PSMA Clinical Trials Offer ‘Another Tool in the Toolbox’ for Prostate Cancer


As part of its Speaking Out video series, on behalf of Fans for the Cure, CURE® spoke with Dr. Daniel P. Petrylak about PSMA, what it is and how it is advancing the prostate cancer landscape.

Kristie L. Kahl: Can you explain the use of PSMA and what it is?

Dr. Daniel P. Petrylak: So PSMA has been around since about 1990. This is a membrane protein that sits on the surface of the prostate cancer cell. It actually is a folate transporter, strangely. It was originally looked at in terms of trying to develop a blood test similar to PSA. PSA has its own advantages and disadvantages . But it really is not shed into the bloodstream. It is distinct from PSA, I think it's important to note. PSMA is expressed in practically all prostate cancer cells, probably about 90%. It's also expressed on the vasculature of other tumors. But interestingly, it's not in the blood vessels of prostate cancer. So, it's a bit of a paradox. And people can’t explain that observation.

So there have been a variety of different ways of trying to image prostate cancer using PSMA. And that's really been evolving over the last 20 years or so. There was a previously (FDA-approved agent…which used an antibody that recognized an internal epitope of the PSMA molecule, so it was not as accurate because it really didn't catch what was on the outside of the cell. And it wasn't as easily admissible. So it really picked up dead cells in that situation. But nonetheless, it was FDA approved. And there were some drawbacks to it: a lot of false-positive (results). And so there have been newer next generation PSMA imaging techniques used. These involve PSMA gallium, other ligands that recognize PSA aside from monoclonal antibodies, and these are more sensitive in picking up prostate cancer than let's say, for example, standard CT imaging or bone scans.

Kahl: Where are we currently with the use of PSMA?

Petrylak: So right now, we have several different PSMA tests, imaging agents, that are approved for detecting prostate cancer. And these are predominantly being used right now for detecting occult disease. So if we have a patient who comes in, negative CT scan, bone scan, a rising PSA, we potentially can identify sites of disease that may not be picked up on the scans for treatment of oligometastases or determining whether disease is truly localized. Additionally, it's being used as an imaging agent to select those patients to be treated with isotopes, particularly PSA lutetium. And those patients who image positively are more likely to respond to these particular antibody or these isotopes.

Kahl: Can you discuss some of the trials we should be keeping our eye on?

Petrylak: Well, the VISION trial evaluated PSA lutetium in patients who had failed or had progressed after a taxane-(based chemotherapy) and next generation anti-androgen (therapy), and this was compared to best supportive care. And that showed a survival benefit in favor of PSMA lutetium. There has been another trial to compare PSMA lutetium. This is a randomized phase 2 (trial) that showed that in comparison to cabazitaxel, this had a better progression-free survival (the time from treatment to disease progression or worsening), but there's no overall survival (the time from treatment that a patient is alive) difference. So those are the two trials I think that are important that have come out recently.

There's studies that are now moving these agents up earlier. There's one trial that's looking at this in hormone-sensitive disease, giving PSMA lutetium along with hormone therapy and then potentially seeing if this will improve survival as well. There's been a trend as with all of our agents such as chemotherapy, next generation anti-androgens to move these upfront and the treatment of diseases.

Kahl: What do we have to look forward to with PSMA in prostate cancer?

Petrylak: Right now, I think it's a another tool in our toolbox. It does improve overall survival. It does improve progression-free survival, but it is not a cure. And I think that's very, very important for patients to remember. It's a another treatment regimen that we can use. And it does offer a different target than immunotherapy, chemotherapy or hormones or, for that matter, targeted therapy with agents such as (Lynparza [olaparib]) and (Rubraca [rucaparib]). So, you have to discuss with your doctor, when's the right time to administer this in relationship to the other treatments.

Transcription edited for clarity and conciseness.

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