Charles Ryan: Hello from PCF 2019. I'm joined by Dr. Matt Rettig who is a professor of medicine at UCLA and is the Chief of the Hematology and Oncology Division at the Greater Los Angeles VA. And importantly, he's leader of a national effort to unite Veterans Administration hospitals around prostate cancer care and prostate cancer research and has a lot of work going on that's of interest to the health of veterans with prostate cancer.

Thank you so much for joining us. So you have, I'm really impressed, now a large portfolio of clinical trials going on exclusively within the VA system for men with prostate cancer in addition to broad genomics efforts and other things. Tell us a little bit about the action items that are going on in the VA right now in prostate cancer.

Matt Rettig: Yeah. Really what we're trying to do with this program, we call it POPCAP, which stands for precision oncology program cancer of the prostate, is to deliver precision oncology to veterans throughout the United States. There are 9 million veterans that have been enrolled in the VA and receive their care at the VA and what we're trying to do is use some sort of molecular biomarker, typically a genetic sequence through next-generation sequencing, so that we can match a specific genetic lesion with a specific therapy.

And that's largely being conducted in the context of clinical trials that with each trial having a specific genetic lesion or lesions to which the genetic lesion is matched with a therapy. But we're also able to deliver care through off-label use of drugs and occasionally on-label use of drugs that are premised on a molecular lesion in prostate cancer that's not very common.

Charles Ryan: So for veterans who are watching this and are wondering, should I go and get my tumor sequenced, or how do I do that, to whom does it apply? Every veteran with prostate cancer? Only those who have recurrent disease? Who are the people who are following up in this program?

Matt Rettig: Right. It depends what sequencing we're talking about. If we're talking about sequencing of their tumor, we're largely talking about patients with more advanced disease, metastatic disease. They should walk into their VA hospital with their DD 214 form and say, "I want to enroll," if they're not enrolled. And you can get enrolled in the same day. It's easy. It's quick, it's not...

Charles Ryan: And they don't have to do anything because it's just the tissue that's already in the pathology department.

Matt Rettig: That's right. If the patient has been diagnosed in the United States at the VA, then their tissue is there. If they've never been to the VA, they can enroll and they can start getting care including precision care. And if they have tissue that's outside of the VA system, it can be requested. And that tissue can be used for the genetic analysis. Alternatively, in some situations we can use blood as a source of tumor DNA or we can do a fresh biopsy when there is no adequate material available.

Charles Ryan: Okay. So the veteran has done this. He's signed up. He's getting his tumor sequenced. What happens if there's a positive result? Does he get called about the big clinical trial? Does he have to talk to his oncologist about it? What's the process next?

Matt Rettig: Typically, the genetic sequencing process would occur through the oncologist. If the oncologist doesn't offer it, the patient to bring it up with their oncologist. Okay. And what we have in the VA system is a national database of all the patients who are undergoing genetic sequencing. And what we're trying to do, and we're in the process of doing, and I think it's going to come to fruition very shortly, is that we will be notified when a patient has a genetic lesion. And part of this program that we're conducting throughout the United States is we're trying to bring in every veteran, irrespective of where they are and we'll pay for their travel room and board to come to a VA medical center to get precision care if it's not offered at their local VA.

Charles Ryan: You'll get an alert about a positive, let's say a BRCA test of a veteran somewhere. You may call the oncologist in that local VA hospital where that patient's being seen and possibly bring them to Los Angeles or bring them to wherever the local, Minneapolis, where the local VA is for enrollment in the trial.

Matt Rettig: Exactly. If for some reason that mutation can't be acted upon at their local VA, whatever, they don't have the resources, the knowledge. That's exactly right. We can bring them to the closest VA medical center that's executing appropriate clinical trial.

Charles Ryan: Okay. How many veterans do you estimate are living with prostate cancer now, getting care at the Veterans Administration hospitals?

Matt Rettig: I know that number pretty precisely. It's about 488,000 veterans.

Charles Ryan: So an incredible amount of people.

Matt Rettig: Yeah. Yeah. They're alive with the diagnosis of prostate cancer and there are about 16,000 that have metastatic prostate cancer that are alive.

Charles Ryan: But you have 485,000 veterans whose pathology's in the VA system.

Matt Rettig: So there are about 485,000 that are alive in the VA system. Not all of them have had their pathology in the system. We know the precise number and we know that where those samples are within the VA system. So we can request them if necessary. But I would say about 40, 50% of them actually have their sample within the VA system.

Charles Ryan: Got it. So just briefly in the last minute here, the clinical trials that you have are testing what kinds of therapies?

Matt Rettig: They're testing therapies that are called either PARP inhibitors or some of the novel immune therapies, the checkpoint inhibitors. We're also building studies that involve targeting other genes that seem to be driving prostate cancer. So for example, there's a type of mutation called an ATM mutation. It's a mutation that's similar to the BRCA mutations, but a lot of the drugs that work for the BRCA mutations are not seeming to work in the ATM. So we have a clinical trial that we're building where we target a cousin of ATM called ATR, and we think there's this process called synthetic lethality. It's a yin and yang where if one is knocked out and we then knock out the other, the cell dies.

Charles Ryan: So the data that you're getting from the genomic sequencing from the veterans is leading you towards understanding what's driving that individual veteran's disease and also pointing you towards a specific therapy for that individual person.

Matt Rettig: That's precisely it. That's why we call it precision medicine. Tailoring the therapy to the individual patient.

Charles Ryan: And the exciting thing is this is happening outside of the Veterans Administration. In a previous generation, the Veterans Administration might follow, but here you're really leading.

Matt Rettig: We're trying to lead the way.

Charles Ryan: You're doing clinical trials that I would be delighted to have in my non-VA hospital. So it's really exciting to see that.

Matt Rettig: Thank you.

Charles Ryan: And congratulations for your work and for really leading this effort nationally and all that you're doing for the veterans in the United States and for advancing the care of prostate cancer.

Matt Rettig: Well, thank you for giving me the chance highlight the work.

Charles Ryan: Pleasure talking to you.

Matt Rettig: Thank you.

Charles Ryan: Yeah.