Select Topic:
Browse by Series:

Ideal Timing of Radium-223 While Treating CRPC

Insights From: Evan Yu, MD, University of Washington; Ulka Vaishampayan, MD, Barbara Ann Karmanos Cancer Institute ; Neeraj Agarwal, MD, Huntsman Cancer Institute
Published: Tuesday, Dec 11, 2018



Transcript: 

Evan Yu, MD: The term therapeutic layering is new, but the concept is actually old. We talk about combination therapy or starting a couple of different therapies together. Therapeutic layering is if you’re on one agent already and you add another agent on top. If you think about it, prostate cancer is a perfect example where therapeutic layering is commonly done. A patient can’t develop castration-resistant prostate cancer without progressive disease while on standard androgen deprivation therapy. When someone develops castration-resistant prostate cancer, they chronically remain on their LHRH [luteinizing hormone-releasing hormone] therapy for life. Whatever else you add on is therapeutic layering.

Now, this term became more popular recently as physicians and providers are using radium-223 and layered on top of drugs like abiraterone and enzalutamide. There are no data to show that it’s the right approach, and no data to show that it’s the wrong approach. There are obviously some data with ERA 223 trial right now that has individuals concerned about fractures and deaths with the combination of radium and abiraterone. But keep in mind those were combinations started together—it wasn’t layering. We have yet to see data from the PEACE trial, where we’ll see combination data with radium-223 and enzalutamide. Again, therapeutic layering is just adding one agent on top of another, and there is outstanding long-term precedence of that with adding agents in castration-resistant prostate cancer on top of LHRH therapy. But in going to the next level, we’ll have to wait and see. There’s not a lot of trials that are addressing that.

Neeraj Agarwal, MD: Radium-223 was approved based on a randomized phase III trial where inclusion criteria included patients who had disease progression on docetaxel chemotherapy or who could not tolerate docetaxel or who refused to be on docetaxel chemotherapy. Based on these criteria, I use radium in those patients who have either progressed on, cannot tolerate, or have refused docetaxel. In my practice, for a patient who has bone metastasis in castrate-resistant metastatic prostate cancer setting and has bone pain, I would use radium.

Ulka Vaishampayan, MD: Administration of radium following chemotherapy is fairly standard. There are adequate safety and efficacy data, especially because the registration trial—the ALSYMPCA trial—included those patients. About half of the patients on the ALSYMPCA trial were post-docetaxel therapy, so they had already received chemotherapy, showed signs of progression, and were enrolled in the study. Following radium-223, regarding whether to give chemotherapy and whether there are increased adverse events, so far all of the experience that has been reported on this has shown that there is no increased incidence of adverse events found in using chemotherapy after radium-223. Even on the ALSYMPCA trial, about 17% of patients went on to get chemotherapy and there were no adverse events reported.

Radium-223 was evaluated initially in the ALSYMPCA trial in comparison to placebo. This was a double-blind randomized trial. The maximum number of doses chosen for that study was 6 for radium-223. Since then, there have been studies looking at randomizing patients to receive the standard dose versus a longer time period of up to 12 doses or a higher dose of radium-223. That study, however, showed that the higher dose or the longer duration did not seem to add anything to patient outcomes. At this time, it cannot be recommended to extend the treatment beyond 6 doses.

Transcript Edited for Clarity 
Slider Left
Slider Right


Transcript: 

Evan Yu, MD: The term therapeutic layering is new, but the concept is actually old. We talk about combination therapy or starting a couple of different therapies together. Therapeutic layering is if you’re on one agent already and you add another agent on top. If you think about it, prostate cancer is a perfect example where therapeutic layering is commonly done. A patient can’t develop castration-resistant prostate cancer without progressive disease while on standard androgen deprivation therapy. When someone develops castration-resistant prostate cancer, they chronically remain on their LHRH [luteinizing hormone-releasing hormone] therapy for life. Whatever else you add on is therapeutic layering.

Now, this term became more popular recently as physicians and providers are using radium-223 and layered on top of drugs like abiraterone and enzalutamide. There are no data to show that it’s the right approach, and no data to show that it’s the wrong approach. There are obviously some data with ERA 223 trial right now that has individuals concerned about fractures and deaths with the combination of radium and abiraterone. But keep in mind those were combinations started together—it wasn’t layering. We have yet to see data from the PEACE trial, where we’ll see combination data with radium-223 and enzalutamide. Again, therapeutic layering is just adding one agent on top of another, and there is outstanding long-term precedence of that with adding agents in castration-resistant prostate cancer on top of LHRH therapy. But in going to the next level, we’ll have to wait and see. There’s not a lot of trials that are addressing that.

Neeraj Agarwal, MD: Radium-223 was approved based on a randomized phase III trial where inclusion criteria included patients who had disease progression on docetaxel chemotherapy or who could not tolerate docetaxel or who refused to be on docetaxel chemotherapy. Based on these criteria, I use radium in those patients who have either progressed on, cannot tolerate, or have refused docetaxel. In my practice, for a patient who has bone metastasis in castrate-resistant metastatic prostate cancer setting and has bone pain, I would use radium.

Ulka Vaishampayan, MD: Administration of radium following chemotherapy is fairly standard. There are adequate safety and efficacy data, especially because the registration trial—the ALSYMPCA trial—included those patients. About half of the patients on the ALSYMPCA trial were post-docetaxel therapy, so they had already received chemotherapy, showed signs of progression, and were enrolled in the study. Following radium-223, regarding whether to give chemotherapy and whether there are increased adverse events, so far all of the experience that has been reported on this has shown that there is no increased incidence of adverse events found in using chemotherapy after radium-223. Even on the ALSYMPCA trial, about 17% of patients went on to get chemotherapy and there were no adverse events reported.

Radium-223 was evaluated initially in the ALSYMPCA trial in comparison to placebo. This was a double-blind randomized trial. The maximum number of doses chosen for that study was 6 for radium-223. Since then, there have been studies looking at randomizing patients to receive the standard dose versus a longer time period of up to 12 doses or a higher dose of radium-223. That study, however, showed that the higher dose or the longer duration did not seem to add anything to patient outcomes. At this time, it cannot be recommended to extend the treatment beyond 6 doses.

Transcript Edited for Clarity 
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
35th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow® Clinical Vignette SeriesJan 31, 20192.0
Oncology Briefings™: Current Perspectives on Preventing and Managing Tumor Lysis SyndromeJun 30, 20191.0
Publication Bottom Border
Border Publication
x