Alicia Morgans: Hi, I am so excited to have here with me today, Dr. Oliver Sartor, who's a Professor of Medicine at Tulane and who is a primary author on a study of Sipuleucel-T through the PROCEED registry where we really looked at trying to understand outcomes of African American men in addition to Caucasian men who were treated with Sipuleucel-T. Thank you so much for being here with me today.

Oliver Sartor: Thanks, Alicia. My pleasure.

Alicia Morgans: Wonderful. Oliver, can you tell us a little bit about the PROCEED registry and why it was so important to get this work done?

Oliver Sartor: Sure. A little bit of history, and I might add this is a little bit odd, as the Sipuleucel-T was approved by the FDA, there the potential signal for a neurologic series of events, which the FDA requested that we study in more detail. A group of us, Tia Higano, and myself, and Andy Armstrong included, were part of a team that helped to structure this registry and would look prospectively at adverse events as well as a variety of patient outcomes. Well, when we put this together, it really was an opportunity to gain wonderful natural history data for people treated with Sipuleucel-T. This was coming from a wide variety of community-based practices as well as academic practices.

One of the issues that had come out early on, and I'm giving credit to David McLeod, who was a urologist at Walter Reed, retired now, and he pointed out in the initial prospective Sipuleucel-T trials that the African Americans seemed to be doing exceptionally well. This is a very, very small patient sample and one that really was considered to be unreliable because the confidence intervals were so large. One of the things that we did after talking with Dave was to build in this concept that we ought to be looking at African Americans and their outcomes over time. The recent publication emphasizes just that point.

Punchline: African-Americans do better. When we look at this data, we wanted to be absolutely certain it was not simply due to a confounding variable. African-Americans typically do worse as you typically know for patients with prostate cancer, but they are now a series of articles that would suggest that perhaps with abiraterone that African-Americans might do better with docetaxel they might do slightly better and even with radium they might do slightly better. Now there's kind of a coming together of issues in CRPC that suggest that African-Americans may do better, but nothing that we've seen before compared to the magnitude of the benefit that we've seen in the Sipuleucel-T treated patients.

Here, the hazard ratios were very, very much in favor of African Americans. In fact, it's almost twice as good with regards to overall survival. Well, there are many endpoints that you can somehow fudge or are misinterpreted. Overall survival I think is the most important outcome. We balanced all the factors in multivariate analysis, looked at match type analysis. African-Americans did better particularly those with relatively low PSAs. To me the implications are Sipuleucel-T is an agent that we want to use in a variety of asymptomatic patients for the low PSA, but particularly for African Americans that we assessed with that data suggest.

Alicia Morgans: Absolutely. A lot of the concern about PROVENGE® back when it was initially utilized or Sipuleucel-T was that we really just don't know in which population this drug is going to work most effectively. We don't know what are the ways that we choose our patient population. In this setting it looks like at least giving the opportunity for men who are of African American descent is probably going to be a key factor when we're using this. Again, I think you and I both tried to get every available life-prolonging therapy into patients who have advanced prostate cancer to give them the opportunity to benefit, but this is going to be especially important in our African American patients.

Oliver Sartor: I agree completely, Alicia. One of the things and I'm going to cite a paper about Paul Schellhammer who looked at the IMPACT Phase III study, which was the trial that got the Sipuleucel-T approved. In the trial design, which by the way did include a crossover for some patients after progression, it turned out that the patients who were treated with Sipuleucel-T as compared to the control group really did much better if they had a low PSA at the time of trial entry.

Paul Schellhammer, still active by the way, but the former president of the AUA and very distinguished individual in my own mind, divided the IMPACT cohort, the Phase III Sipuleucel-T cohort, into quartiles and looked at the hazard ratios in terms of survival. There was no doubt that those with the lowest PSAs were the ones who seem to benefit the most. It turns out that our similar analysis done for the PROCEED made the African Americans look the same. The hazard ratios were most improved for African Americans as compared to Caucasians for those with the lowest PSAs. I think that's an important message we need to get out. If this therapy is going to be used, earlier is probably better.

Alicia Morgans: I totally agree. Actually, although I don't use an absolute PSA cutoff, I do try to get Sipuleucel-T to patients who have, of course, asymptomatic or very minimally symptomatic disease, which is also often going to be a population who's relatively early in the mCRPC journey. This is the time when their PSAs are low and when I think they'll have the maximum opportunity to really benefit from therapy.

Oliver Sartor: I agree completely.

Alicia Morgans: Absolutely. You did mention this cerebrovascular event question, one of the reasons that the team put together the PROCEED registry. What did you find in terms of cerebrovascular events?

Oliver Sartor: Really nothing. I'll give you a little bit of an oddity here. I was actually the Chairman of the data [inaudible] monitoring committee for the IMPACT trial. I reviewed the data very, very, very carefully when that trial, prior to it being published. When we looked at the data, there was an improvement in overall survival and you needed to do a timed analysis. In other words, it's not just the number of events. It's also the number of events as a function of time. We really were not able to see anything. As it turns out in the PROCEED registry we really did not get any signals. I think that that initial concern raised by the FDA turns out not really to be a concern.

Alicia Morgans: Important, though, that there was due diligence looking into it, doing a large prospective study of well over a thousand patients to hammer that out. To find a nothing is actually quite reassuring, I think.

Oliver Sartor: It is. I mean what we confirmed is that flu-like symptoms can be problematic for a few, but it really doesn't interfere with therapy. The vast number of patients actually get their treatments on time. The PROCEED Registry does give a couple of thousand patients with real-world experience and real followup the opportunity to be studied. We have additional publications coming out. Tia Higano has a publication out now, one of the publications out, and there'll be more to follow.

Alicia Morgans: Wonderful. As you're giving a final message then to clinicians who are thinking about using Sipuleucel-T for their patients who have metastatic CRPC, do you have any overarching message or a message for them as they're trying to use this data?

Oliver Sartor: Well, simply say that African-Americans are likely to have benefit compared to Caucasian populations from Sipuleucel-T, but I think that the prospective randomized control data indicates that Sipuleucel-T can prolong survival for many individuals with this disease and that we should rest assured that well-conducted Phase III trials can translate into clinical practice, but particularly for African Americans.

Alicia Morgans: Wonderful. Well, thank you so much for putting this data into context and sharing your expertise with everyone. I really appreciate your time.

Oliver Sartor: Absolutely. Thank you very much.