GU Oncology Now, recently spoke with Dr. Jeremie Calais, Director, Clinical Research Program, Ahmanson Translational Theranostics Division of the Department of Molecular and Medical Pharmacology at UCLA. Dr. Calais discussed imaging-based precision medicine in prostate cancer, and more specifically, PET imaging-based precision medicine. See what Dr. Calais had to say.

GU Oncology Now: Can you provide us with some background on yourself and your specialty?

Dr. Jeremie Calais: Sure. I’m a nuclear medicine physician. I was trained in France. I joined the UCLA theranostic division five years ago, and now I’m leading the clinical research program of the theranostics division. So theranostics now, the research is a lot about PSMA. There are other targets as well, but we work a lot on PSMA targeted theranostics in the past five years.

How big an impact has precision medicine had on prostate oncology?

Precision medicine is a term that encompasses many, many different things in fact. It can go from imaging-based precision medicine, but you’ll have many others with the genetic, with the, some blood tests, or AI. You can put any parameters for precision.

I’m going to talk only about imaging-based precision medicine and more even specifically PET imaging-based precision medicine. That’s what I do, because you can also use other imaging techniques to do other types of precision medicine. So let’s talk about PET imaging in prostate cancer and how it can help prostate cancer patients and prostate cancer doctors.

Can you speak to us about a study you were involved in called the “Safety of PSMA-targeted molecular radioligand therapy with 117Lu-PSMA-617?”

So here it’s not about PETs, it’s more about treatments. So theranostics or the combination of imaging and therapy aiming for the same molecular target, which is here PSMA. These studies you’re referring to are the reports of PSMA-targeted molecular radiotherapy of our cohorts of patients treated here at UCLA.

It was prospective studies. We investigated two level of radioactivity injected of Lutetium PSMA. One was six gigabecquerel one was 7.4 gigabecquerel. We follow the patients for a couple of years. And then here in these studies, we report safety and efficacy in these two cohorts.

So it’s not really about a PET imaging here. It’s more about treatments targeting PSMA… Just briefly, if I have to talk about the results of the study, at the end, we showed that there was no real significant difference between six and 7.4 gigabecquerel. It was safe. The side effects and the toxicity profile was good. And let’s say manageable with a standard of care, a good medical oncology therapies, and each show very good antitumor effect as well. It seems that the more you see of just a response, the more it is coordinated with outcomes survival at the end. And there are studies that are much more bigger, such as the vision trial that show similar results with good antitumor effects and even good effects on the outcome of the patient over survival and a radiographic progression survival. So at the end, we did some PSMA is now a very, more than a promising treatments.

It’s started to be in the landscape, more and more established. I’m sure that in the next years it will become standard of care for these patient population, which is first chemotherapy in CRPC patients. And we see that more and more. It has a good safety profile, especially when you compare it to chemotherapy. And it has a good instrument efficacy, especially if you select better the patients. And, this can be transitioned to more precision medicine using imaging.

The way we should select patients or how, if we should do or not selection based on PSMA pet imaging for these treatments. This is where we can talk a little bit of more precision medicine.

What are some of the advantages and challenges of using PSMA PET?

Yes. let’s have an overview of what is the current practice as of now, usually we say patient is eligible to receive PSMA targeted molecular therapy. If the PSMA pet is positive and has some kind of Broad criteria. So In VISION, it was uptake of the PSMA signal above the liver and no lesion that you could see on the CT without PSMA uptake or uptake below the liver. In the Australian trials, they use a Juul, a tracer approach, including FTG pets, which allows to detect more PSMA negative lesions, FDG pet is the B quality pet tracer. So it would show Highly good to teach mostly aggressive regions. And then you can combine that maybe CT or MRI would not have shown, and you can combine it with PSMA PET and you can see if it match. If you have but then, the same thing, lesions, PSMA negative that you see on AVG bets,

They were excluded as well. So at the end in vision, they defined PSMA negative regions using conventional imaging and in the therapy trial or the Australian trial, they define PSMA negative lesions using conventional imaging and also FTG pets. So they excluded more patients. Well, that’s one thing. It’s how you define this criteria to select patient for the therapy. There are multiple layers of understanding here, because of course the better you select the patients patient with very high uptake, low tumor volume, no FDG lesions, no PSMA negative lesions. They will probably respond better than the others. So you can have better response rates, but it doesn’t answer the question of what you do with the others. And should we treat them or not? Because you can still have a pretty good effect, even in patients that are considered either PSMA negative by imaging.

So all these thresholds, the way you play with it, it really impacts your survival outcomes but it doesn’t really- there is no yet good treatment algorithm for defining this. So I think this will come the more and more patients are being treated with therapy. And the more we be able to analyze the imaging baseline characteristics of these patients, and try to identify cohorts of very good responders or very poor responders, and maybe in the future, we will do prospective trials using the PSMA pet patterns in the PSMA pets different criteria to do different types of therapy and see if there is really prospectively a difference between these patients. But as of now, this is a bit early and, but the mature data will come in the future.

Do you believe that in order to enhance PSMA imaging that enhanced algorithms are needed?

Yes. So, these technology are still new. The VISION trial is very good. It was made for registration purposes and approval of the FDA, it’s robust data, it’s a very valuable data. There are other data. For example, in Cornell, in New York, they treated some patients even with PSMA negative stats. So there is a little bit of small cohorts reported with PSMA negative score initially treated with PSMA targeted therapy and there is a little bit of outcome that, that there. As expected, and let’s say, hopefully, the outcome of this patient is worse than the one that were highly positive, which shows that, of course the more uptake you’ll have on PSMA pet scan, the less number of PSMA negative lesion, the better the response to the therapy to the PSMA targeted therapy, the better the response would be.

So that goes in line. Now I think again, mature data will come little by little. The more we do these studies, it is important also it will be important also to have some data in PSMA negative patients. And one other improvement we could do in that space is to have automatic tools. Density is a whole body imaging modality.

Usually, when we say SUV, we talk about SUV max so we will look at the highest updates in one of the lesion among all the lesions. And you can have very high indigeneity of the disease without a lesion with low updates, some lesion with a high uptake, and it should take just [inaudible]. You’re really not capturing the whole body disease burden. And why is that? It’s because when you do it a slice by slice, it takes time for the imaging reader to do all these assessments. And each you have to define what is diseased or not on the whole body level in very heavily metastasis patient. It takes a lot of time. So automatic tools where you would do one click, you will have the whole body tumor segment it’s that will give you the volume of the PSMA expressing disease that will give you the level of PSMA expression with SUV mean in the whole body.

So the average is UV and not only the max. That would give you maybe some even further definition of the amount of bone tumor volume, the amount of [inaudible] tumor volume. And with all these parameters on the one-click methods, this will help a lot to implement and use just PSMA PET parameters to define the prognostic of patient and maybe even to define some treatment ivory space on that. These tools are being developed by multiple either industry vendors or academic researchers. They are not yet ready for prime time. I hope it will come soon because that’s the only way really to use the PSMA PET information. These tools widely available and implemented.

Any closing thoughts?

I would love to be invited again because there will be many updates. This is a very dynamic field, a very dynamic topic. And let’s say every three to six months we have new reports. We learn every day. So I shall have new things to say in a very short time.