 I'm Bill Brough and this is Kidney Cancer News. As we span the globe with stories of interest of families dealing with kidney cancer as well as medical professionals, this month we'll hear from Dr. Tim Eisen, one of the presenters at our most recent kidney cancer symposium in Chicago. We'll also take a look at the latest issue of kidney cancer journal and we have news of an important development in vaccine research, too. This month's edition of our print publication, Kidney Cancer Journal, Volume 10, No. 2 for 2012, features an important article on locally recurrent renal cancer, update on surgical interventions and prognosis. The late father of a deceased patient sponsored the work of the International Kidney Cancer Working Group, funded by the Kidney Cancer Association. This is a project that was in process for more than a decade. And a paper has been published in the Journal of Urology, improvement in overall survival of patients with advanced renal cell carcinoma, prognostic factor trend analysis from an international data set of clinical trials. You can read an abstract of this paper online at kidneycancer.org. IMADIX Biotechnologies, a biopharmaceutical company developing a rationally designed therapeutic vaccine active against cancer, has announced that it has completed patient recruitment to the Pivotal Phase III trial, evaluating its lead cancer vaccine IMA-901 for renal cell carcinoma. The trial has completed patient inclusion. It's expected that around 345 patients will be randomized across 10 countries in the U.S. and Europe. The first overall survival results are expected during the first half of 2014. For complete details on these and other stories, point your web browser to kidneycancer.org. Look for the pressroom link on the homepage. Now Dr. Tim Eisen kicks off the first in a series of reports from the recent International Kidney Cancer Symposium in Chicago. Both of you can view both presentations and abstracts from this meeting online at kidneycancersymposium.com. Sure, it's a pleasure. Thank you very much for asking me to do this. I'm a medical oncologist and I work in Cambridge where I'm the professor of medical oncology and I specialize in kidney cancer and lung cancer there and I also help run the clinical research side of our operation in Cambridge. So I've been working in kidney cancer now for several decades, two decades, and so I was involved with the initial developments, particularly of seraphonib and then some of the other drugs involved. Yes, I'm presenting a summary if you like and my view of the data that will affect the choice of first line treatment recommendations for patients. So I think there are a number of things that I'd like to cover in this. The first is that we've had a generation of agents, sonitinib, seraphonib, pisoponib, which are very similar to each other, what we call multi-targeted tyrosine kinase inhibitors. They target angiogenesis, new blood vessel formation which is very important in kidney cancer and they do it by hitting a receptor called VEGF-R2 and another number of other receptors. So I think they're more similar than initially we first thought. So we have very effective ways of controlling the kidney cancer with these agents for between nine and 12 months nowadays with the existing first line agents and the data that I'm reviewing at this conference is comparing two of those agents, sonitinib and pisoponib. And the bottom line is that in effectiveness terms, they are pretty similar. We couldn't see any statistically significant difference between them in a large study. And those data are presented by Bob Mox's data originally, presented by Kimmelo Porter at this conference. And then the other data I'm thinking about are with what I would call the second generation agents. So these are agents which are also similar to sonitinib, seraphonib, but they are more potent at hitting the key target and they are much less potent at hitting the targets we don't want to hit. So this is trying to give the idea that we have on-target things that we do want to do and off-target things that we don't want to do because they cause side effects without benefit. So the second generation of agents like tyvosinib and axitinib do cause side effects, but they cause on-target side effects. Things like high blood pressure, things like dysphonia, so you can get a hoarseness of the voice. Why that's on-target, we're not sure actually, but we do recognise it with all these agents and it correlates with how potent the agent is. And another thing sticking with the neck is that it can tone down the thyroid glands and hypothyroidism. We would consider all of those to be on-target effects. Examples of off-target effects are things like the skin rash, the hand foot syndrome that one gets, the diarrhea. We think those are off-target effects and another one which is important are liver function test abnormalities. So it's a question of balance between the side effects on the one hand and the effects on the other hand. Now when we're comparing data from the COMPAR study, which compares sunatinib, which is our existing standard of care with posopinib, which is a very similar drug, but used in a slightly different way, we find that in effectiveness terms there's really nothing between them. There's no statistical difference between them, but what there is is that patients seem to prefer the posopinib. So these are from a separate study called the Pisces study, where patients were given first one drug, then the other, and asked, which did you prefer? And neither the patient nor the doctor or the nurse knew what treatment the patient was getting. And 70% of the patients actually said they preferred posopinib compared to 20% saying they preferred sinusinib. So it's not 100-zero. Not everyone could choose between them. Most people could, but most people who could choose chose posopinib. We didn't see such a clear distinction in this COMPAR study. The purpose of the COMPAR study really was to check that you weren't swapping slightly more convenience and slightly fewer side effects for much less effectiveness, because I think that's a very difficult thing to square. So I would say that the bottom line of those data of importance today is that for most patients who have no liver problems, most patients would probably tolerate posopinib a bit better. It would be a bit more convenient. It would be a bit easier just to include it in your normal day. But I think that sinusinib is still a good drug and will still be better for several patients. Now, in certain parts of the world, you'll be able to get both drugs. In the part of the world I come from, you'll probably have to choose one or the other. So it may be more important data in one respect for me in that it helps me if I've got one shot, which shot do I offer the patient? So those are the data for today. There were also data for tomorrow, if you like, which I don't think are quite ready for prime time yet. The most advanced data are with a drug called tyvosinib. That's one of these second generation drugs, highly potent, highly specific. And that was compared with seraphonib, which was, I suppose, meant to be a drug which is easy to beat. Interestingly, we are much better at using seraphonib now. We recognize how to use it better. And so the results we're getting with seraphonib are really in exactly the same ballpark as the ones we're getting with seraphonib and tyvosinib. Interesting. I wouldn't say that's really established it as a first line of care at all. But in this study, tyvosinib was found to have a longer period of controlling the disease just over a year. It's the first time we've gone over the year mark for patients who've not had treatment before. And apart from these on-target effects, tyvosinib, with otherwise, pretty well tolerated. So we are getting hypertension. We are getting dysphonia, the changing of the voice. And we are getting toning down of the thyroid gland, all of which can be coped with, particularly the blood pressure, hypertension, and the thyroid gland. The dysphonia is trickier, actually. Although it sounds least serious, you can do less about it. And so for some patients, this is irritating. From my experience, it's not terribly irritating because it does happen with the other drugs as well. It tends to happen a bit more with these highly potent agents. So I think tyvosinib, you could say, well, it's a good drug. It should be available immediately. And in fact, the company has applied in the US to use it. And I think that would be a reasonable thing to do. So for somebody where quality of life is the number one consideration, and that's certainly my practice in the United Kingdom, there are quite a lot of patients. I would say tyvosinib is quite an attractive option. Other patients would feel efficacy and long-term survival are best. And we don't have those data reliably. In fact, interestingly, this study was mainly done in Eastern Europe. About 80% of patients came from Eastern European countries where the situation is very different from the US. Often no effective treatment is available outside a clinical trial. So in this trial, patients who got syraphanib were able to go on to tyvosinib after that drug failed, after syraphanib failed. But the same was not true, or the opposite was not true of patients who were allocated to tyvosinib. So after tyvosinib, most patients didn't get any other treatment. And that is one plausible explanation for why patients in the syraphanib arm going on to tyvosinib survived longer. So there is a significant difference there, but the data are early. And I think although the explanation I've given is plausible, just because it's plausible doesn't mean it's the right one. And I think we have to say that that is a caveat. My own feeling is that we can get a little bit bound up in detail in oncology. But I think this is quite an important distinction. I don't think we need another phase three trial to show that tyvosinib causes the same or helps the patient to live for as long as, shall we say, pysophanib or synitinib. Because I think that's going to take another three or four years. So I don't think we need another phase three study to compare survival. But I do think we need some data to show that the results we're getting for patients with tyvosinib are very, very similar to those we're getting with synitinib. So I think those are data for tomorrow. And the other data for tomorrow will, I think, be available sometime at GUASCO or ASCO next year are with oxytinib. So there is a first line study comparing oxytinib and other second generation with syraphanib, the drug that everyone wants to beat. Because it's meant to be the weakest of the available options. So I am expecting that we will have data for that drug as well. And I think those could be very persuasive data. And the importance of those would be that oxytinib could then be brought forward as a first line option. And I think that depending on how good those data are, that may well establish oxytinib as the agent of choice in the US, where it will be available first. In Western Europe, that would be much slower. So if you like, in my view, pysopinib has a period of time in the sun. But then there are new agents coming down the line. And the very last comment I want to make is that this is not the end of the story. I think we're very close to achieving all we're going to do with single agent tyrosine kinase inhibitors. But at this conference and other conferences, we've heard about new immunotherapies, new targets for drugs. We're going to get adjuvant therapy data, all of which may cause major benefits for patients in the years to come. And I think this is a really exciting prospect where hopefully we will be controlling disease for much longer. And of course, the golden chalice, if you like, is to get rid of it all together. I think there are two questions that everybody should ask their doctor when they get this sort of news. And the first is, can you tell me exactly what's wrong with me in my kidney and elsewhere in my body? Because that's going to determine what some of the treatment choices are. And I think that you do need to know these things. If, and I say if, not because I'm a particularly patronizing person, but because not everybody wants to make their own decisions. Some people want to listen to what the doctor, the nurse, the primary care physician suggests and do that. Other people want to be very involved in the decision. If you want to be very involved in the decision, then there are some basic things you need to know. And the first one is, where is my disease? What is my disease? And what other problems do I have? Those are all important because they will tell you, or they will tell your advisors, if you like, what treatment options you theoretically have. So for example, if the disease is limited to the kidney, surgery is going to be your best option. What kind of surgery? If you have disease in different parts of your body, is surgery really an option? No, probably not. It might be in a few cases, but usually not. So what treatments are available? Am I fit enough for them? What are the pros and cons of each of those options? So I think the second thing to ask is, what are my treatment options? Given what you just told me about, what's wrong with me? And tell me the pros and cons of each of them, please. And the last thing I would say is, there are very few decisions in kidney cancer which need to be made on the spur of the moment. Much, much better to take your time to reach a decision, not necessarily that you're happy with, it may not be a happy situation. But the important thing is to make the best decision for you. You must be satisfied with the decision and the reasons you've reached that decision. And if you're in two minds and you want to be guided, then ask for that guidance. And there are people who can guide you. The nurse specialists who are helping you are often extremely helpful at putting it in the right language rather than the sort of medical jargon that I and others often use. You need to understand the issues if you want to make the decisions. And most doctors and I think most nurses would like most patients to have a part in the decision even if it's not the whole part but a significant part. It just makes life much easier. You will do better in my view if you feel that the decision is something you can live with. Yes, the importance of asking questions is it's important at the time that you understand what you're told. If you don't understand what you're told, that doesn't mean you're thick. It means that you just don't understand what's been told. So we all break into jargon at times. Do please clarify things which are not clear. You are not wasting our time. It's one of the most important parts of medicine to make sure that you are communicating properly with the patient. And actually for me, it's much easier for somebody to say, hang on a second, I didn't understand that. Then for me to whitter on at length and then 10 minutes later, work out that actually stage A wasn't understood. So everything else that I've been going on about hasn't been understood either. So please, please don't feel embarrassed. We are there for you. You're not wasting our time. Much better to interrupt us. My name is Ulka Vaishampayan and I am the chair of the GU multidisciplinary team at Barbara and Carmina's Cancer Institute in Detroit, Michigan. This cancer center is an NCI designated comprehensive cancer center and affiliated with Wayne State University in Michigan as well. My practice and focus is genitourinary cancers, specifically within kidney cancer. My clinical practice is focused on kidney cancer along with the, as well as my clinical research is focused on kidney cancer as well. Patients get the awareness of not just new treatments because new treatments are frequently publicized all over the press, TV, newspapers, whatever, but they also realize or can, the information is transmitted about how we are fine tuning the existing therapies to serve them better. And the optimal treatment is still being decided for an individual patient. And we are really at the beginning of getting different genetic markers that may help us predict response. My presentation today is focusing within patient management issues of the disparities in treatment of kidney cancer. So even though we've improved outcomes tremendously in the last few years in kidney cancer, that in itself has caused a huge disparity gap to widen between the different people who don't have access to treatment, who have multiple other comorbid conditions that interfere with them receiving the optimal treatment and of course, race and socioeconomic factors as well as the biological factors within the cancer that induce all of these disparities. I think what patients should ask first of all is what is going to be the overall treatment plan? So not just the type of medication, but how are different modalities going to be integrated into their treatment? So probably the question needs to be, is am I a candidate for both surgery as well as receiving treatment by in terms of different targeted therapies or is it just going to be targeted therapies or some kind of systemic therapy first followed by the consideration of local therapies? So I think patients should be more aware in asking questions about consideration of multidisciplinary care. The other thing I think patients should become more aware of and be asking about is are there any clinical trials that are appropriate to my situation? Because typically what we find is that clinical trials in kidney cancers, especially in the last few years, have represented the most cutting edge type of treatment and has benefited majority of the patients who have enrolled on it. So I would say those would probably be the top two questions I would recommend patients ask. Sure, I did my training at the Cleveland Clinic for my residency and my fellowship in urologic oncology. I currently practice in Grand Rapids, Michigan at Spectrum Health, where I'm an associate professor at Michigan State University College of Human Medicine and also an investigator at the Van Andel Institute. So I'm a urologic oncologist, I'm a surgeon who serves as the research director for genital urinary cancers and is a lead in the clinical cancer program that we have at Spectrum Health. Patients with localized kidney cancer have a lot of options and I've presented evidence about all the various options that need to be considered. And what I tried to make very clear is that there's no one best treatment for all patients. There's a lot of things to consider and really the things that come into the fore are who's the patient and how many other medical problems are they encountering at the time of their diagnosis? What are the specifics of the tumor? How large is it? How complex in terms of deepness into the middle of the kidney? That impacts the success of various treatment options and the success of opportunities to spare the kidney. So those are important. And then the ultimate is the surgical factors and that can be impacted in great part by the center at which the person's receiving care, whose hands they're in in terms of receiving information regarding the types of options and also obviously what part of the country they live in because there are regional variations. We summarize some of the specifics and my task today was to talk about open partial nephrectomy. Well, partial nephrectomy is the largest number of patients will have this because the most patients with T1 renal cancer are candidates for it. Recent studies would show that at centers of excellence upwards of 90% of patients are able to keep their kidneys. If they have a small kidney cancer, four centimeters or less. And really for tumors even up to seven centimeters and select tumors that are larger, we are able to keep their kidneys. There's a variety of ways the surgery's done. One of them is with traditional open surgery. There's also minimally invasive options. So a laparoscopic approach to partial nephrectomy or a robot assisted laparoscopic approach. And again, there's varying techniques that can be used, but the important thing is to keep the kidney. And in the vast majority of patients with small renal masses, we can preserve the kidney. Absolutely. And so there's been a lot of discussion over the last decade about increasing use of partial nephrectomy, especially for smaller tumors. Some of these are slow growing. Some of them we even consider surveillance or watchful waiting in patients with significant medical problems. But for patients who are good surgical candidates and have small tumors, these are ones that we almost always can spare the kidney. So for smaller tumors, in almost every case, the kidney can be preserved. And so a partial nephrectomy is an option that enables a patient to keep their kidney and keep more of their kidney function. Even for medium-sized tumors, we can often do it. And so tumors that are even up to seven centimeters in size or bigger, partial nephrectomy may be an option. But what's the benefit to the patient? It's a real benefit in terms of kidney function. When you remove one kidney, as you'd expect, there's a significant change in kidney function. You might expect about 50% loss, but on average patients lose about 35% of their kidney function, because the one that stays in is able to take up some of the work for the lost kidney. But with partial nephrectomy, on average patients lose about 10 to 15% of kidney function. And so that's clearly less than with radical nephrectomy. For patients with perfectly normal kidney function, that may not be essential, but for many patients who are older or have diseases that can affect their kidney function, this is a very significant benefit to a kidney-sparing approach. So patients with hypertension, diabetes, kidney stone disease, coronary artery disease, smokers, or any of a number of other conditions that can affect the kidney, set up a situation where partial nephrectomy is clearly preferred. Patients with localized kidney cancer can expect great cancer outcomes if they have appropriate treatment. They can rest assured that cancer can be treated well. So the other thing they really wanna ask is, is there a chance to spare my kidney? And what does this physician or the surgeon feel are the chances that they can preserve the kidney? If they hear that their tumor is not amenable to a kidney-sparing approach, they might wanna check with that surgeon whether other surgeons would agree with that assessment that their kidney is not able to be salvaged because there's clearly some variability in practice patterns for small renal masses, right? So one essential question for a new patient to ask is, is a partial nephrectomy an option for me given the size of my tumor and the location of my tumor? If the answer's yes, that's good for their long-term outcome. If the answer's no, they might wanna double check and know that this is indeed the case that their kidney's gonna have to be removed, right? So second opinions are reasonably common for this disease because again, multimodality care is important. This is a disease where experts who are experienced in all the various stages of disease from early disease to locally advanced disease to metastatic disease are more comfortable with management and the different types of options that are available. The other thing to consider is that they're minimally invasive approaches, they're traditional surgical approaches and for patients who are not as good candidates, there are non-surgical alternatives. And so centers that have all of these techniques at their disposal can provide patients with a full spectrum of options. And the best possible care in any individual situation. I think it's important for patients who are newly diagnosed to get as much information as they can. The Kidney Cancer Association has wonderful resources available on the web and there are a number of written resources that are helpful as well. Absolutely, to know that you're not alone, that there's thousands of people across this country who have been in this situation before and through organizations such as the Kidney Cancer Association, you're able to get linked into patients, loved ones and providers who can really help you through with your condition.