A Look at Lutetium-177-PSMA & Analyzing the VISION Study

This interview is part one of a roundtable led by Dr. Daniel George, Professor of Medicine, and Surgery in the Duke Cancer Institute, featuring Dr. Oliver Sartor, Medical Director of the Tulane Cancer Center; Dr. Preston C. Sprenkle, urologic surgeon and a urologic oncologist at Yale University; and Dr. Rana McKay, GU medical oncologist at the University of California-San Diego.

In this segment, the roundtable panel began an “inspiring discussion” around lutetium-177-PSMA for the treatment of advanced prostate cancer. Dr. Sartor provided a brief review of the VISION trial, which assessed standard of care plus or minus lutetium-177-PSMA for patients with significantly advanced metastatic castration-resistant prostate cancer that had previously failed hormone treatment.

Dr. Daniel George:

Hi. My name is Dr. Daniel George. I’m a medical oncologist at Duke University, Professor of Medicine, and Surgery in the Duke Cancer Institute, and it’s my pleasure to moderate this session today for GU Oncology Now. With me today are three of my colleagues. I’ll let them introduce themselves.

Dr. Oliver Sartor:

Hi, Dan. Glad to be here today. I’m Oliver Sartor, a medical oncologist. I’m the Medical Director of the Tulane Cancer Center down in New Orleans, and really a pleasure to be able to have good folks like you to chat with today.

Dr. Preston C. Sprenkle:

Thank you, Dan, for the opportunity to talk with you guys today. I am Preston Sprenkle. I am a urologic surgeon and a urologic oncologist at Yale University.

Dr. Rana R. McKay:

Thank you so much, Dan. I’m Rana McKay. I’m a GU medical oncologist at the University of California in San Diego. It’s so great to be here with you.

Dr. George:

Fantastic. Well, it’s good to have you all here. We had a fantastic GU ASCO, our Genitourinary Cancer Symposium just last month, and a lot of new data coming out in prostate cancer and a lot of excitement coming for some new therapeutics, including the lutetium-177-PSMA data based on the VISION study which we heard and read about last year.

At this year’s GU ASCO, there were several abstracts that really highlighted some post hoc analyses from these. I thought we could start by diving into some of this work, and in particular the things we’re learning now, the implications of this work going forward.

Oliver, maybe you can start us off. There was some work looking specifically at some predictors for response of resistance to lutetium-177-PSMA based on some other imaging parameters besides the liver. Do you want to walk us through some of that data?

Dr. Sartor:

Sure. I might just give a little bit on the VISION trial itself in case people are not familiar with it. VISION trial was really pretty simple. It was standard of care plus or minus PSMA lutetium-177, and all the patients were very advanced metastatic CRPC and that all failed a novel hormone like abiraterone, at least one and maybe more, and that all failed at least one taxane.

It turned out that there was no role survival benefit, and very specifically the inclusion criteria use PSMA PET selected patients, so the criteria we used in VISION was to look at a metastatic region as defined by uptake greater than liver, and the liver’s a little bit of an arbitrary… and I’m not really sure that we know how to optimally choose patients, but I’ll simply say that there are other ways of doing it. You can set an SUV cutoff and maybe have the SUV cutoff higher rather than lower, and there’s going to be a little bit of variation from patient to patient.

Another way to look at it instead of SUV is looking at it like the parotid. The parotid has a lot of PSMA uptake when you do a PSMA PET scan, if you have a look at the PSMA PET, the parotids and submandibular is all right up and if you use that as a relative uptake and compare it to the tumor, it’s higher than liver, and if you use patients using the parotid as a baseline and said we want to choose patients that are more than the parotid, then guess what? These are very enriched for PSMA expression and you get a better response rate.

I think one of the things we’re finding out is that if you got more PSMA expression, you’re more likely to respond to the PSMA lutetium-177. It’s intuitively obvious. We’re still debating on what’s optimal and how we ought to do this going forward.

I think the FDA is going to give the VISION criteria for a PSMA uptake metastasis greater than liver, but we’re not through defining what’s optimal and what’s best for these patients.

Dr. George:

Absolutely, Oliver, they’re great points. And I think it’s one of the things that we’re really awaiting the rollout of this drug is how that’s going to translate into practice. Because as we’ve seen in a lot of imaging criteria, say, RECIST criteria, it doesn’t necessarily translate into practice.

Watch part two of the roundtable segment to hear Dr. Sprenkle’s experience with PSMA PET scans.

In additional segments, the panel discusses palliative benefits of lutetium-177-PSMA, if lutetium-177 is perfect, the limitations and advantages of lutetium-177-PSMA, and additional PSMA therapies being studied.