Using Taxanes Frontline in Metastatic Prostate Cancer


Nicholas Vogelzang, MD: Some of the other new agents that are along the pipeline of pathway or FDA approval include lutetium. Where do you see lutetium going?

Daniel Petrylak, MD: There are a number of trials that are looking at PSMA [prostate-specific membrane antigen]—based therapy linked with isotopes too in prostate cancer. I think these are going to be looked at in terms of competition to chemotherapy. There’s a randomized trial looking at lutetium versus dealer’s choice standard of care, such as enzalutamide or abiraterone, in patients who had failed other treatments.

I see this moving up earlier because, again, looking at the biology you do need PET [positron emission tomography] scanning to detect the PSMA-positive patients. Not all prostate cancer cells make PSMA, particularly the visceral disease that tends to have less PSMA expression.

The responses have been impressive—40% or 50% PSA-decline rates, objective soft-tissue responses. I do see this being integrated within the armamentarium. The question is, do you combine it with a checkpoint, combine it with other agents?

Nicholas Vogelzang, MD: You’re betting that lutetium is going to get FDA approval.

Daniel Petrylak, MD: I’m betting it’s going to get approved, yes.

Nicholas Vogelzang, MD: Do you worry about the bone marrow problem of lutetium?

Daniel Petrylak, MD: I do worry about that about time. We need more long-term data in terms of how the patients will react to it. Surprisingly, with radium 223 dichloride that has not been a problem. As far as the reports from the databases are concerned, you can safely give other treatments—such as chemotherapy—afterward. But it is something that needs to be monitored.

Nicholas Vogelzang, MD: Yeah. My 1 experience—I’ve had several experiences in people who have had radium—is that the lutetium is difficult to administer because of bone marrow issues.

Daniel Petrylak, MD: Sure, exactly.

Nicholas Vogelzang, MD: We do have to be aware that you can potentially damage bone marrow in these patients. Let’s try to wrap it up a little and think about the big picture. Let’s take now your current plan of treatment for a relatively young healthy patient who comes into your clinic with bone pain and high-volume disease. Where are you going to take this patient over the next 3 to 7 years?

Daniel Petrylak, MD: A young patient, bone pain, high-volume disease—that’s a patient to whom I tend to give docetaxel up front with androgen blockade. That would be my treatment of choice. Of course, what do we do at the time they become castrate resistant. It all depends on where their sites of disease are. If they’re bone only, if they have minimal pain, I tend to give sipuleucel-T right at progression. If they’re not bone only, if they’re visceral, then I tend to move chemotherapy up front earlier in these patients. The question, of course, is next-generation anti-androgens. How do you integrate those? Same thing, right after sipuleucel-T, I tend to go with ABI [abiraterone] or enzalutamide. Of course, we do see some visceral responses with these agents as well. Again, these are useful in this situation. You have to again tailor it to the patient. As the course goes on, they may need radium to take care of their bone pain. They may need cabazitaxel to also treat lymph node or visceral metastases. We tailor it based on the sites of disease, the molecular profile. I’m going to check for MSI [microsatellite instability]. I’m going to be checking for BRCA.

Nicholas Vogelzang, MD: Another question that comes up often is right now we’re using 2-drug therapy up front. We’re using either docetaxel and ADT [androgen deprivation therapy] or an AR [androgen receptor] inhibitor and LHRH agonist. Do you think we’re going to see a move to 3-drug therapy up front? When will that occur?

Daniel Petrylak, MD: I think we have to also keep toxicity in mind. That’s got to be the key because remember we are treating some patients when they’re older. I think we’re going to start seeing quantum leaps in survival with triplet regimens or multidrug regimens. That’s when we’ll start coming to play, but we’ve got to balance this against adverse effects and toxicities.

Nicholas Vogelzang, MD: Right. I believe the trial is darolutamide.

Daniel Petrylak, MD: Correct.

Nicholas Vogelzang, MD: It’s LHRH agonist, darolutamide, and docetaxel. I think darolutamide is the variable, so it will be LHRH agonist and docetaxel with or without darolutamide. Do you know when that’s going to report out?

Daniel Petrylak, MD: No, I don’t.

Nicholas Vogelzang, MD: OK. So that would be a practice changer as well.

Transcript Edited for Clarity

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