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AUA 2019

AUA 2019: A Large Real World Cohort Evaluating Combination Therapy with Radium-223 and Abiraterone or Enzalutamide.

Chicago, IL (UroToday.com) Combination therapies for metastatic castration-resistant prostate cancer (mCRPC) are currently being investigated. The objective of this study presented at AUA 2019 was to use a large, real-world cohort to evaluate the risk of all-cause mortality (ACM) and skeletal-related events among men who received radium-223 with or without abiraterone/enzalutamide.

            For this study, charts were reviewed of all men with mCRPC in the entire Veterans Affairs (VA) system as of January 1st, 2013 who received radium-223. Cox models were used to test the association between concomitant radium-223 use with abiraterone/enzalutamide on ACM and skeletal-related event vs. radium-223 alone. In the analysis, four sensitivity analyses were done:

  • Men with >=30 days of treatment overlap
  • Men with >=60 days of overlap
  • Men who received intermittent radium, defined as less than an average of 0.8 infusions/month
  • Men stratified by use of denosumab/bisphosphonate at radium-223 start.
            There were 318 men that met inclusion criteria for this study, including 116 (37%) men taking abiraterone or enzalutamide at the same time as radium-223. On univariable and multivariable analysis, there was no significant difference in ACM between men who did and did not receive abiraterone/enzalutamide while on radium-223 (p=0.33). Similarly, there was no difference in time to skeletal-related event in men on concomitant abiraterone/enzalutamide (p=0.88). Additionally, there was no difference in ACM for any of the sensitivity analyses, but there was a trend to increased skeletal-related event risk in men who had >=30 days of therapy overlap (p=0.051) and men who received radium at regular intervals (p=0.064). There was no association with ACM or SRE after stratifying by use of denosumab /bisphosphonates.


AUA2019_Combination Therapy with Radium-223 .png

Despite surveying the VA national database, the main limitation of this study was the small sample size comprising men that received concomitant radium-223 and abiraterone/enzalutamide. Despite these limitations, the study suggests that the ominous findings in ERA-223 may not be generalizable.

Dr. Zhao concluded with several take-home messages:

  • There was no increased ACM risk among patients receiving radium 223 with abiraterone or enzalutamide
  • There was a trend to increased skeletal-related event risk in some subgroups, but this was not significant.
  • Further work needs to evaluate the optimal sequence and timing of combination therapies with a focus on the safety profile.
 

Presented by: Hanson Zhao, Urology Resident, Cedars-Sinai Medical Center, Los Angeles, California
Co-authors: Lauren Howard, Amanda De Hoedt, Durham, NC, Martha Terris, Augusta, GA, Christopher Amling, Portland, OR, Christopher Kane, La Jolla, CA, Matthew Cooperberg, San Francisco, CA, William Aronson, Los Angeles, CA, Thomas Polascik, Durham, NC, Stephen Freedland, Los Angeles, CA

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University - Medical College of Georgia, Twitter: @zklaassen_md 
References:
  1. Smith M, Parker C, Saad F, et al. Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): A randomized, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2019 Mar;20(3):408-419.