Dr. Tim: So, if you take everyone in the trial, the difference between patients that receive Provenge and those that received Placebo was about a four-month overall survival advantage. But if you specifically look at those patients that were much earlier in their disease process with the PSA of less than 22.1, the overall survival advantage was 13 months. Drastically different.


Joel: Welcome everyone to this very important podcast. That's the one and only approved immunologic therapy for prostate cancer, Provenge or Sipuleucel-T. To discuss Provenge, we are very fortunate to have Dr. Tim Richardson, who received his medical degree from the University of Kansas School of Medicine. He completed his residency in Urology at the University of Nebraska in Omaha, Nebraska. Dr. Richardson is board certified by the American Board of Urology. Since 2012, he's at the Wichita Urology.


Welcome, Dr. Richardson, and thank you so much for joining us today and being willing to discuss Provenge. It is really our pleasure and we appreciate having you join us. First, if you don't mind, I'd like for us to discuss a little bit about what the immune system is and then of course, what Immunotherapy is? And importantly, how does it differ from the other prostate cancer therapies that we have?


Dr. Tim: In basic terms, the immune system is essentially our bodies' check system of identifying what in our body is normal and otherwise is foreign and needs to be eradicated. And whether it's a virus, bacteria, tumor cell, really anything that should not be there. Our immune system is our check and balance way of trying to eliminate those things that should not be there while maintaining and basically leaving alone the things that should be there. 


The theory behind Immunotherapy is essentially, how do we help our immune system? How do we help those cells that are supposed to be floating around and finding out what should be there and what shouldn't? How do we help those cells recognize tumor cells as foreign instead of looking at them as normal human cells? And how do we allow them to basically have an antitumor effect or cytotoxic effect on those cells to essentially help treat the cancer, decrease tumor burden, etc? That's the underlying theory behind Immunotherapy. 


There was a long period of time where simply no one believed in it. It's well recognized and widely utilized today, but for the longest time, it was just hearsay. People just thought, well, this is never going be a thing, we're never going be able to allow our immune system to help us fight these cancer cells, we're going have to rely on the standard cytotoxic treatments that we know. But that has slowly changed over time, thankfully, mainly over the last few years when you've seen a wide release of different Immunotherapy agents for all sorts of cancers, and in fact, you'll see the commercials on almost any TV program you're watching nowadays. So it's widely accepted today but that was not always the case.


Joel: We have all these other immune therapies for other cancers, but yet we only have Provenge for prostate cancer. And I've heard that prostate cancer has been defined as basically an immune desert. What's your thought on that? Any idea why we're so limited?


Dr. Tim: In many ways, prostate cancer is a much slower growing cancer than most other cancers and so you're just going see differences and responses and differences in the way that therapies interact. Some cancers will have an average survival of weeks or months, and even with widely metastatic prostate cancer, typically we are talking about the survival of years. So, it's just a much slower developing and progressing cancer and so I think that yielded a lot of skepticism as well with this slow-growing cancer. How are we ever going to train the immune system to recognize these cancer cells that are just too close to normal? 


In other words, the prostate cancer cells resemble normal prostate cells, its just way too much for our immune system to be able to recognize those as foreign, and really work against the cancers. I think a lot of it was just skepticism about Immunotherapy in general, but particularly when you're talking about cancer that is slower growing than most, it just adds to that skepticism, I don't think this is ever going work. I think that was probably the biggest hindrance to Immunotherapy with prostate cancer when this was released in 2010.


Joel: Provenge is effective, it does extend a man's survival so that means that somehow Provenge is able to recognize the cancer cells, even though it's slow-growing. Do you have any insight into the mode of action or what makes Provenge different so that it's able to do that, able to recognize prostate cancer cells?


Dr. Tim: Sure. Well, Provenge is different than the checkpoint inhibitors that we see today. Most of the kind of the latest and greatest immunotherapies that we're seeing on TV today that are released for other cancers, they're in the category of checkpoint inhibitors, and Provenge is different than those. A checkpoint inhibitor is essentially taking the brakes off of the immune system. I described to patients the immune system as a race car.  Unless you have your foot on the brake, it's going to fly through town at a hundred miles in an hour, you can't stop it. 


Receptors and antigens within the immune system act as brakes to basically slow down the immune system, to help the immune system recognize normal cells, identify foreign cells and just kind of keep the brakes on the immune system. These checkpoint inhibitors that we see today are essentially taking the brakes off. They're basically removing your foot from the brake, allowing your immune system to run much more readily and helping the immune system identify cancer cells easier.


Provenge is different than that, Provenge is not a checkpoint inhibitor. Provenge is essentially training your T and B cells, your immune cells to recognize antigens on the prostate cancer cell to, basically, help the immune system recognize that cancer cell is formed. Specifically, prostatic acid phosphatase as an antigen that is highly expressed on prostate cancer cells and if we train our T and B cells within our immune system to recognize that as foreign, they will more readily recognize prostate cancer cells as foreign and eventually generate a response that is an antitumor response.


Joel: Checkpoint inhibitors remove the brakes but Provenge, doesn't? Which actually leads to an interesting question. There are a lot of men who do have prostate cancer who also have autoimmune illnesses, illnesses like arthritis. Checkpoint inhibitors would remove the brakes on the immune system, which is already overactive and could actually cause havoc in the man's body. Is this a concern for men who have an autoimmune illness if they do think about taking Provenge?


Dr. Tim: It's certainly more of a concern with the checkpoint inhibitors. If you look at a side effect profile for checkpoint inhibitors, it's essentially a laundry list of autoimmune responses, whether it be Pneumonitis or Proctitis, Introitus, et cetera. So, the checkpoint inhibitors can essentially induce an autoimmune response by allowing the immune system to attack itself.


Provenge is not really amplifying the immune response, it's just helping the already present immune system be a little bit more target sensitive, meaning, be a little bit more specific, more like a rifle instead of a shotgun where it can specifically recognize prostate cancer cells as foreign. So, it should not really amplify the immune system and should not have near the effect for those patients that have an autoimmune disorder like it would with checkpoint inhibitors.


Joel: Can I assume that's still a good idea that a man considering Provenge makes sure that their doctor knows that they do have an autoimmune illness, so they can have a conversation--


Dr. Tim: Yeah.


Joel: About that?


Dr. Tim: Absolutely. It's always good to have a conversation with all of these different disease processes. But I mean, the more the patients educated, the better they're aware of this.


Joel: You and I both know that there are some doctors who remain skeptical that Provenge works, and I think a lot of the confusion comes from the PSA response that we see or we don't see right away. And of course, that pertains to the mode of action. I'm wondering if you could maybe speak to that point that will put men may or may not expect and what it means for them?


Dr. Tim: Sure. So. in many ways, we always thought that Provenge was before its time. In other words, we were not ready for it in 2010, there was already a lot of skepticism of whether any type of Immunotherapy would work for any cancer. So, you're already starting on a base of a lot of the population, just didn't believe in it. So, we simply were not ready for it. At that time, we did not understand fully how Immunotherapy even works. We did not understand the timeframe in which Immunotherapy works. So, when we saw that these short-term measurements of objective tumor response were not there, that created more skepticism. And so what we're used to with cancer are these objective measurements of tumor response, meaning, progression-free survival. Were the scans are looking better, the tumors are looking smaller or biochemical response for the cell counts are coming down or the PSA is coming down. 


These are short term measurements of tumor response. The gold standard measurement for long term tumor response is obviously overall survival. I mean, that is the gold standard and should be "Are we allowing these patients to live longer from their cancer?" that is the gold standard long term response. So when Provenge was released in 2010, we were really stuck on these short term measurements and so when Provenge came out and it did not really affect the PSA or the progression-free survival or how the tumor appeared on scans, that added to the skepticism.


But as years go on and we gained a better understanding of how Immunotherapy really works. Over time, that has allowed us to believe more in this therapy and allowed some of those naysayers to switch over to this therapy. And certainly, the recent influx of Immunotherapy with checkpoint inhibitors et cetera., has certainly added to that understanding and probably helped the acceptance of Provenge.


Immunotherapy works through several steps. There's first a primary immune response where essentially your immune cells are recognizing tumor cells as foreign and they're creating an antitoxic effect or antitumor effect. That's not an immediate process, that's actually a long-term process that happens over weeks and months. But then, that also leads to secondary immune responses through a process known as antigen spread. So, when the immune system attacks or reacts with a cancer cell, that either causes that cancer cell to die and release other antigens or maybe it just causes that cancer cells to express other antigens as it's trying to fight this immune system. And those other antigens also tend to be highly expressed on cancer cells and that will induce a secondary immune response. And this is a cascade that just happens over and over.


And as more tumor cells reacted with the immune system, more antigen spread occurs. It just builds on itself like a snowball. But again, this process is a very slow-moving, time-intensive process. This is not anything that happens over a couple of weeks where you see immediate PSA drop after starting androgen deprivation therapy, or you see the scans looking better, progression-free survival improved after starting cytotoxic chemo. This takes time, this owes a lot to the fact that in the studies over the first few years, we really didn't see any changes in the PSA or progression-free survival. But yet at the end of the day, we saw that these patients were living longer. 


So, Immunotherapy is more of a long-term therapy. In order to believe in Provenge, you almost have to really kind of understand the difference between how it's working compared to the conventional therapies because it is a time process. You need to allow the immune system time to have all these secondary and tertiary immune responses with antigen spread for its full effect. And I'm sure we'll talk about this in a bit but it led to some of the released data that the younger patients and the patients with less disease burden actually have greater results with Immunotherapy because they have more time to allow the immune system to work.


Joel: Are there any ways doctors who might remain skeptical could measure an immune response?


Dr. Tim: There's no great easy ways to do it in real-world medicine right now. Now, yes, you can use assays where you're monitoring for antibody response and looking for antigens that are present and kind of look at titers of whether those are going up. And in fact, many studies have shown that as time goes on after Provenge, you will see more and more antibody responses and more and more elevation of certain antibodies within the system. And that's from this antigen spread with secondary immune responses, etc. 


But there's no easy, readily way to monitor that in real-world medicine. Outside of the studies, there's no simple lab to check and say, ”Hey, I'm just working.” You just have to trust the science that, “Look, we know that this improves overall survival from the studies. We know that that's the best long-term result in the antitumor effect. So, you almost just have to trust the science and understand how it's working.” 


We hope that someday there will be better ways of easily monitoring tumor response other than just PSA, which by the way, is not the only measurement of tumor response, it's not even a perfect measurement of tumor response in prostate cancer cells, and PSA becomes less and less important. The farther down the path of disease progression you get, the microenvironment of the prostate cancer cells simply changes and PSA simply becomes less and less a prognostic factor down the road, especially in these metastatic castrate-resistant patients.


Joel: Listening to what you're saying reminds me that we actually have another podcast where we interviewed a gentleman by the name of Mark Hall. When Mark was diagnosed, he had a PSA of thirty-four hundred. He's now after treatment, which included very early Provenge from the time he was diagnosed. I don't think we would define a PSA that high as being early, but he had a significant response and he's got a number of years with basically been in remissions.


What I'm taking home from what you're saying is what's important is not PSA or the other biomarkers, but it's how long I hopefully will live. And there is based on the clinical trials and the data that's out there. If men who have Provenge are particularly early, which we'll talk about in a minute, will from a statistical standpoint, more likely live longer and that's really the bottom line. Would you agree with that?


Dr. Tim: I do and that's the point I push home to the patients and say, “Look, this is not necessarily going to change your PSA. We don't expect it to so don't get caught up on that. I understand that every other therapy I've given you to this point, we've used the PSA as a measure of response. This is not one of those, this works differently. It has a different effect on the tumor as a more long-term effect on the tumor. The goal of this medicine is not to decrease your PSA, it's to make you live longer. And there's no way we can measure that but we know that statistically within the studies on average, you will live longer if we do this, and even more so if we do it early.” I really help them try to focus on that overall survival benefit and just downgrade the PSA anxiety that comes along with this disease.


Joel: We have hounded into us as patients from the very beginning, our PSA, our PSA, our PSA and now all of a sudden our PSA doesn't have a meaning. … takes an adjustment, it's hard.


Dr. Tim: Sure.


Joel: Provenge clearly is the treatment that's a lot different than the other treatments we have and that includes how it's administered. Could you just take a few seconds and tell us how Provenge has administered?


Dr. Tim: Yeah. In the process of giving Provenge was also another thing that kind of hindered its release in 2010. In other words, Urology offices in particular. We're not necessarily ready or equipped for this process because it's something that they had never done before. But the process goes, the patient essentially goes either into an office setting or a blood donation center and they go through a process called plasma freezes. And essentially, that's the few hour processes where blood is taken from the patient and the peripheral blood mononuclear cells or the white blood cells are extracted from the patient's blood, and then the rest of that blood is given back to the patient. That process takes between three to four and a half hours, and it's called local Leukapheresis. 


Those white blood cells are then incubated with a recombinant fusion protein, which is basically it's a combination of the antigen prostatic acid phosphatase otherwise known as PAP, and PAP is highly expressed on prostate cancer cells. So, these immune cells are incubated with this PAP that you see on most prostate cancer cells in addition to a granulocyte macrophage colony-stimulating factor. So, this is basically a stimulating factor to amp up the immune cells and helps them recognize the PAP. This incubation period happens and now your T and B cells are basically trained to recognize prostatic acid phosphatase. That vaccine is then mailed back to the physician's office and the patient comes in to get that vaccine infused.


That visit for the vaccine infusion typically takes in the range of 30 minutes to an hour, typically at least in our office, an I.V. is started on the patient and they hang out in a recliner and that vaccine is infused usually over about 30 minutes. The patient typically does not have any side effects during that infusion time, but they might have some mild flu-like symptoms just due to the immune response, usually low-grade fever, chills, body aches, et cetera. But it's typically limited to the time of infusion or a few hours afterward. 


And that's really the process the patient goes through, they follow up in the office for 30 minutes to a one hour visit for the infusion. And they would do that a total of three times and there's two weeks in between each time. So, essentially, over a one-month period of time, the patient is getting three infusions and then they're done. Their immune system is trained for the rest of their life to help recognize these antigens, they never have to go through this again, it's not an ongoing therapy. And their body and their cancer are going to see a benefit from this over the rest of their life just from this series of infusions.


Joel: Actually, I'm going to ask your forbearance for a second. I just want to get on a political soapbox. There is talk with Medicaid and Medicare  lowering the reimbursement rate that physicians will receive for providing or giving Provenge and given the amount of time that doctors need to spend doing an infusion I remain concerned, along with many other advocacy organizations, that if the reimbursement rate is lowered, that we may see less and less doctors being willing to spend the time to-- because they’re just unable to.  Because doctors have to pay their rent like everybody in the other business. So I'm going to urge that people reach out to their members of Congress and tell them that they are concerned about lowering the rates of reimbursement. So that's on the side, I just needed to add that given what you described as the process.


Dr. Tim: Sure. Sure. And I would agree with that. I mean, if we already see it with patients that have Medicaid supplemental insurance to their Medicare, the Medicaid supplemental does not come close to covering that 20 percent portion of the cost of acquisition of the medication. So that drastically limits where patients can receive Provenge that have Medicare with a Medicaid supplemental and we see this time and time again in our office, and many hospitals are even refusing to give them that situation because of they simply lose too much money on it and that's only going to worsen as Medicare cuts reimbursement as well as Medicaid.


Joel: Right. So, we really as patients need to take a role here. Patients, their caregivers, their families, their friends, we need to make the effort, reach out to your member of Congress and let them know that this is something you're concerned about, you're watching. Treatment keeps us alive longer and that's what our goal here is. Anyway, if I get back to some of the other more practical stuff.


Provenge, basically, supercharges and sensitizes the immune system, but there are treatments after we've completed Provenge, that in kind of depressing the immune system. Particularly if you take Zytiga, you also have to take prednisone. And prednisone if I understand its mode of action, you'll depress the immune system. Is this a problem? And when is it safe for a man to move from Provenge on to another treatment?


Dr. Tim: Well, initially there was a fear that the Prednisone given along with Abiraterone was going to be immunosuppressive and suppress the effect of the Immunotherapy Provenge. We now know that's not the case, there have been studies looking at doing an immune response along with this dose of Prednisone and there has not been a change. In fact, the dose of Prednisone that is prescribed along with Abiraterone, it's what we call a physiologic dose. In other words, it's similar to the amount that the steroid that your body would already make and in a normal situation. 


So, it is not necessarily an immunosuppressive dose and we have realized that there really is not an effect on the immune response given along with Provenge. Now there is a theory that further treatments down the road after Provenge or in conjunction with Provenge could actually help the immune response. And there are several studies that are ongoing looking at this, but essentially the theory is, other treatments like chemotherapy, radiation therapy, et cetera., or antigen receptor pathway inhibitors cause cell lysis, cell death and essentially cause release or expression of other antigens. So that antigen spread mechanism of action that we talked about earlier where secondary antigens get expressed or released, which causes a secondary immune response. 


We know that that happens under the normal situation with just providing Immunotherapy, but it could be amplified by other treatments that will make it happen on a larger scale. Specifically, radiation helps kill cells in part through an immune response. Obviously Cytotoxic Chemotherapy, so there are studies looking at is there going to be a greater response with Provenge in combination with some of these other therapies. Mainly because that antigen spread effect is magnified. 


Joel: Recently there's been two-- what I can only call extraordinary data that's been released about the survival advantage of Provenge, specifically the potential advantage that it could offer to one class of men and also where their PSA is. We could spend just a little time talking about the data that I referred to and I think it's called basically the Schellhammer Data. While it's a little bit about that, I think this is a really important piece of information that men should consider as they move and progress through various treatments. 


Dr. Tim: Right, so if you go back to the original impact trial that garnered FDA approved in 2010, there were patients basically in all stages of the disease. There were patients that were very early with low PSA, there were patients that were very late with high PSA. In fact, the average PSA and the trial were actually very high. So, on average those patients were very progressed. But now that we have this foundation of understanding of how Immunotherapy works, how it takes time, how it's a long-term effect, and it's something that's going to take a long period of time to really kick in. Now that we have that foundation of understanding, it makes sense that we go back and look at, "Okay, who is going to respond better to this therapy?" Those that are in stage disease or more-- or those that are maybe healthier earlier in their disease process. 


So Schellhammer released his data, which was very, very nice to see this. He essentially broke the PSA into core quartiles. And he looked at those patients that had PSAs and each specific quartile and solve what was their overall survival advantage compared to the entire cohort. The smallest quartile were patients that had a PSA less than 22.1 and the highest quartile were patients that had a PSA greater than 134. And the total of the impact trial the overall survival advantage was roughly about four months. 


So if you take everyone in the trial, the difference between patients that received Provenge and those that received Placebo was about a four-month overall survival advantage. But if you specifically look at those patients that were much earlier in their disease process with a PSA of less than 22.1 the overall survival advantage was 13 months, so drastically different. 


In contrast to that, if you look at the patients that were specifically more advanced in their disease process with a PSA of greater than 134, you saw an overall survival advantage of only 2.8 months. So now that we have this foundation of understanding that, "Look, this is going to take time, this is maybe better suited for those patients that are healthier, maybe younger, earlier in their disease process, a lower PSA, a lower tumor burden." These are potentially the patients that are going to respond to this better because they have the time that it requires for this primary and secondary immune response to really take effect on the tumor. 


In fact, the PROCEED registry found additional findings that in fact, the younger patients fared better with better overall survival advantages. Obviously, patients with lower PSA did as well. In addition to that, patients with lower Alkaline Phosphatase levels fared better, which is basically a marker of tumor burden within the bones. Higher Hemoglobin, which is usually going to resemble a lower tumor burden in the bones and a healthier patient population as well as those patients with better performance status.


All of those patient populations fared better with Provenge with better overall survival advantages compared to those that did not. And specifically looking at different ethnicities, it's long been recognized that there are differences in the immune systems based on different ethnicities. Whether it be Caucasian, African-American, Asian, etc. So, one thing that they looked at was we know that African Americans tend to have more aggressive prostate cancer. They tend to be diagnosed with prostate cancer earlier, they tend to have more BRAF mutations.


We know that there is a difference in prostate cancer when you compare African Americans to Caucasians. So, one thing they looked at was, "Okay, well. how do these two different groups respond to Provenge?" And in fact, when they matched Caucasian and African-American patients for age in PSA so similar age, similar PSA, what they found was there was a huge benefit with Provenge if you are African-American. In fact, the overall survival advantage over Caucasians was 11.4 months. So now we know that the earlier you give Provenge, the better. The overall survival advantage is much more than four months, it's 13 months. In addition to that, if you have an African-American patient, you know that they're even more going to see a larger benefit and the Provenge compared to Caucasians. A difference of about 11.4 months. 


Joel: Yeah, that's really significant and it really punches holes into a lot of the skepticism. Can't tell you how often I've had patients say to me, "Well, I'm not going to do this treatment because all I'm going to do is live four months longer." Trying to get men to understand a statistical advantage does not have anything to do with what might happen to that person as an individual, and this is a great example. There are factors beyond just getting Provenge may well have a lot of effect on what your particular response might be and what survival advantage you might experience.


And again, as you said, the lower the PSA ideally being in the lower quadrant, it's going to give you a better chance of having better survival. And of course, ethnicity, that's an issue because we know that African-American men tend to be diagnosed later. They tend to be diagnosed with more aggressive disease. And I think that that's a public health problem that we need to tackle. But certainly, we need to begin in men who better responders, African American men, in this case, we need to make sure that they get on board quickly. That they're offered the treatments and that we deal with whatever the public health issues are that surrounds their inability to get treatment or their failure to get treatments. So, I think that's really important and I really think that for me, that's the take-home on this podcast, lower PSA. 


I will tell you this, that I always tell guys that my support groups, and I'm an outlier, I've been castrated sensitive for 13 years. The day that I know that I become castrate resistant is the day that I began the process of arranging to get Provenge. Was I know that the lower my PSA is when on castrate resistance, the better chance I'm gonna have of getting a survival advantage. And actually this leads to an interesting question, Provenge is approved for castrate resistance, many men who are no longer responding to primary ADT, Lupron, Tasha Dex, and those drugs. Why aren't then getting Provenge while they're still castrated sensitive when their PSA is or much lower? 


Dr. Tim: Well, we would all love to give it. Now that we understand that the earlier in the disease state you give it, the more the benefit there is. We would all love to give it earlier. Unfortunately, right now, it's only FDA approved in the metastatic castrate-resistant state, but there are ongoing studies looking at giving it way earlier, even in the localized disease state for patients that are on active surveillance. So, in our group, about 40% of the patients we diagnosed prostate cancer today, we put on active surveillance because we simply don't think that the cancer is aggressive enough to treat at that time. 


So, this is a patient population that is very earlier in their disease state that is relatively younger and healthier. And it begs the question, how will these patients fare if they get a vaccine for their prostate cancer? And potentially maybe that helps them never even need treatment for their prostate cancer. That study is called Provenge and that's an ongoing study that many groups, including ours across the country are taking part in. And we're all very excited about the study to see the results because forever we wanted to give this therapy earlier and earlier. 


Now that we have that understanding that it does work better earlier, this has been a big motivation of ours to try to give it as early as possible. I was having this conversation with an Oncologist last night and that going back to the skepticism of the four-month overall survival with the high-cost density of the drug. The drug came out it was in the upper 90s to around a hundred thousand dollars and people just saw, "Well gosh, this is too expensive for four-month overall survival." And I said, "Well now that we're better educated, don't think about that four months' survival." We know that if you give it earlier, it's more like 13 months, which is significant. 


So, the big motivation to groups now is exactly what you're going through with the castrate sensitive stage. You follow these patients closely so the immediate time that they become castrate resistant when their PSA is low, oftentimes even less than one, you can immediately get them onto Immunotherapy. 'Because you know, they're going to see a much bigger benefit. The other thing I say is, I say, "Look, how often do you give Abiraterone or Docetaxel to a patient who's newly diagnosed metastatic in the castrate sensitive space.?" And they say, "Oh all the time. I give it all the time." I mean, there was the results on overall survival were amazing that the overall survival advantage was 11 to 14 months. I said, "You're right, it is amazing." We'll look at this drug in a more advanced patient population with metastatic CRPC disease, if you give it early, the overall survival advantage is more like 13 months. 


So ,you have therapies that you're widely accepting and giving on a daily basis that have a similar overall survival advantage as this therapy which has, by the way, less side effects and has a similar overall survival. This just requires more education from us believers to the naysayer that over time we have a better understanding of how this works and what advantage there is. 


Joel: I'm glad you raised the economics because even though Provenge, which is given just basically you can do a course of Provenge in a month's time and it doesn't get repeated. The cost is certainly not any more than the other drugs that we're now giving men. When you lay it over the time that a man takes it, so you take the brand new second-line drugs and they're anywhere from seven to $12,000 a month, and if you consider that a man could be on that for a year to two years, it actually can exceed the cost of Provenge and yet the survival benefit may not be any better. So, it's really, if anything equitable as far as the quest versus survival, at least that's the way I look at it. I don't know whether you have any thoughts on that. 


Dr. Tim: Oh, I think you're absolutely correct. In fact, I would go a step further and say that the cost of the other therapies are usually or almost always more expensive than Provenge. Oral oncolytics for those of us that have a dispensary or pharmacies in our offices, we know that the Oral oncolytics, a cost to the insurance company is about 12 to $14,000 per month. And these patients aren't on these Oral Oncolytic for just one year. They're typically on these for two to three years on average. So that really quickly piles up to a higher cost than Provenge. 


In addition to that, if you compare a Provenge to the checkpoint inhibitors, the other immunotherapies that exist today, a year-long course of Immunotherapy can run as high as $250,000. So that's almost double the price of a single course of Provenge and there's also the potential for those other immunotherapies to be given more than a year for a prolonged period of time. If you compare Provenge to a yearly course of Docetaxel, you also have to add in the cost, not just of the Docetaxel, but there are multiple, multiple frequent office visits required throughout that year. There are multiple labs to be checked throughout that year. There are other infusions, for example, Neupogen are given along with the drug. There are prescriptions, say Provenge that or give Prednisone that is given along with the drug. 


There's the potential for transfusions for anemia, there's a potential for hospitalization due to neutropenic fever, etc. You throw all those into one bucket of a year course of Docetaxel and it's usually going to equal a higher cost than giving Provenge. So yes, the cost density is high, but if you actually look at, "Alright, it's not a four-month, it's closer to 13 months." If I give it early and if I actually compare this to the other therapies, could actually make the argument that it's more cost-effective than the other therapies. 


Joel: I would agree with you 100%. Very briefly, you mentioned a lack of or the lower level of side effects and you also touched on that earlier in the podcast. I think the side effects are really important. Men are very concerned about what side effects of treatment are going to be. They obviously want to know what is and how is goingto benefit me, but they're also going want to know what the cost is. We have the economic cost, which we just described, but there's also a quality of life cost. So, could you just stand a little bit on that? 


Dr. Tim: This is, a conversation I was having with the patient just a week ago who was skeptical of Provenge and read over the list of possible complications and just said, "I just don't want to risk any complications or side effects." And I said, "Look, let's look at the drugs that you're already on for your prostate cancer, the ADT, the Oral oncolytics, etc." Let's look at these. These actually have an exceedingly higher adverse event profile than Provenge. These on average will cause many more side effects than Provenge. And by the way, you're on these for a long period of time. You're on ADT for the rest of your life, you're on these Oral Oncolytic for probably the next few years. Provenge is just a one-month period of time. And by the way, even in that one month period of time, has less side effects than these other medications that you're already taking or any medications that I'm going to give you down the road. 


And then I just give them a typical patient scenario where I say, "Look, most of these patients come in and they don't have any side effects. They don't notice anything when they're getting the infusion." If they are going to have side effects, they're typically low-grade side effects, meaning during that time of infusion they have some flu-like symptoms. Those resolved pretty quickly on average. And again, this is a one-month period of time and on average it's going to be much better tolerated than the medicines that you're already on. And oh, by the way, these other medicines, you're going to be on these for a very long time, so you're going to be dealing with these side effects for a very long time. In Provenge, we're talking a one-month period of time. 


Joel: As we're coming towards the end of this podcast, I was wondering if you would mind just giving us two or three take-home messages from what we've discussed today, kind of summarize what you think are the most important points. 


Dr. Tim: Sure, I think maybe the most important is to educate people on how Immunotherapy is different than the other therapies. And I think if you understand that, that in and of itself allows you to believe in the therapy a little bit more. And so, the key to Immunotherapy I would say is time. It's a long-term effect, it builds on itself. It's like a snowball. It's nothing you're going to see right away. It does take time, it builds on itself to create a meaningful immune response. So don't be a naysayer just because it doesn't affect a PSA immediately or the progression-free survival. 


It is a long-term effect that does affect overall survival, which remains the gold standard for cancer treatment care. The other big thing is earlier is better. I mean that's the one big thing across the country as we now know that we want to give Provenge as early as possible because we know that if we give it very early, we have more time for that immune response to take effect and the patients are going to see a much bigger benefit. 


Joel: That's terrific. I would agree with you. Before we closed, another question for you. I know that you see patients, if patients want to make an appointment to see you, to talk about Provenge or any other treatment to deal with their prostate cancer, are you able to give out the way they could reach you or would you want people to reach out to me and then we can forward that information on to you? 


Dr. Tim: Sure. I'd be happy to whether it be with an email conversation or phone conversation, or if they're in the Kansas area, I'd be happy to see them. My office number here is 316-636-6100. My email is and of course, if they reach out to you and you get ahold of me, I'm happy to reach back to them as well. 


Joel: That's terrific. Thank you so much. We have a tradition here at Cancer ABCs, hopefully I'm not going to catch you too much off your feet here, so hold on. Our tradition is that I like to ask our guests if they would leave us with some sort of final words of wisdom or inspiration that you would want to offer to a man who as prostate cancer or to their family. I know you see a lot of men with prostate cancer. The word or words of wisdom can involve what we discussed today or anything else that you would like to talk about. I really would love to hear your wisdom for us. 


Dr. Tim: Sure. I just try to reassure the patients that are diagnosed with Metastatic Prostate Cancer and just say, "Look, Prostate Cancer has seen the largest growth and therapies that exist more than any other cancer over the last six to seven years and the future is bright as well. The future is more growth even still in any other cancer that exists, we have many therapies that are coming out and many new classes of therapies that currently don't even exist. And all of this has yielded a much longer average survival for those patients with Metastatic Cancer. So even though we don't want you to have Metastatic Prostate Cancer now is a better time than five years ago to have Metastatic Prostate Cancer because we simply have more tools to treat this. To allow you to live longer and die of natural causes instead of dying of your prostate cancer in a relatively shorter period of time." 


So I just usually give them that information to allow them to feel some optimism because it's tough to fill optimism when you have a metastatic cancer diagnosis. And we oftentimes have that conversation every time they come in with what's new, what's coming out, what are the trials that you guys are involved in. It's always important to provide optimism on a daily basis.


Joel: Thank you so much. And I think those are very, very wise words. Dr. Richardson. I would like to thank you very much for spending the time today to inform us about Provenge, specifically about the Schellhammer Data. And also, the fact that African-American men should definitely consider and talk about having Provenge put into their treatment protocol because they're going to get a great benefit or they should get a great benefit from it. 


The data is clear. The earlier a man, or should I say the lower a man's PSA is when he received Provenge is more likely to have a longer survival advantage. I think that the information you shared with us today supports the need of all men to get Provenge, especially when they first become castrate-resistant and of course, particularly African American men. As I mentioned before, personally I know the day I become castrate resistance is the day I think about making arrangements to get Provenge. 


This has been Joel Nowak from Cancer ABC's along with our most impressive guests, Dr. Tim Richardson, we have been talking about Provenge for men with Castrate-Resistant Metastatic Prostate Cancer, and the survival advantage that it may offer to them. Until our next podcast stays well, and remember, you might have cancer, but you should also continue to live your life and of course, to thrive.