Case 3: A 70-Year-Old Man With Metastatic CRPC

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Moving on to their last patient case, expert panelists review the diagnosis and management of a patient with metastatic castration-resistant prostate cancer.

Transcript:
Alan Bryce, MD:
Now, we’re going to talk about metastatic castration-resistant prostate cancer [mCRPC]. This patient is a 70-year-old man who came in with urinary obstruction, hematuria, and some low-back pain. He did have a history of hypertension. On initial work-up, his PSA [prostate-specific antigen] was 39.8 ng/mL, and he had 4 bone metastases in the pelvis. He was asymptomatic with a good performance status, aside from that low-back pain. Genetic testing showed no detectable alterations in his HRR [homologous recombination repair] genes. He started on ADT [androgen deprivation therapy] and docetaxel and had a nice PSA decline down to 0.6 ng/mL. Twenty-two months later, he’s having increasing fatigue. His PSA is rising to 25 ng/mL, and imaging shows lung metastases. He’s more symptomatic, as already described. Of course, he has castration-resistant prostate cancer, so abiraterone is added to his regimen. The first question—Eleni, I’ll start with you—is how has the evolution of the treatment of mCSPC changed the treatment landscape for mCRPC in your mind? What are we doing now?

Eleni Efstathiou, MD, PhD: This is a great question. You can’t help but think what of we’re going to be doing given the new data we just saw. The profile data that came through and the whole controversy there, what are we going to be doing in a year? The concern I have is that I don’t even see what you just showed us. If we’re going to be compiling everything in castration-sensitive disease, we may even have the enhanced antigen signal inhibition early on. It’s not a bad concern, because I agree that it increases the life span. We just need to start thinking more along the lines of what you proposed: let’s do that sequencing early on, potentially develop more of the liquid biopsies with ctDNA [circulating tumor DNA], and monitor the changes and the mutational events and alterations that may guide our practice. We heard great news last year when we got the data on the first targeted diagnostic-driven radiopharmaceutical, and it gave us a breather. Every day in the clinic, when you speak about this data, it gives the patients a breather too because we have something in CRPC. The landscape is changing rapidly. You described it as way into CRPC. I see it the question of what do we do after docetaxel and enhanced antigen signal inhibit coming up even earlier.

Alan Bryce, MD: Fair point. Dan, thoughts on that?

Daniel Landau, MD: It’s definitely a challenge. I’ve grown up with a belief of not necessarily keeping the best option in my back pocket, believing that I don’t know what’s going to happen by the time patients are ready for second- and third-line [therapy]. I want to give them what I believe to be the best early on, and that’s going to be a triplet while it could theoretically exhaust various options later. I still want to give the patient the benefit of the doubt and treat them the best way I can off the bat. For some of these patients who had prior docetaxel exposure, if it was awhile ago, there are times I go back to chemotherapy or cabazitaxel. We have some data about the benefits of switching from 1 oral to another vs introducing cabazitaxel in the right setting. It appears that there’s more benefit toward secondary chemotherapies than there are toward alternative oral agents.

The earlier treatments definitely play a role in what we’re going to do later. We’ve mentioned the testing a few times. If I have a setting to introduce something devoted toward BRCA mutations, I’m certainly thinking about that by the time patients are progressing. We’ll see how things work with Pluvicto, with lutetium. We’re very excited about the approval. The future is going to be very bright in that agent as well.

Alan Bryce, MD: Eleni, what about PSMA [prostate-specific membrane antigen] PET [positron emission tomography] imaging? When would you bring it in? Do you think providers need to worry about gallium 68 vs F-18?

Eleni Efstathiou, MD, PhD: I don’t get why we worry. For the time being, I’m worried about what can I get my hands on. But honestly, this is resolved. I agree with some data that the germline may be more specific, even though with the Pylarify option we’ve explored recently, I’ve been quite satisfied. I’m more concerned about our relying solely on molecular imaging and forgetting anatomic imaging. Also, to switch it a little, if we want to forget anatomic imaging, should we at least explore the opportunity to look at discordance in molecular imaging, PSMA expression vs straight FDG [fluorodeoxyglucose] expression that would speak to a more aggressive disease? If we combine nuclear medicine with good anatomic imaging, we might have a solution. The VISION trial had that point of looking at that discordance with anatomic imaging, but not a lot of that is discussed. It’s in the footnotes. My point is that I’m very concerned about relying solely on molecular imaging.

Alan Bryce, MD: No. 1, you can only order your PSMA scan when it’s approved by insurance. It ought to be approved if you’re trying to qualify a patient for lutetium. That’s clear enough. But we still live in this world, and it’s going to be uncertain for a while. One thing I struggle with a little—I’m not sure how much payers have picked up on this or if we’re going to have to deal with it—is that if you strictly read the FDA label for lutetium-177, it says that patients have to have PSMA expression using a PSMA 11 agent. Now, Pylarify is not PSMA 11. Gallium-68 isn’t necessarily PSMA 11. It could be PSMA 617, 1007. I don’t think most providers are thinking about this at all. But what are we going to do if they come down and say, “You have to have a PSMA 11 agent and it’s only available 2 hours away”? Because cross to half-life of all these gallium agents is shorter. The availability is different from F-18. F-18 has an advantage. I don’t know if that language in the label is going to be a problem for us, but in the back of my mind, it’s causing me a little worry.

Eleni Efstathiou, MD, PhD: I absolutely agree. It’s concerning for a lot of the practices, but we’re still finding our way in the dark. Do you have it available already, Alan?

Alan Bryce, MD: At Mayo [Clinic], we have it at our Rochester campus because we had an NDA [new drug application] in flight. We have an NDA in flight at the Arizona campus as well. I expect we’ll have PSMA 11 gallium-68 available fairly soon. But for a long time, I told patients, “If you can get a PSMA scan, I don’t care which 1 you get.” Don’t get on a plane to get 1 over the other, just get the 1 that’s available locally. I’m not sure that’s going to hold if the payers are strict about the label.

Eleni Efstathiou, MD, PhD: I was referring to if you have lutetium set up running right now?

Alan Bryce, MD: I’m sorry. We’re not giving lutetium yet because there’s no coverage determination.

Eleni Efstathiou, MD, PhD: We’re waiting for that as well.

Daniel Landau, MD: Same thing.

Transcript edited for clarity.