Novel Approaches to Optimizing Management of mHSPC

Discussion on the selection of therapy for a patient with metastatic HSPC in the context of available agents and FDA approvals.

Robert Dreicer, MD, MS, MACP, FASCO:
Dr Scholz, tell us your approach. This guy is in the office. How are you counseling him, and what are your thoughts about management?

Mark Scholz, MD: I concur with Dr [Saby] George in terms of the reapplication of the PEACE1 and ARASENS data to this type of patient. Whether someone previously had local therapy, I don’t think that changes the general character of someone who has metastatic disease. There are concerns about the patient’s age. When we start adding docetaxel and perhaps darolutamide, it’s a concern, but it looks like it should be manageable. Sometimes I’ll talk to patients and say, “Why don’t we try 1 treatment and see how you feel, see how well you tolerate that initial cycle of docetaxel? If it’s well tolerated, we’ll proceed accordingly.”

Back to the PSMA [prostate-specific membrane antigen] PET [positron emission tomography] scans, because we’re all going to be hearing about this. PSA is a marker for response and survival. PSA is a super powerful way to determine what’s going on with these treatments. Now that we have a better systemic scan, such as PSMA, we’re going to want to get a baseline PSMA head scan prior to starting treatment. Then as we would with a medical oncology patient who didn’t have PSA, we would get scans after 3 and 6 months.

When we get into these more advanced stages, a subgroup of people have cancers that don’t make as much PSA. It’s possible to get mixed responses. One consideration that may be extrapolated from the oligometastatic patients is that if you treat someone with widespread metastatic diseases, the patient probably has many metastases. When you get the PSMA PET scan, there may be 5, 10, or 15 metastases or more. But after treating to a complete response, if he gets an undetectable PSA, will he also have complete disappearance of disease on PSMA? If so, should those few oligometastatic leftover spots be treated with spot radiation?

Robert Dreicer, MD, MS, MACP, FASCO: It’s a provocative approach. In terms of level setting where we are, we don’t have any evidence at all with the use of PSMA PET in the setting in which we’re talking about, in terms of using it as a response parameter. Even in the setting of PSMA lutetium-177 or other radiopharmaceuticals that are PSMA targeted, we don’t know how to use those studies to follow up, to assess response, to understand whether people should get more treatment, etc. We all anticipate that PSMA PET will be more broadly applied to the mCRPC [metastatic castration-resistant prostate cancer] setting based on potential regulatory approval rule of a therapy that’s going to require a companion diagnostic. But it’s important to recognize that we don’t have the prospective evidence yet to understand that. This is a good time to reiterate that every drug we’ve talked about during this program was approved on the basis of phase 3 trials using conventional imaging.

All of us who work and take care of patients with this disease recognize that 1 of the potential dangers, the Pandora’s box that we open by using PSMA PET, is that there’s the potential to undertreat some patients. For the locally advanced patient who might have been treated with curative intent but now has a scary PSMA PET, we say, “We can’t cure you, so we’re not going to try.” There’s the patient in the setting where a PSMA PET shows these 2-mm equivocal uptakes in the peritoneum, and we don’t know what to do with that; you apply even earlier intensification. As Dr George mentioned earlier in some of his conversations about some of the drugs we’re using, we know there’s morbidity with these agents, and it’s not abiraterone and maybe increased cardiovascular morbidity. There’s increased cardiovascular morbidity with all the drugs we’re talking about to some degree, and there are other toxicities. We’re beginning to enter an environment where we’re going to start doing things and we’re going to have to learn, but it’s important not to leave our audience with the understanding that even if you could do these tests, somehow we’d know how to interpret them. This is an experienced panel where you’ve been using these assays, and you’ve got significant experience in this disease set. It’s another thing to try to generalize that in the absence of evidence.

Transcript edited for clarity.

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