Updated Data on Use of LuPSMA for Metastatic Prostate Cancer

Dr. Sartor: I'm here today to talk initially about some of the recent data presented on PSMA-617–lutetium-177. I'm going to refer to that just as PSMA lutetium 177, but it's going to be specific to the PSMA 617, which is now FDA approved. There were three presentations at ASCO.

First presentation: Update on therapy

The first was in the oral abstract session presented by Dr. Michael Hoffman. It was an update on the TheraP trial that compared, in the third-line setting, the cabazitaxel and the PSMA lutetium and the punchline is that there was no difference when it came to overall survival. Now, this was not designed as a non-inferiority study. And in fact it was randomized phase two, not a phase three. But when you look at the curves on the Kaplan-Meier plot for overall survival, it would be extremely difficult to conclude that there was any real differences.

Now, this was a surprise to some people because the PSMA lutetium had better PSA decline rates. And according to Dr. Hoffman, there was improvements in the progression-free survival, but no difference in the overall survival. A couple of important issues. Number one, cabazitaxel is a real drug. It's been FDA approved since the TROPIC trial compared to mitoxantrone showed an improvement in overall survival with cabazitaxel, and it also has been shown in the CARD trial to prolong overall survival relative to a second androgen receptor axis-targeted agent. So, cabazitaxel is a good drug and you don't appreciate necessarily how good it is when you simply look at PSA decline rates.

Now, the authors, Dr. Hoffman in particular, made statements that PSMA lutetium is preferable because of better adverse event rate. And I think that that could be true, but I don't necessarily think that it's absolutely true. I think there'll be cases where the cabazitaxel may be an appropriate treatment of choice in this post-docetaxel setting. And I think there'll be times when the PSMA lutetium-177 will be an appropriate choice. Both are active drugs, both have been shown to prolong survival, and both are important. And I think that's the conclusion I would draw. There were two other PSMA lutetium abstracts presented at ASCO.

Second presentation: Effect of therapies

One was looking at the effect of concurrent therapies and prior therapies on the outcomes of the VISION trial, and the VISION trial was the trial that looked at PSMA lutetium in comparison to standard of care, with most of the standard of care being a second-line hormone, or maybe even a third-line hormonal agent.

And basically, what they found is that it really didn't make a lot of difference about what your prior treatments were, that the PSMA lutetium was a more effective therapy than the control group. I'll simply say that it was interesting to me that when you looked at the concomitant therapies, that those individuals who had an AR axis-targeted agent, typically either enzalutamide or abiraterone, seemed to fare better. And that was true, not only in the control group, but also in the group of the PSMA lutetium treated patients. And there has been discussion about the up-regulation of the PSMA target with antigen axis-targeted drugs, provocative, but not definitive. Bottom line is VISION trial is positive.

Third presentation: PSMA imaging

In the next analysis, there was an analysis of the PSMA PET imaging and correlates with outcomes in the VISION trial. What they found was that those individuals with the highest PSMA, total uptake, ended up doing the best, and that was in terms of overall survival. Divided it into quartiles, highest PSMA, total body uptake. Second, third, and fourth highest. The best uptake had the best survival. The bottom three quartiles for survival were actually pretty similar.

When they looked at rPFS, which was an additional endpoint used invasion, there was a little more best in the highest quartile PSMA uptake and a little more of a stair effect going down to the lowest. But the interesting thing to me is that overall survival, the patients with the highest PSMA PET uptake, they did very well. The patients with lower were not that much distinct between the second, third, and fourth quartiles. So, we know a little bit more about PSMA lutetium therapy today. We know a little bit more about cabazitaxel. We know a little bit more about prior therapies and concomitant therapies. We know a little bit more about PSMA PET uptake as a predictive for outcomes. I thought these were interesting findings and all presented at ASCO 2022.