Sequencing of LuPSMA Therapy in PSMA-Positive mCRPC

EP: 1.Role of Precision Medicine in PSMA-Positive mCRPC

EP: 2.PSMA-Positive mCRPC: Phase 3 VISION Trial

EP: 3.Patient Response to LuPSMA Therapy in mCRPC

EP: 4.Phase 2 TheraP Trial in PSMA-Positive mCRPC

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EP: 5.Sequencing of LuPSMA Therapy in PSMA-Positive mCRPC

Evan Y. Yu, MD: Regarding how sequencing occurs with lutetium-177 PSMA [prostate-specific membrane antigen]-617, I think it is all going to depend a lot on the FDA label. One never knows, but I suspect that they will have a similar disease state as what was done in the VISION trial, which will be that patients must have received prior AR [androgen receptor]-targeted therapies like abiraterone and enzalutamide. Patients must have received, I think, probably at least 1 taxane. The trial had some interesting criteria about receiving chemotherapy. The investigators and patients had to basically state that chemotherapy was not on the table. I do not know if there is going to be some label about whether a patient has to have received a couple of lines of chemotherapy, whether a patient will have to have refused chemotherapy, or be ineligible for chemotherapy. These are the sorts of things that I do not know about, and we are going to have to see what regulatory approval says. But if it is a looser label rather than a stricter label, I think what will happen is patients will receive either abiraterone or enzalutamide, or maybe both.

Patients will probably receive docetaxel chemotherapy—whether that is in the castration-sensitive or the castration-resistant setting, that might be loose in the label. Then, I would anticipate that patients would try to insert lutetium-177 PSMA-617, mostly because it is highly efficacious and it does not carry terrible toxicity. As a matter of fact, it seems less toxic than cabazitaxel in the TheraP study. Although I think cabazitaxel is a great agent, I think it is going be very easy to try to reach for this agent here. Patients will want it; it is new, and they have heard a lot about it being used in other countries. I think it will probably be used in that situation—post-AR–targeted therapy, post-docetaxel, and inserted right in there. Of course, we will have to see what the label shows, but that is probably where I would use it.

Just to summarize, overall, I think that it is very exciting for the field that lutetium-177 PSMA-617 is just around the corner. I think, if you look at prostate cancer, we have made a lot of advancements over the last decade, and this just shows that we are not slowing down. We have made recent advances that are focused on different gene alterations, genotypic precision medicine where we are doing next-generation sequencing, finding populations with cancer that might be driven by DNA repair deficiency, those who might be driven by mismatch repair deficiency, and having treatments to target that. This is a big population. It is not a small population. PSMA is probably highly expressed in 85% to 95% of patients with metastatic castration-resistant prostate cancer. The nice thing about this is it is a precision medicine target that really is highly represented in the majority of patients with metastatic castration-resistant prostate cancer [mCRPC]. I do not view this as a niche drug; I view this as a drug that the vast majority of patients with mCRPC can receive, and I think that is a real win for the field.

This transcript has been edited for clarity.