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Combining Radium-223 With Other Therapies in Prostate Cancer

Panelists:Raoul S. Concepcion, MD, FACS, Urology Associates; Michael S. Cookson, MD, MMHC, University of Oklahoma Health Sciences Center; Daniel P. Petrylak, MD, Yale School of Medicine; Daniel I. Quinn, MBBS, PhD, FRACP, FACP, University of Southern California; Neal D. Shore, MD, FACS, Carolina Urologic Research Center; Charles J. Ryan, MD, UCSF Helen Diller Family Comprehensive Cancer Center
Published: Monday, Jun 20, 2016


Transcript:

Raoul S. Concepcion, MD:
Neal, dovetail on what David was saying. You’ve reported on some use of concomitant radium and abiraterone.

Neal D. Shore, MD: So, this is an interesting fellow. This is a relatively young man who has highly aggressive disease and he received his sipuleucel-T, and then there was kind of a delay for his next line of therapy. In my clinic, I would have almost invariably, within a fairly short period of time, started him on one of the novel hormonal lines of therapy, either abiraterone or enzalutamide. And, in my experience, what typically happens is that for the vast majority of patients, we see those PSA (prostate-specific antigen) declines. But then, invariably, the PSA starts to come up, and somehow describe this as now some evidence of a biologic progression. There’s perhaps mutational events happening, and then there’s a lag period. And, invariably, there will be radiographic progression (if you’re following the patient close enough), and eventually more symptomatology.

In the study that we did—and we reported it now at ASCO GU and at AUA—we combined abiraterone and radium-223 concomitantly, and we started our investigator-initiated trial before there was even any evidence from the expanded access program. So, the bottom line is that combining abiraterone and radium-223 does not change the safety profile or the toxicity events. They’re still there, what you would expect to see if giving it as monotherapy. And we’ve actually reported that the majority of our patients have had FACT-P (Functional Assessment of Cancer Therapy-Prostate) subset improvement in their quality of life, lowering in their pain tolerance as well. BPI (brief pain inventory) was measured as well and that also decreased.

It’s not true for all patients, depending upon where you start them. So, I’m actually in more of the mindset to be more aggressive in combining the therapies together. In the ALSYMPCA trial, the best standard of care combined radium with ketoconazole, which is an androgen biosynthesis inhibitor, and the earlier generation lutamides—bicalutamide, nilutamide, flutamide—steroids, estrogens, and focal radiation. I actually am very aggressive in combining therapy and not going step by step because, as was mentioned, I want to get in the full six cycles and have the ability to give chemotherapy when it’s appropriate.

Raoul S. Concepcion, MD: Mike, your point was well taken, that there are these windows and these windows seem to close pretty quickly. And I think we have to hit that opportunity. The one patient that really bothers me is the elderly 78-year-old, 80-year-old with multiple bone metastasis, no soft tissue disease, and he is truly asymptomatic. And, to me, he is a walking time bomb. And, of course, that’s not the indication to give radium-223. Didn’t the European early-access program report on some of those patients?

Daniel P. Petrylak, MD: You mean combining with abiraterone?

Raoul S. Concepcion, MD: Yes.

Daniel P. Petrylak, MD: It did seem that there was a survival benefit. Those patients did seem to do better than either drug alone. So, I think that’s a very interesting observation. We have a trial that compares abiraterone plus radium to enzalutamide plus radium to radium alone, as far as radiographic progression-free survival is concerned, that that will hopefully read out later this year. That may give us a little bit more information about what the role of these other agents are in combination with radium. But, getting back to Dave’s point, the data suggests that you really need the full six doses to get a survival benefit. So, what I would tend to do in a patient where they develop visceral disease, is treat them at that particular point with chemotherapy. If I get a really good response, then I’ll finish it up with radium after that. That may be a way of selecting those patients who are going to do better.

Transcript Edited for Clarity
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Transcript:

Raoul S. Concepcion, MD:
Neal, dovetail on what David was saying. You’ve reported on some use of concomitant radium and abiraterone.

Neal D. Shore, MD: So, this is an interesting fellow. This is a relatively young man who has highly aggressive disease and he received his sipuleucel-T, and then there was kind of a delay for his next line of therapy. In my clinic, I would have almost invariably, within a fairly short period of time, started him on one of the novel hormonal lines of therapy, either abiraterone or enzalutamide. And, in my experience, what typically happens is that for the vast majority of patients, we see those PSA (prostate-specific antigen) declines. But then, invariably, the PSA starts to come up, and somehow describe this as now some evidence of a biologic progression. There’s perhaps mutational events happening, and then there’s a lag period. And, invariably, there will be radiographic progression (if you’re following the patient close enough), and eventually more symptomatology.

In the study that we did—and we reported it now at ASCO GU and at AUA—we combined abiraterone and radium-223 concomitantly, and we started our investigator-initiated trial before there was even any evidence from the expanded access program. So, the bottom line is that combining abiraterone and radium-223 does not change the safety profile or the toxicity events. They’re still there, what you would expect to see if giving it as monotherapy. And we’ve actually reported that the majority of our patients have had FACT-P (Functional Assessment of Cancer Therapy-Prostate) subset improvement in their quality of life, lowering in their pain tolerance as well. BPI (brief pain inventory) was measured as well and that also decreased.

It’s not true for all patients, depending upon where you start them. So, I’m actually in more of the mindset to be more aggressive in combining the therapies together. In the ALSYMPCA trial, the best standard of care combined radium with ketoconazole, which is an androgen biosynthesis inhibitor, and the earlier generation lutamides—bicalutamide, nilutamide, flutamide—steroids, estrogens, and focal radiation. I actually am very aggressive in combining therapy and not going step by step because, as was mentioned, I want to get in the full six cycles and have the ability to give chemotherapy when it’s appropriate.

Raoul S. Concepcion, MD: Mike, your point was well taken, that there are these windows and these windows seem to close pretty quickly. And I think we have to hit that opportunity. The one patient that really bothers me is the elderly 78-year-old, 80-year-old with multiple bone metastasis, no soft tissue disease, and he is truly asymptomatic. And, to me, he is a walking time bomb. And, of course, that’s not the indication to give radium-223. Didn’t the European early-access program report on some of those patients?

Daniel P. Petrylak, MD: You mean combining with abiraterone?

Raoul S. Concepcion, MD: Yes.

Daniel P. Petrylak, MD: It did seem that there was a survival benefit. Those patients did seem to do better than either drug alone. So, I think that’s a very interesting observation. We have a trial that compares abiraterone plus radium to enzalutamide plus radium to radium alone, as far as radiographic progression-free survival is concerned, that that will hopefully read out later this year. That may give us a little bit more information about what the role of these other agents are in combination with radium. But, getting back to Dave’s point, the data suggests that you really need the full six doses to get a survival benefit. So, what I would tend to do in a patient where they develop visceral disease, is treat them at that particular point with chemotherapy. If I get a really good response, then I’ll finish it up with radium after that. That may be a way of selecting those patients who are going to do better.

Transcript Edited for Clarity
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