Fine-Tuning Immunotherapy to Treat Prostate Cancer Recorded on: April 24, 2013 John Corman, M.D. Medical Director, Floyd & Delores Jones Cancer Institute at Virginia Mason Virginia Mason Medical Center Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That s how you ll get care that s most appropriate for you. Hello and welcome to Patient Power. I'm Andrew Schorr. Each year thousands of doctors from around the world gather for the annual meeting of the American Urological Association, and among the things they discuss is the latest news about advanced prostate cancer, and this year we're particularly interested in news about immunotherapy. To help us understand we have with us a leading researcher in the field. That's urologic oncologist Dr. John Corman. Dr. Corman is the medical director of the Virginia Mason Cancer Institute in Seattle. Dr. Corman, thanks for being with us on Patient Power. Thanks for having me. Dr. Corman, so you're a urologic oncologist. One of the studies you've been involved in is the ProACT study about sipuleucel-t or Provenge. Tell us about that news and what it means for patients. The study's primarily about fine-tuning Provenge, fine-tuning sipuleucel-t. We know that patients who receive sipuleucel-t (Provenge), who have advanced disease, have a survival benefit, and it's by using a certain concentration of the medication. This particular study is going back and looking
at different concentrations of the same medication to see a couple of things. Number one, is it safe; number two, to see if giving different concentrations of that medication results in the same immune response or a similar response; and ultimately, of course, to see whether different concentrations result in the same or even better survival benefit. And it's the first two issues, the safety and the immune response, that the study at the AUA is commenting upon. Okay. So what do we know now? We know that the drug is safe given in varying concentrations, both at the concentration that was initially studied, and then in lower concentrations the medication is equally safe for patients. And we also know that, for all three concentrations that were studied, a similar immune response was mounted by patients who received the medication. The study would imply that you don't need to receive the highest dose of the medication in order to mount an immune response against PAP which is the protein that sipuleucel-t (Provenge) targets with the immuno-event. You mention that we don't know the survival benefit of these different concentrations yet, but that information is sure to come out eventually. Is the hope that, as we get this information we'll be able to have different dosages for different men, just like we have for other cancers? That's the hope. The survival data takes many, many years to be mature, and until that's available, until that data is mature, we won't be able to comment on what the actual numbers show. But, yes, the hope is that we can tailor the medication for given patients. In immunotherapy, you mentioned fine-tuning. So we're in a refinement period? I think that's exactly right. You actually take the whole field of immune therapy and prostate cancer and go back several stages. For years we've known that men have the ability to mount an immune response against prostate cancer, we've done this work, others have done this work. Whereas you take 20-year-old, you take 30-year-old men and you ask their immune system to recognize and to fight cells that look like prostate cancer, at least in the laboratory, those cells have the ability to do so. 2
What happens as that person, as that organism ages, that allows prostate cancer to occur? What has happened to the immune system that impairs its ability to mount an immune response? And the answer to that is, we don't know. But sipuleucel-t, Provenge, which has been FDA-approved, clearly shows that you can stimulate the immune system and patients can have a survival benefit because of that. What we don't know is, when is the exact right time to give the medication, who is the right patient population to receive it, how often should they receive a booster or should they receive a booster of the same medication, what is the exact proper dose to be given of the same medication. I think your analogy of fine tuning is spot on. We know that it works, and determining the right time, the right duration, and the right dose, is the next level of assessment. I know those studies are ongoing, so we'll look forward to that. Let's talk about other immunotherapies a little further behind and not yet approved. You've been involved in the study of something called Prostvac-VF. I understand that's taking a virus and combining it with a drug, making a whole new drug out of that. Where are we now with the study of Prostvac-VF? Absolutely. It's building upon this theme of immunotherapy having a role in prostate cancer. It's a different take on immunotherapy. Sipuleucel-T (Provenge), which we've been talking about, is constructed from a patient's own dendritic cells, cells that are drawn from the patient's body, stimulated in the laboratory and given back to the patient. Prostvac, which is a drug that is not FDA-approved, as of yet, but is in clinical trials, is an off-theshelf medication. It is a virus that has been infected, if you will, with a PSA gene as well as other molecules that are intended to help stimulate an immune response. And those are injected into a patient over a course of several weeks, with early data showing efficacy and suggesting a survival benefit, and for that reason this medication is being used more and more in a controlled phase 3 study to look for, ultimately, a survival benefit in patients who receive it. And then there's another potential drug, one that has been around for a while, studied, then the studies were stopped and now they're on again, GVAX. What is GVAX, where do we stand with it now for prostate cancer? 3
The GVAX story is fairly complicated. GVAX itself is a platform upon which several different therapies are built. There is GVAX for pancreas cancer, there's GVAX for lung cancer, and there's GVAX for prostate cancer. GVAX for prostate cancer was essentially studied over the last, oh, six or seven years, and it actually was quite far along in terms of development. Some recent studies, that were completed about two or three years ago, had some safety questions with the medication, and for that reason, immediately, the studies were halted. Now in going back and looking at that data, with more of a fine-toothed comb, it looks like those safety concerns may have been overstated or that the benefit from the drug may not have been initially as appreciated as perhaps it should have been, and for that reason several centers are again considering looking at GVAX in specific settings. Prostvac and GVAX, both immunotherapies, could have some role for men in the future? Right. You have to remember with urologic oncology, immunotherapy has a long, long history. To bladder cancer, we've used immunotherapy in the form of a medicine called BCG for many, many years and has a clear benefit in terms of preventing the recurrence of bladder cancer. Kidney cancer, we've been using a medicine called IL-2 (interleukin 2) for many, many years, which in certain patients offers a survival benefit. The concept of stimulating the immune system, to fight urologic cancer, isn't a new one. It's one that actually has a long track record of some successes. One last drug I wanted to ask you about is not an immunotherapy but seems like it might have some promise. It's a drug already approved for the treatment of melanoma, Yervoy or ipilimumab. Where does that come in for prostate cancer? All right. I think that that's another drug which is actively being researched right now. Ipilimumab (Yervoy), I think, many of us think of as an adjunct to additional therapy so it can help potentiate the effect of other immunotherapies. Ipilimumab's (Yervoy) action is actually to enhance the role of lymphocytes, and their ability to fight cancer. So, Dr. Corman, as a urologic oncologist, how do you feel about the range of research that you and your peers are doing now for late-stage prostate cancer and also looking at it for earlier prostate cancer, as well? 4
I think that's the key. When these new drugs are brought to market they are often, or they're almost always studied in patients with end-stage disease. Those patients have received years and years of therapy. Perhaps they've had their pelvis radiated which could only hurt their bone marrow or their immune cells. They've had surgery. They've had years of hormone therapy. They've had chemotherapy. All these things inhibit the immune system. If we know that immune therapy works in them, just think about how much more potent or how much more powerful it could be, at least in theory, in patients with earlier stage disease. And so that's why we've done things like looked at Provenge, the sipuleucel-t that we've been talking about, look at Provenge in a neoadjuvant setting, giving it to patients prior to receiving a prostatectomy, when they have the earliest of stages of disease, or looking at these therapies before patients start receiving hormone therapy or chemotherapy. I think as these agents are proven to be safe, as they're proven to be efficacious in later stages of disease, the movement is towards bringing them earlier and earlier in the compendium of prostate cancer and hoping that the effect is going to be even more profound. As a specialist helping men with prostate cancer, are you excited about where we are now and where we may be headed? Yeah. It's a remarkably exciting time to be taking care of prostate cancer patients and urologic oncology patients, in general. There are new fields that we have available to us, and new drugs we have available to us today, that we could only dream about 10 years ago. And so, when you think about the next three or four years and the drugs that we've talked about, that are new in development, and multiple other ones that are earlier in their stages of development, it's a very exciting time. Dr. John Corman, medical director of the Virginia Mason Cancer Institute in Seattle and a urologic oncologist devoted to patients and to research, thank you so much for being with us. My pleasure. Thank you. 5
Seems like there's a lot going on when it comes to immunotherapy for prostate cancer, and that gives us all a great deal of hope. I'm Andrew Schorr. Thank you for joining us. Remember, knowledge can be the best medicine of all. Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That s how you ll get care that s most appropriate for you. 6