scans overall survival unless the study closes down and simply says okay we're done that's all the data we're going to collect or a lot of times you'll be monitored unless you start on some alternate cancer therapy and then at that point in time you leave the study for any ongoing assessment because they assume now that's going to muddy the waters it's hard to judge what their drug has accomplished because now you're receiving some other treatment for a study you're monitored if you're not doing any active therapy you're part of the study but then if you receive a next treatment then you leave the study formally at that point but ongoing outcome for overall survival as a long long tail for research studies is very common question in the back so I mean a good portal is your doctor but you know most community physicians do clinical trials so they may or may not be very aggressive in helping you find stuff there is an excellent web portal this clinicaltrials.gov is the most comprehensive listing site for clinical trials of all kind it is kind of daunting if you search for something and you get 50 or 100 or 500 clinical trials that populate a list that you pull up how do you weed that down to things that are actually relevant but that might be an area where you could meet with your doctor and help sort through things that you're interested in or things that you've found you know a cancer center like ours where a big part of our mission and our goal is to participate in research ideally we're going to know we're going to have things here but if we don't have it we could tell you in a fairly educated way what might be available to you in the greater northwest in the cards that you travel to some fairly far-off cancer center research trials are always linked to the participating center and so if you went for an opinion at MD Anderson or Sloan Kettering or Cleveland Clinic and they had a trial that sounded really exciting you usually can't export that and come back home and be in the study and be here in Seattle you have to work with that cancer center as you're treating doctors the doctors analyzing your scans you have to either commute or live in that city and so for most people that's not really in the cards but for a few folks you have friends, you have family you can actually come and go to Houston or some city that has a cancer center that's doing something that's interesting to you it might be feasible but that's an unfortunate feature of the clinical trial process question here so that study is for metastatic disease so first line therapy for patients with stage 4 disease this is all for patients with localized kidney cancer so stage 2 or stage 3 so different subset of patients if I can just mix a number of drugs together hopefully that I'll find the right combination to come out do you see the artificial intelligence and machine learning to like take some of these trials and quickly get to the bottom of whether there would be a positive outcome and with the question in the back also I was doing some research and it turns out that usually about studies that come out for a week or more than the research center can digest so some research centers are using IBM Watson to get a more global view of this is the 10,000 trials that happen this week so people have access to all the insurmountable amount of information that needs to be digested and at point to different possibilities for their individual treatments well you touch on a number of issues the idea of how can you quickly figure out what might be the best therapy comes into play so with the immunotherapy drugs that are available there's a zillion similar drugs related drugs other immune stimulating drugs and so right now the field is fascinated with combinations give one of these drugs plus something else and how can you quickly figure out which ones are fruitful which ones are not going anywhere and what is called TASC the company that owns Nevolumab has piloted what they perceive to be a strategy to rapidly work through a whole series of two drug combinations in a more efficient way than the usual mechanism called the fraction protocols for different diseases we'll see how that works out on the one hand investigators that are specialists unlimited number of drugs that have enough data that you know they're clearly working and so having a feel for what should be looked at in a definitive large study I don't think is something that you can't sort out fairly easily but what you touch on is the universe of all possible clinical trials is immense every time I go on clinicaltrials.gov and search for something that I know about I hit on all of these studies that I never even knew existed that I look at them and I'm like oh that's pretty cool but we'd like to have that so it is there is this massive world of studies and anyone cancer center can't possibly participate or even really know in completion what's out there and available but you know pragmatics are that you'd have to travel and go to different cancer centers all over the country if you want to participate in these different studies I mean there is what's available in your own backyard but then there's this massive world of other things you might be interested in so for the person that they're not limited you know and travel in time and could actually truly search the entire country for an interesting study that is a very daunting task and even your local oncologist probably isn't completely up on every last thing you could find in a web portal like this and that's I don't have a perfect answer for that there are commercial clinical search services that will help you identify relevant studies and help contact centers find out if they're actually open and rolling I have had a few patients bring in lists provided by services to help them try to identify studies so that might be something useful but most people are limited by the reality that if they saw things in other places it's not feasible yeah this can be something that you invent so we'll see you in Shark Tank spinning your idea I mean it is it's a great topic I don't have a perfect answer so for any study you participate in if you're actively working with us and we know results have been published we try to tell you that you know there's public announcement of your study and what things look like I don't think the study mechanism itself necessarily contacts you and like would send you a participant letter announcing that you know here's the results of your trial they've just been published I think it's kind of on the doctor to tell you well yes the goal of these studies is to identify an effective therapy that then gains FDA approval that everyone can use it and prescribe it so every oncologist should be on guard for new definitive studies that are going to change practice and new FDA approvals so they can change the care for their patients and so that should be something that any good oncologist is aware of but actually participating in a research study you know in advance the study is coming and maybe you're even involved in it as the participant versus the day that there's the FDA announcement of an approval you know people already expecting that and know that and know the study was complete and results were discussed so that's kind of late in the game that shouldn't be brand new shocking news to anybody when that announcement finally comes along that just opens the door that you can now prescribe it and insurance will pay for it so we're a couple minutes behind our target why don't we take ten minutes eleven oh five we'll come back and jump into the next two sessions before the lunch break