The Role of Sipuleucel-T in Advanced Prostate Cancer

Transcript:Raoul S. Concepcion, MD, FACS: A big point that I think we are promoting in the urology world especially is the concept of identifying these patients earlier because we now have all these great therapies that have a survival benefit. And one of the early articles that came out is looking at the IMPACT trial, which was the registry trial for sipuleucel-T in terms of looking at the PSA quartile data. So, Judd, can you walk us through the importance of this paper?

Judd W. Moul, MD, FACS: So, I think we’re all familiar with Provenge or sipuleucel-T, FDA-approved in 2010. If we think back five years ago, that was the first agent that started the train of the five or six new agents in prostate cancer, and it was controversial right from the start. It’s an immunotherapy; it’s custom made for that individual patient. For those who may not be familiar, patients come in for a plasmapheresis. The product is then sent to, currently, Atlanta. It’s an activated immunotherapy that comes back and then is infused in the patient. The patient receives three infusions over approximately four to five weeks. At Duke, our institution, we’ve been proponents of this product from the start. I think at one point we might have been the highest infusion center in the country.

Jorge A. Garcia, MD, FACP: You were, yeah.

Judd W. Moul, MD, FACS: It rotates potentially between Duke and UCLA and UCSF. So, we’ve been proponents of it, but it was always controversial. There was a 4.1-month median overall survival comparing patients who received Provenge versus patients who received a frozen version of it, some people call it “Frovenge,” but it was a group of patients who could receive an infusion. It was placebo-controlled, but then they could receive this other infusion. But the key teaching point is this overall 4.1-month survival benefit. The product was costly. It wasn’t that complex to administer, but it seemed complex, so it really never caught on at a lot of institutions. However, just to follow up on what you mentioned with Paul Schellhammer: the secondary analysis of the IMPACT trial looked at response and survival based on the starting PSA before patients receive the product. And that’s called the quartile data, breaking it down into quartiles of PSA. And the most impressive finding to me was that in those gentlemen who had a PSA of less than about 22. From a practical standpoint, a guy in your practice who has metastatic castrate resistant prostate cancer with a lower PSA, below about 25, the response to Provenge versus the placebo arm was striking, over a year survival benefit. And I believe that data; it makes sense from an immunotherapy standpoint. But from an academic standpoint, the challenge of the quartile data was it was a secondary analysis. It was never a pre-specified analysis with the FDA, so you basically had believers who think that that product makes sense and should be sequenced early. And then you have nonbelievers who just don’t believe that this immunotherapy should be used.

Charles J. Ryan, MD: I think one of the other questions is, does immunotherapy help all patients a little bit or a minority of patients a lot and a majority of patients not at all. That’s what that quartile data brings to my mind, as I look at it. I try to prognosticate: is this a person who’s going to live three years? And if so, sipuleucel-T may be a viable treatment for them. Of course, it’s really important to keep in mind that in the IMPACT study, there was very little to no penetration of enzalutamide or abiraterone. There’s a lot we just don’t know about the current era in using this agent.

Michael Fabrizio, MD, FACS: But if you think about immunotherapy, it should attenuate the disease, right? That’s how it’s working in other cancers. I mean, personally, if I could give Provenge at the time of diagnosis, at the time of their biopsy, that’s probably the most useful. Unfortunately, it wasn’t studied like that or approved. But if you think about it, it’s attenuating the disease.

Charles J. Ryan, MD: Maybe.

Michael Fabrizio, MD, FACS: It doesn’t have PSA. Maybe.

Charles J. Ryan, MD: The argument against that is that maybe those early patients don’t have enough antigen out there to benefit from it.

Michael Fabrizio, MD, FACS: Correct.

Charles J. Ryan, MD: So maybe the PSA below 22 or whatever it was in the lowest quartile are those who are in that sweet spot of having enough antigen and enough disease for their immune system to be attenuated. But we just don’t know.

Judd W. Moul, MD, FACS: I mean, I think the key point for urologists who are listening in on this program or watching this program is most of those patients with early castrate resistant disease are in urology practices. If it’s going to be beneficial, we need for the urologists to identify those patients, be aware of it, and either do it themselves or refer those patients to a center of excellence where it can be administered.

Raoul S. Concepcion, MD, FACS: But I think it is incumbent on the urology world for just what you said. I mean, it’s made it into the guidelines now. So, when you look at the American Urologic Association guidelines, they’ve tried to go through and find good level 1 evidence. They’ve tried to take into account performance status. Clearly, the most beneficial patient is going to be that index patient 2 that’s completely asymptomatic, has a significant survival to their overall health, and would hopefully see a benefit from immune therapy. And then the most recent guidelines that came out in 2015 basically say the same thing. If you’ve got an ECOG 0 patient who’s going to live at least 12 months, who’s completely asymptomatic, you should be, again, considering sipuleucel-T, but then you run into the whole controversy of the layering and the sequencing. Again, like the discussion with radium, there’s no PSA effect, so we have to kind of bring people off the ledge, that their PSA level correlates with efficacy.

Michael Fabrizio, MD, FACS: You hear that argument less now about the PSA effects, but I would say it’s a fairly innocuous drug, if I can use that word. I mean, you get a little low-grade fever, at most, with the infusions, which we rarely see. So this is something that you have strong evidence for. You can debate the studies, but it’s there, and there are two of them, and you could give this drug with relative ease in that metastatic castrate resistant arm.

Raoul S. Concepcion, MD, FACS: And I think like Chuck was saying, one of the things that’s so important to these patients, because many of them are asymptomatic, is this concept of preservation of quality of life. They can get this therapy, and Judd, like you said, it’s three infusions within four to five weeks. It doesn’t slow them down; they continue to play golf; they continue to take their grandchildren places, mow the lawn, or whatever.

Judd W. Moul, MD, FACS: A couple other practical points: as a urologist, I kind of get fewer callbacks from this than I do with BCG. So it is well tolerated. Just to follow up on Mike’s approach with radium-223: at Duke, we have a central coordinator. We have a physician’s assistant. This is her project, and so whether it’s a urologist or a medical oncologist, we can work with our PA (our Provenge PA, we call her), and get it done. And the drug can be written by either urology or medical oncology. It gels the team, too, because we’re working with the same coordinator.

Transcript Edited for Clarity