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Novel Prostate Cancer Biomarkers

Panelists:Raoul S. Concepcion, MD, FACS, Urology Associates; Michael D. Fabrizio, MD, FACS, Eastern Virginia Medical School; Jorge A. Garcia, MD, FACP, Taussig Cancer Institute; Judd W. Moul, MD, FACS, Duke University Medical Center; Charles J. Ryan, MD, UCSF Helen Diller Family Comprehensive Cancer Center
Published: Wednesday, Dec 16, 2015



Transcript:

Raoul S. Concepcion, MD, FACS: Are there any other technologies besides Circulating Tumor Cells (CTCs) that people are looking at in terms of a liquid biomarker, or liquid biopsy?

Charles J. Ryan, MD: This is a huge area right now for early biotechnology companies and large companies looking at this. Circulating, cell-free DNA is something that is in the works. It’s not quite tuned to the point that we can detect a splice variant because that’s a splicing variant and not so much a DNA mutation. Circulating tumor cells remain commercially available but mostly for enumeration.

he ARV7 would be the first qualitative assessment of circulating tumor cells that would be useful. And then there are a whole number of other companies out there that are seeking to exploit the genomics or protein expression in circulating tumor cells. But, like I said, some patients don’t have circulating tumor cells.

Raoul S. Concepcion, MD, FACS: I think it’s important that everybody remember that this is just one of many variants that can happen in the androgen receptor (AR). So, Judd, you’ve got a very highly functioning multidisciplinary clinic at Duke. You’re representing the urology side. You’ve got Andy and Dan over there on the GU side.

So how do you think this is going? Assuming that this comes to fruition and this is something that is going to be commercially available, how do you think that this is going to impact practice at your multidisciplinary clinic? What’s the importance of this long-term?

Judd W. Moul, MD, FACS: That’s a great question. I think that certainly this is one of the first examples of truly personalized medicine that could come to the forefront in castrate-resistant prostate cancer. As a urologist thinking historically, I think a lot of us might be freaked out about this. It’s hardcore molecular biology. How are they going to remember this? Is it something that’s going to affect their practice? But we’ve known about resistance to hormonal therapy since Huggins’ time in the 1940s.

I can remember when we were in training, the flutamide withdrawal syndrome came out and everyone was hot about AR mutations. But I guess that was a little bit ahead of its time because we couldn’t really figure out how to apply that clinically. And I guess putting my skeptic’s hat on, is this going to be flutamide withdrawal number 2 where it was a cool molecular concept that never really came to pass.

Final point for us as urologists, is that we’re mostly in the space of M0 CRPC and one of the questions that I was going to ask you guys is whether, like an M0 CRPC, can you actually circulating tumor cells? And if we start pulling the trigger for the oral agents even earlier, how will this come into play?

So I’m asking more questions than I’m answering, but, again, in the multidisciplinary clinic at Duke, we’re very proud of the effort but sometimes we still have challenges in the pass off between when is it a urology patient and then when does it transition to medical oncology. We try to play well in the sandbox but that’s one of the questions we have.

Raoul S. Concepcion, MD, FACS: Now, Mike, we were talking earlier before we started about a trial that’s currently underway where it is a novel molecule, galeterone, and, as part of this trial, there was the co-development of the companion diagnostic looking for the splice variant. I know you guys are involved in that trial. Give us some update, a little bit in terms of what you’ve seen so far.

Michael Fabrizio, MD, FACS: As you know, there’s probably only been about 40 or 50 patients. We don’t have a lot of experience with the drug, but I think the drug, potentially galeterone, is very unique in the fact that it has several mechanisms of action with inhibition of receptor and maybe a weak lyase inhibitor as well. So I think it potentially provides some opportunity for us to provide personalized treatment.

I think the results are pending, but it is exciting. We wouldn’t have been having this conversation three or four years ago with prostate cancer. And seven or eight years ago, none of these conversations we’re about to have would actually have occurred. It’s hormones and receptor blocker and that’s it, and now we have a variety of different things. So I think this trial is very exciting but we’ll have to wait.

Raoul S. Concepcion, MD, FACS: I think if you would have told me five or six years ago that I had to have a working knowledge of the androgen receptor as a urologist in independent community practice in order to manage my patients with prostate cancer, I would have said you were completely out of your mind. I think it’s going to be critical for all urologists.

Whether you’re involved in a multidisciplinary clinic, whether you’re in independent practice, small practice, or large practice, I think to better take care of these advancing prostate cancer patients is going to be critical.
                                                                                                                                                                                                                                                                                                       

Transcript Edited for Clarity

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Transcript:

Raoul S. Concepcion, MD, FACS: Are there any other technologies besides Circulating Tumor Cells (CTCs) that people are looking at in terms of a liquid biomarker, or liquid biopsy?

Charles J. Ryan, MD: This is a huge area right now for early biotechnology companies and large companies looking at this. Circulating, cell-free DNA is something that is in the works. It’s not quite tuned to the point that we can detect a splice variant because that’s a splicing variant and not so much a DNA mutation. Circulating tumor cells remain commercially available but mostly for enumeration.

he ARV7 would be the first qualitative assessment of circulating tumor cells that would be useful. And then there are a whole number of other companies out there that are seeking to exploit the genomics or protein expression in circulating tumor cells. But, like I said, some patients don’t have circulating tumor cells.

Raoul S. Concepcion, MD, FACS: I think it’s important that everybody remember that this is just one of many variants that can happen in the androgen receptor (AR). So, Judd, you’ve got a very highly functioning multidisciplinary clinic at Duke. You’re representing the urology side. You’ve got Andy and Dan over there on the GU side.

So how do you think this is going? Assuming that this comes to fruition and this is something that is going to be commercially available, how do you think that this is going to impact practice at your multidisciplinary clinic? What’s the importance of this long-term?

Judd W. Moul, MD, FACS: That’s a great question. I think that certainly this is one of the first examples of truly personalized medicine that could come to the forefront in castrate-resistant prostate cancer. As a urologist thinking historically, I think a lot of us might be freaked out about this. It’s hardcore molecular biology. How are they going to remember this? Is it something that’s going to affect their practice? But we’ve known about resistance to hormonal therapy since Huggins’ time in the 1940s.

I can remember when we were in training, the flutamide withdrawal syndrome came out and everyone was hot about AR mutations. But I guess that was a little bit ahead of its time because we couldn’t really figure out how to apply that clinically. And I guess putting my skeptic’s hat on, is this going to be flutamide withdrawal number 2 where it was a cool molecular concept that never really came to pass.

Final point for us as urologists, is that we’re mostly in the space of M0 CRPC and one of the questions that I was going to ask you guys is whether, like an M0 CRPC, can you actually circulating tumor cells? And if we start pulling the trigger for the oral agents even earlier, how will this come into play?

So I’m asking more questions than I’m answering, but, again, in the multidisciplinary clinic at Duke, we’re very proud of the effort but sometimes we still have challenges in the pass off between when is it a urology patient and then when does it transition to medical oncology. We try to play well in the sandbox but that’s one of the questions we have.

Raoul S. Concepcion, MD, FACS: Now, Mike, we were talking earlier before we started about a trial that’s currently underway where it is a novel molecule, galeterone, and, as part of this trial, there was the co-development of the companion diagnostic looking for the splice variant. I know you guys are involved in that trial. Give us some update, a little bit in terms of what you’ve seen so far.

Michael Fabrizio, MD, FACS: As you know, there’s probably only been about 40 or 50 patients. We don’t have a lot of experience with the drug, but I think the drug, potentially galeterone, is very unique in the fact that it has several mechanisms of action with inhibition of receptor and maybe a weak lyase inhibitor as well. So I think it potentially provides some opportunity for us to provide personalized treatment.

I think the results are pending, but it is exciting. We wouldn’t have been having this conversation three or four years ago with prostate cancer. And seven or eight years ago, none of these conversations we’re about to have would actually have occurred. It’s hormones and receptor blocker and that’s it, and now we have a variety of different things. So I think this trial is very exciting but we’ll have to wait.

Raoul S. Concepcion, MD, FACS: I think if you would have told me five or six years ago that I had to have a working knowledge of the androgen receptor as a urologist in independent community practice in order to manage my patients with prostate cancer, I would have said you were completely out of your mind. I think it’s going to be critical for all urologists.

Whether you’re involved in a multidisciplinary clinic, whether you’re in independent practice, small practice, or large practice, I think to better take care of these advancing prostate cancer patients is going to be critical.
                                                                                                                                                                                                                                                                                                       

Transcript Edited for Clarity
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Clinical Vignette Series: 34th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow®Feb 28, 20182.0
Community Practice Connections™: Personalized Sequencing in Castration-Resistant Prostate Cancer: Bridging the Latest Evidence to the Bedside in Clinical ManagementAug 25, 20181.5
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