DR PETRYLAK: Sip-T is an immune product that is taken from patients. So in other words, they have a leukapheresis that’s performed. They have their mononuclear cells removed. These cells are then ex vivo activated with a fusion protein that contains a protein similar to prostatic acid phosphatase. So this is supposed to cause activated T cells. These activated T cells are then reinfused back into the patients, and this is where the antitumor effects occur from.
DR LOVE: So I want to find out how you’re integrating sip-T into your practice. Susan?
DR SLOVIN: I can tell you that one of the concerns that we’ve had is the fact that it’s a very good product. I would use it if somebody were to ask. I often present it as an alternative.
The problem with trying to sell, if you will, the immunotherapy is that there is no immediacy of response and that’s what people get very nervous about. They want to see something. And when you try to talk them through it, we say, “It’s immune therapy, we can wait as long as 6 months,” most patients, once they see that PSA start to double or triple in a very short period of time, are already sweating bullets and immediately want to do something. And that’s unfortunate, because I don't know where the antitumor effect, if any, is going to occur.
DR DREICER: So there’s no question this is one of the most tortured studies ever published in the medical literature in terms of its analysis and overanalysis. It’s the perfect storm of a therapy in a disease that is mounted by multiple different clinical subtypes, where a biochemical marker drives anxiety. And it’s an amazingly complicated thing to talk with patients about. So it’s time consuming. It’s problematic. The way I manage my patients with this is I talk about this as a therapeutic paradigm of a chronic illness and that this is a therapy with a different mechanism of action that is added onto the paradigm, does not replace anything, does not delay disease progression. I agree with my colleagues. For every 10 people I discuss this with, 1 or 2 will opt to proceed. Intelligent people who understand it, get it, say, “No. Thank you very much. I’m going to do something else.”
It’s a very interesting issue, I think, that as we begin to have additional data that’s immunologically based, we may reflect on this somewhat differently.
DR OH: Yes. I think the real problem is that patients feel very visceral about the treatments that they undergo. And despite our attempts to get away from PSA as a driver of decision-making about the effectiveness of a treatment, we’re still reliant on it. So it really does take time to prep the patient for this treatment, both because of the investment over that 5-week window when they’re actually getting the immunotherapy but also with regard to their expectations during and soon after the treatment.
DR LOVE: Oliver, how does sip-T fit into your practice?
DR SARTOR: I was one of these immunologic skeptics, and I finally kind of boiled it down in my own mind.
I said, “Okay. If you’re going to do a large trial” — and I don’t consider the first 2 randomized trials large enough to convince me — “then do a large trial and have it looked at pretty carefully and come out with a survival benefit, I’m just going to have to accept the results.”
It turned out I was the Data Safety Monitoring Chair for this trial. I looked at it pretty closely. And I don’t think it’s a highly “followed” trial. There’s a lot of criticism and examinations that occurred, but the bottom line is: You have a prospective randomized trial and it held up to scrutiny and you got a survival benefit. You have to look at it at a population basis. The way I talk about it to my patients is: It doesn’t cause a response. And some people don’t like that, and as Susan sort of said, a lot of people will opt for something that’ll give you a response. But on the other hand, you treat a population of men in this way and they live longer than the population of men not treated in this way. So I have a number of people who will opt for it.
We have it at our center. I use it within the FDA guidelines for asymptomatic/minimally symptomatic castrate-resistant prostate cancer. And I use it. I have no way of really determining if it works or not. I’m a little bit fascinated with some of these immunologic parameters that may be associated with a response. I really need to have more science. But I do use it.
DR BEER: So I think that’s why we have so much difficulty knowing how to use sip-T. There are so many alternatives. The sequencing studies haven’t been done. The magnitude of benefit that sip-T offers is no greater than the benefits we’re seeing with abiraterone and enzalutamide and may, in fact, turn out to be a little less. It’s hard to know, can’t compare across studies, but it’s certainly not a greater benefit than what we have with other agents. So I think our practice is no different from everybody else. We look for patients who meet the criteria, who have relatively slowly-moving cancer, where the battle is long and there’s ample opportunity to deliver the drug without having to deliver immunosuppressive therapy shortly afterward, prednisone-containing therapy within a month or 2 because they’re progressing.
DR DREICER: One of the interesting things — and we’ve all experienced this — is when you take the time to have a discussion with the patient or the referring oncologist — and I’ve had this happen every other month for many years — the oncologist will call me post sip-T when they’ve returned to their care. And they say, “How do you monitor the patient post sip-T?”
The difference between applying a therapy that has immune response possibility, which is a long-term issue, versus objective activity is very difficult for oncologists to get their hands around. It was the first therapeutic vaccine approved.
We have to change the way we think about managing disease as a chronic disease paradigm where we apply therapies based on, hopefully, rationale and science, which may impact on survival. But this issue about what to do, how to manage it, it’s all targeted around a marker, which we all acknowledge is a double-edged sword. It’s good and bad, and sometimes it really hurts us. But this is useful to talk about, but at the end of the day, you can’t think about it as a standard therapy. It’s not.
DR SLOVIN: We’ve got to be very cautious about using the term “immune response,” because when we think about immune response, immune response is just not a signal of showing antibody or a T-cell activation or proliferation. Instead, it has to really be correlated with a change in the biology of the cancer. So while we might see that a PSA will go up or down, it doesn’t necessarily mean that there’s a change in the metastatic disease that’s there, that something has remitted or regressed completely. So when we say “immune response,” one can easily be chastised just for using that without the concept that biology must be impacted upon.
The second is that this is a tremendously biased group, because we’re all in academic centers that favor investigational trials. So if a patient is obviously thinking about sipuleucel-T, they may opt for a drug that may give a faster response based on a clinical trial. The difference is, of course, on the outside, or the real world, people follow an algorithm they know. After this, they want to sequence that. And it’s very different than the way we often think within academics.
DR BEER: So in terms of describing how you take care of patients — and you guys will probably make fun of me for this, but I explain it a little bit like a very expensive and very complicated flu shot. On a population level, people who get flu shots do better. You don’t know who actually benefited. And you don’t really change anything you do after a flu shot. You keep taking care of them just the same as you would otherwise.
DR EISENBERGER: I just want to point out something we haven’t emphasized here. In our cancer immunology program, dealing with immunotherapies, one of the focuses is timing of immunotherapy. It’s possible that the interaction between immunomodulation and other treatments may be important. For instance, immunizing a patient before you give hormonal therapy, before you give chemotherapy. So it is also possible that immunotherapy may enhance subsequent treatment. And how you demonstrate that, that’s something that hasn’t been really done systematically in all the trials, because the trials that treat patients prior to chemotherapy don’t follow patients when they get chemotherapy because there’s no fixed point to initiate chemotherapy.
DR LOVE: I’ve got to just dip a little bit more into this. And let me try to throw it around a different way. Maybe this will be more interesting.
So Dan, about how many patients have you started on sip-T in the last year?
DR PETRYLAK: Probably about 30.
DR LOVE: Matt?
DR SMITH: Six or 8.
DR LOVE: Tom?
DR BEER: Ten.
DR LOVE: Oliver?
DR SARTOR: Twenty-five.
DR LOVE: William?
DR OH: About 10.
DR DREICER: Twenty-five.
DR SLOVIN: Two.
DR LOVE: I’ve got to say I’m surprised. I’m feeling a lot of skepticism in the room, and I know you see a lot of patients, but those are not inconsequential numbers.