Patient advocate Jeff Folloder conducts an in-depth discussion on emerging immunotherapy approaches for advanced prostate cancer with MD Anderson Cancer Center experts, Dr. Sumit Subudhi and Dr. Jeri Kim. Walking us through developing treatments, including vaccines and checkpoint inhibitors/immune modulators, these experts refer to today as “transformative times” with individualized therapy as the new standard of care.
Transcript
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Jeff Folloder:
We spoke a little bit about immunotherapy. Let’s get focused on that with a little bit of a laser beam here. Let’s talk about what’s on the horizon and what’s happening in clinical trials with immunotherapy.
Dr. Subudhi:
So first is PROSTVAC-VF, which is an experimental treatment. And it brought a lot of excitement because in a small clinical trial, a Phase II trial that was randomized to placebo, there was an improvement in overall survival. And the way this vaccine works is that you get seven total injections.
And the first one is—well, I should say the vaccine is just not a normal vaccine. But it has the ability to teach your immune system to attack PSA. So—and PSA is something that our prostate cancer makes. In addition, it has three other elements to it. It targets ICAM-1, LFA-3 and B7-1.
These are co-stimulatory molecules—fancy word to say these are things—molecules that help further boost the immune system. So the immune system is trained to recognize PSA with a triple boost of—with the LFA-3, ICAM-1, and B7-1. And you get seven of these injections, and it’s currently being tested in a large Phase III trial that I believe has stopped accrual, and now we’re just waiting for enough time to figure out which arm survives longer.
Now in this trial, there were actually three arms: one with PROSTVAC-VF alone, another one with PROSTVAC-VF plus a cytokine called GMCSF. That’s something that’s Dr. Kim alluded to earlier. This cytokine helps stimulate your dendritic cells to become activated and presents this PSA to the T cells to attack your prostate cancer.
And then the third arm is just the GMCSF arm alone, to see—and that’s the placebo arm.
Dr. Subudhi:
Okay. GVAX is another experimental drug, and basically, that takes prostate cancer cells—not your own, but another person’s prostate cancer cells that we’ve been using in a laboratory for years. The two prostate cancer cells are PC3, which stands for prostate cancer three, and Lymcap, which is lymph node prostate cancer. The cap is—stands for prostate cancer. So those two cell lines are then engineered to express the cytokine GMCSF.
And they’re reinjected into the patient’s body. And in those trials, it did not show to improve overall survival, and so I think GVAX as a therapy alone is not gonna proceed in prostate cancer. But it may be in the future in combination with other treatments.
The other one is ProstAtak, and that’s something that’s not for advanced prostate cancer. It’s more for localized prostate cancer.
Dr. Subudhi:
And so what happens is, for those patients who can potentially be cured with surgery alone, or radiation alone, in these patients, they don’t get the surgery. They get radiation, and they get three injections—one about two weeks before the radiation, one a few days before the radiation. Then they get radiation to the prostate, and then finally, they’ll get one more injection of this. You take this with a pill called valacyclovir.
Why do you do this? This is called the suicide gene approach. What it is is that the injections that they’re putting into your prostate introduce a gene into your prostate that when you take this oral pill, it kills the prostate, okay? So that, with the radiation, is thought to boost your immune system and cure you for life.
Jeff Folloder:
So in layman’s terms, the idea of vaccine therapy is to introduce something into the body that lets the body first see the problem that’s there and then encourage the body to attack that problem. Is that a fair…
Dr. Subudhi:
…that is fair. I just want to make it very clear. This is very different from how we deal with infections, right? A lot of us have children, or ourselves have been vaccinated.
And when we’re being vaccinated for infections, those infections are not within us. We’re trying to prevent the infection. But when it comes to cancer vaccines or prostate cancer vaccines, you already have prostate cancer. And now we’re asking the vaccine not to prevent but actually to kill your prostate cancer. That’s a larger bar and more difficult bar to obtain, and I just want to make that clear. That’s very different from how we deal with infections.
Jeff Folloder:
But the scenario at play is there’s a cancer inside our bodies. And for whatever reason, the army in our body isn’t paying attention to the cancer. We’re trying to wake the army up and say, “Go do your job.”
Dr. Subudhi:
So we’ve got—so this theory that you’ve just brought up has been around from the early 2000s, and we couldn’t prove it. But now we’ve recently been able to prove it in our animal models, and now we’re proving it in our patients. But the concept is that patients’ immune systems have been fighting their prostate cancer for years.
But it’s not until the prostate cancer becomes smart enough to evade the immune system that it becomes clinically apparent, meaning that’s when you end up showing in our clinic, and we’re like, “Oh, you have prostate cancer.” But before that, the immune system was fighting the cancer and keeping it in check.
Jeff Folloder:
Now we just have to figure out a way to get that army to fight a better battle.
Dr. Subudhi:
That’s right.
So I’m just gonna lump these next five drugs as one—they’re basically one class of drugs known as checkpoint inhibitors or immune modulators. The way these work is that I’m gonna bring up infections and the whole lymph node thing again when I talked about having a sore throat.
And you can imagine that if we have a virus or a bacteria that’s giving us a cold, that the immune system is revved up to fight it, right? Now if there [weren’t] brakes on the immune system, you can imagine that lymph node or the swelling would just keep going and going until it burst. Well, our body knows that that’s not good for us, so it finds a way naturally to bring it back to normal. So they put brakes on the immune system.
Those brakes were discovered in the 1990s, the mid-1990s, and in 1995, one of the scientists, Dr. James Allison, who’s here with us at MD Anderson—he discovered, when he was at Berkeley, that you can create a drug to transiently remove the brakes off the immune system. The first drug ever developed, and is probably the main drug talked about, is ipilimumab, or Yervoy, and it was first used in patients in the year 2000.
And basically, again, the way this drug works, it removes the brakes off the immune system, allowing the immune system to then fight the cancer. And these other drugs are all just finding—removing brakes from a different part of the immune system.
Jeff Folloder:
Now, these drug names are very difficult to pronounce. I get that. But on several of them, I noticed three letters at the end, M-A-B.
Dr. Subudhi:
Yes.
Jeff Folloder:
And because I was one of those Type A, I’ve gotta learn everything patients, that stands for what?
Dr. Kim:
Antibodies. Antibody.
Jeff Folloder:
Monoclonal antibody, right?
Dr. Kim:
Yes, yes.
Jeff Folloder:
Are these antibodies that we get from other people? Do we invent them in a lab? What makes monoclonal antibodies special?
Dr. Subudhi:
Okay. So we all make our own monoclonal antibodies.
But these are different. These are engineered in a lab to specifically bind to high affinity to the brakes on your immune cells. And so they’re engineered in the lab and then made in mass production so that they can be used in clinic.
Jeff Folloder:
Now, are these types of drugs widely available?
Dr. Subudhi:
So, yes and no. If you have prostate cancer, the answer is no. If you have melanoma, then drugs like ipilimumab are widely available, because it’s the standard of care.
But right now, they’re—all these checkpoint inhibitors are experimental in prostate cancer, and we have two clinical trials that we’re running here at MD Anderson that are utilizing some of these drugs and several more to come.
Jeff Folloder:
So we’ve gone through the checkpoint inhibitors.
Dr. Subudhi:
Can I add one more thing to it?
Jeff Folloder:
Sure.
Dr. Subudhi:
Okay. So as opposed to vaccines, vaccines don’t seem to change—let me back up, sorry.
Vaccines don’t lower your PSA. Or when you have scans done, you won’t see your bone metastases disappearing or your lymph nodes shrinking. It just slows down your cancer, okay? And that’s why people tend to live longer with the vaccines. With these checkpoint inhibitors or modulators, you can expect, in about 20 percent of patients, 10 to 20 percent of patients that get this therapy alone, not in combination with anything else—you can expect to see a PSA decrease, your scans to improve with time.
And time is a key point here. It can take up to two to three months to see this happen, unlike chemotherapy or those hormonal therapies that we discussed earlier. And finally, the major thing about these checkpoint inhibitors is that, like you, who had a modulating drug, they can lead to durable or even curative responses. That’s something that we don’t see with the vaccine immunotherapies.
Jeff Folloder:
So you used a pretty important word there—very casually, very calmly. You said the word “curative.”
Dr. Subudhi:
Yeah.
Jeff Folloder:
So what’s on the horizon? Would both of you say may tend to provide more intense, more high quality of life outcomes for advanced prostate cancer patients? That’s the goal of this.
Dr. Kim:
Absolutely. Right. And I think that just to mention that since 2004—so just looking at the landscape of prostate cancer treatment. So 1999 was when we had mitoxantrone (Novantrone) approved by the FDA. 2004, docetaxel (Taxotere) was approved by the FDA. And since 2010, we have five different agents approved by the FDA for treating patients with advanced prostate cancer.
So we are really making great advances in prostate cancer treatment. And with all these promising agents, and including immunotherapeutic agents that are out there and being developed, that we’re trying to combine all these different agents to improve patient survival. And so we are really in—yeah, I think just an exciting time, and things are very—I think it will be transformative.
Jeff Folloder:
So improved progression outcomes?
Dr. Kim:
Not only that. Eventually cure. I mean, that’s our goal. Right.
Dr. Subudhi:
It is. And I think that, before I go on to adoptive cell therapy, I want to bring up one point. I think one of the things that we’ve failed to do as a field is: we’ve been treating prostate cancer as a one size fits all. All of you have different prostate cancers, and we’re learning—we’re appreciating that now, and we’re realizing, hey, you know what? Some people need chemotherapy upfront. Some people need immunotherapy upfront.
Some people need hormonal therapies upfront. And we’re starting to learn, what are the clinical characteristics? What are the markers in your blood? What are the different genes that your prostate cancer has that will tell us which type of therapy you need? And I think that’s gonna be the biggest advance, in addition to the combination therapies, to help us cure prostate cancer.
Jeff Folloder:
So the concept of individualized or customized care is moving into the treatment of advanced prostate cancer.
Dr. Subudhi:
Absolutely.
Jeff Folloder:
This is one of the most important concepts that I think can be communicated today. One size fits all is not the standard of care that you should expect. You should expect to be able to ask questions like, what is my specific game plan? How is this going to affect me as an individual, as opposed to just a general patient?
Dr. Subudhi:
Yeah, because we have a lot of patients that come see us and say, “Hey, my buddy had this type of prostate cancer. How come he got this different treatment?” Well, first of all, that’s tough for us to answer, because we don’t have the entire clinical history of their buddy. But second, it’s probably because each prostate cancer is different, and we try to personalize it.
Now we can talk about the adoptive cell therapy. So adoptive cell therapy, in this case, they remove your immune cells, in particular, your T cells, out of your body. They genetically engineer it to help it fight prostate cancer, and then they reintroduce those T cells in your body to then kill the prostate cancer.
This has not been—it’s still experimental. There seems to be some promise, but my gut tells me this alone is not gonna be the answer. It’s gonna be in combination with probably the checkpoint inhibitors, where we’re gonna see great value in this approach.
Published By :
Patient Power
Date :
Feb 02, 2016
