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Assessing Treatment Response in M0 CRPC

Panelists: Raoul S. Concepcion, MD, FACS, Comprehensive Prostate Center; Daniel George, MD, Duke Cancer Institute; Alec Koo, MD, Skyline Urology; Phillip Koo, MD, MD Anderson Cancer Center; Neal D. Shore, MD, FACS, Carolina Urologic Research Center
Published: Thursday, May 03, 2018



Transcript: 

Raoul S. Concepcion, MD, FACS: Are there trials looking at taxanes in this M0 space?

Neal D. Shore, MD, FACS: I’m not aware of any taxane, currently.

Daniel George, MD: There was a study that was done, sponsored by Sanofi, that looked at intermittent ADT plus or minus taxanes in the hormone-sensitive M0 space. It got stopped early, but it didn’t really have a dramatic signal. I think that there’s some controversy as to whether or not it’s as effective in this slower progressing population. But I think this really addresses the mechanism, that rapidly doubling time PSA is androgen receptor–driven. Both of these drugs directly target that. And when you look at the PSA response, as fantastic as the metastasis-free survival results are, the PSA progression-free survivals are even more dramatic. It really suggests that it’s an on-target biology that is driving this, and that these are the appropriate therapies, if you’re going to treat M0 castrate-resistant disease.

Neal D. Shore, MD, FACS: The majority of the patients were very high performing, in terms of their ECOG status. I do think that additional patient-reported outcomes data will demonstrate to be, when patients see that their PSA has gone down so low—which we all know is a concern, but may be more subjective and anxiety provoking—beneficial to patient-reported outcomes. We consider delaying other antineoplastic effects. And also, more importantly, some of the SPARTAN data were very good at demonstrating a delay in symptomatic skeletal events. So, a risk-benefit discussion has to occur with each patient. Clearly, somebody with a really slow doubling time and/or other comorbidities may not be the ideal person. But, as we know, as 80 becomes the new 60, and as many patients will die of metastatic disease, especially if they have good actuarial survival, I think these data are compelling.

Raoul S. Concepcion, MD, FACS: Phil, are there any abstracts that you know of? Or any trials looking at some of these newer biomolecular imaging techniques in this M0 space?

Phillip Koo, MD: No. Currently, no. I think there have been some small animal studies looking at fluciclovine in small mice that were castration resistant. I think that moving forward, this is a hot topic. Being able to use some of these advanced imaging tools as a biomarker to assess response is great. One of the strengths of PET/CT, which is what we’re talking about today, is the fact that it’s semi-quantitative. We use FDG PET/CT all the time for a lot of other solid tumors and hematologic malignancies, and we can assess response. We look at metabolic activity. We can provide quantitative parameters and really tailor the care. So, right now, this is sort of the baseline with regards to detecting metastases. But the next stage is going to be, how do we use imaging to help our referring physicians identify those patients who are responding versus those patients who aren’t? And then we can figure out when to change. PSA is a great marker, but we all know that PSA doesn’t always work. This imaging tool could potentially lead to that, and there are some small trials, single-site, again, that are talking about treatment response. But we need to look at it more systematically, at a higher level.

Raoul S. Concepcion, MD, FACS: I think you make a great point. I’m sure Dan would echo this. Urologists get lulled into this whole PSA effect. You can have lower PSAs and have progressive disease. We all know that there are so many resistance mechanisms that take out the androgen pathway. And so, now, all of a sudden, these are different genotypic tumors at this point.

Daniel George, MD: That’s correct. I’m going to be very interested in the maturation of this data. What we’re looking at, right now, is really the early half of these outcomes. The medians are very unstable. Most of the events haven’t hit the median. But when we follow this data out longer, we’re going to see a tail. We’re going to see, potentially, some patients who have no metastasis for 5, 7, 8 years, potentially. It will be interesting, going forward, to see if there’s a role for molecular imaging to help us identify who might be a long-term remission patient with a strategy like that. I think that’s going to be really helpful in understanding whether we are just delaying this process for a couple of years or if there is a subset of patients who we’re really having a more indefinite effect on by using this. Both of these drugs are very unique in the field. These patients may have been exposed to bicalutamide or other drugs, but their tumors have never seen the kind of biology of this. And, again, this is a different phenotype, as we’ve talked about, then the M1 castrate-resistant disease. So, even though we don’t necessarily see that many long-term responders there, because of this heterogeneity that you refer to, there may be a more enriched subset here that get that. That’s going to encourage us to figure out how it applies earlier.

Phillip Koo, MD: That’s an interesting point. We talk about using advanced imaging at biochemical recurrence more often, and that’s going to shrink the M0 space and make everyone M1. However, it also might help us identify those who are truly M0. Those patients might be the ones who fall in that tail. So, if we can work together and figure out how we incorporate imaging, that’s exactly what we’re going to do. And those patients, who can really benefit from this, with advanced imaging, are probably going to have better results—even greater than 2-years’ MFS.

Transcript Edited for Clarity

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Transcript: 

Raoul S. Concepcion, MD, FACS: Are there trials looking at taxanes in this M0 space?

Neal D. Shore, MD, FACS: I’m not aware of any taxane, currently.

Daniel George, MD: There was a study that was done, sponsored by Sanofi, that looked at intermittent ADT plus or minus taxanes in the hormone-sensitive M0 space. It got stopped early, but it didn’t really have a dramatic signal. I think that there’s some controversy as to whether or not it’s as effective in this slower progressing population. But I think this really addresses the mechanism, that rapidly doubling time PSA is androgen receptor–driven. Both of these drugs directly target that. And when you look at the PSA response, as fantastic as the metastasis-free survival results are, the PSA progression-free survivals are even more dramatic. It really suggests that it’s an on-target biology that is driving this, and that these are the appropriate therapies, if you’re going to treat M0 castrate-resistant disease.

Neal D. Shore, MD, FACS: The majority of the patients were very high performing, in terms of their ECOG status. I do think that additional patient-reported outcomes data will demonstrate to be, when patients see that their PSA has gone down so low—which we all know is a concern, but may be more subjective and anxiety provoking—beneficial to patient-reported outcomes. We consider delaying other antineoplastic effects. And also, more importantly, some of the SPARTAN data were very good at demonstrating a delay in symptomatic skeletal events. So, a risk-benefit discussion has to occur with each patient. Clearly, somebody with a really slow doubling time and/or other comorbidities may not be the ideal person. But, as we know, as 80 becomes the new 60, and as many patients will die of metastatic disease, especially if they have good actuarial survival, I think these data are compelling.

Raoul S. Concepcion, MD, FACS: Phil, are there any abstracts that you know of? Or any trials looking at some of these newer biomolecular imaging techniques in this M0 space?

Phillip Koo, MD: No. Currently, no. I think there have been some small animal studies looking at fluciclovine in small mice that were castration resistant. I think that moving forward, this is a hot topic. Being able to use some of these advanced imaging tools as a biomarker to assess response is great. One of the strengths of PET/CT, which is what we’re talking about today, is the fact that it’s semi-quantitative. We use FDG PET/CT all the time for a lot of other solid tumors and hematologic malignancies, and we can assess response. We look at metabolic activity. We can provide quantitative parameters and really tailor the care. So, right now, this is sort of the baseline with regards to detecting metastases. But the next stage is going to be, how do we use imaging to help our referring physicians identify those patients who are responding versus those patients who aren’t? And then we can figure out when to change. PSA is a great marker, but we all know that PSA doesn’t always work. This imaging tool could potentially lead to that, and there are some small trials, single-site, again, that are talking about treatment response. But we need to look at it more systematically, at a higher level.

Raoul S. Concepcion, MD, FACS: I think you make a great point. I’m sure Dan would echo this. Urologists get lulled into this whole PSA effect. You can have lower PSAs and have progressive disease. We all know that there are so many resistance mechanisms that take out the androgen pathway. And so, now, all of a sudden, these are different genotypic tumors at this point.

Daniel George, MD: That’s correct. I’m going to be very interested in the maturation of this data. What we’re looking at, right now, is really the early half of these outcomes. The medians are very unstable. Most of the events haven’t hit the median. But when we follow this data out longer, we’re going to see a tail. We’re going to see, potentially, some patients who have no metastasis for 5, 7, 8 years, potentially. It will be interesting, going forward, to see if there’s a role for molecular imaging to help us identify who might be a long-term remission patient with a strategy like that. I think that’s going to be really helpful in understanding whether we are just delaying this process for a couple of years or if there is a subset of patients who we’re really having a more indefinite effect on by using this. Both of these drugs are very unique in the field. These patients may have been exposed to bicalutamide or other drugs, but their tumors have never seen the kind of biology of this. And, again, this is a different phenotype, as we’ve talked about, then the M1 castrate-resistant disease. So, even though we don’t necessarily see that many long-term responders there, because of this heterogeneity that you refer to, there may be a more enriched subset here that get that. That’s going to encourage us to figure out how it applies earlier.

Phillip Koo, MD: That’s an interesting point. We talk about using advanced imaging at biochemical recurrence more often, and that’s going to shrink the M0 space and make everyone M1. However, it also might help us identify those who are truly M0. Those patients might be the ones who fall in that tail. So, if we can work together and figure out how we incorporate imaging, that’s exactly what we’re going to do. And those patients, who can really benefit from this, with advanced imaging, are probably going to have better results—even greater than 2-years’ MFS.

Transcript Edited for Clarity
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