ASCO 2019: Concurrent or Layered Treatment with Radium-223 and Enzalutamide or Abiraterone plus Prednisone/Prednisolone: A Retrospective Study of Real-World Clinical Outcomes in Patients with mCRPC - Medical Oncologist Perspective

Chicago, IL ( Radium-223 is an alpha emitter which selectively targets bone metastases and has been shown to improve overall survival in men with metastatic castration-resistant prostate cancer (mCRPC). It is unknown if a combination approach with second generation androgen antagonists such as abiraterone or enzalutamide is safe or synergistic with radium-223. Prior data presented at ESMO 2018 showed that the addition of radium-223 to abiraterone did not improve symptomatic skeletal event-free survival and was also associated with an increased frequency of bone fractures, compared with placebo.1 This data was similar to retrospective data from the Flatiron prostate cancer registry which also showed a higher incidence of SREs with concurrent treatment.This abstract provides further evidence regarding the safety of concurrent or layered treatment with radium-223 (Ra-223) and enzalutamide (Enza) or abiraterone plus prednisone/prednisolone (Abi/pred).
This abstract provides data on 625 patients who were treated with radium-223 in the United States from 2013 to 2017, based on a Flatiron prostate cancer registry. Baseline characteristics are shown below. 48% of patients received abiraterone or enzalutamide either concurrently or layered with radium. Concurrent treatment was defined as started within 30 days of each other, and layered treatment was started more than 30 days of each other. Layered therapy (73%) was more common than concurrent therapy (27%). 

The median time to initiation of radium from the diagnosis of CRPC was 11 months. 55% of all patients had prior therapy to radium and 55% of patients had concomitant bone health agents. Prior to radium, half of the patients had a prior symptomatic skeletal event and 18% of patients had previously had a pathologic fracture. 

Following treatment with radium, 27% of all patients had a symptomatic skeletal event, with 10% of patients experiencing pathologic fractures. The median OS from mCRPC was 28.1 months in the cohort. Taking into account that the median time from CRPC to radium was 11 months, the overall median OS after starting radium was 17 months, which is similar to what was found in ALSYMPCA, the registration trial of radium 223.3 The percentage of SSEs ranged from 20%-36% between the four different treatment groups (concurrent abi/radium, concurrent enza/radium, layered abi/radium, layered enza/radium). 
This abstract showed that 9-12% of patients treated with the combination of enzalutamide or abiraterone to radium 223 in a layered or concurrent fashion will experience a pathologic fracture. This is lower than the rate of fractures seen in ERA 223, where 29% of patients experienced fractures in the radium + abiraterone group and similar to the placebo group who received abiraterone alone (13%).1 One explanation of this difference could be that a higher proportion of patients in this trial were using a concomitant bone health agent (55%) compared with ERA 223 (40%). Of course, you cannot make cross-trial comparisons, and this was not a randomized study, so results must be treated cautiously as the authors suggest. There are several ongoing studies examining concurrent hormone/radium therapy, including PEACE III (NCT02194842), a randomized multicenter phase III trial comparing enzalutamide vs. a combination of Radium 223 and enzalutamide in asymptomatic or mildly symptomatic CRPC patients with metastases to the bone. 

Presented by: Neal Shore, MD, FACS, Board Certified Urologist, Medical Director of the Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC

Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA

  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 randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology 2019;20:408-19.
  2. George DJ, Sternberg CN, Sartor AO, et al. Clinical outcome with concurrent or layered treatment with radium-223 and abiraterone: A retrospective study of real-world experience with patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). American Society of Clinical Oncology; 2019.
  3. Parker C, Nilsson S, Heinrich D, et al. Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer. New England Journal of Medicine 2013;369:213-23.Parker C, Nilsson S, Heinrich D, et al. Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer. New England Journal of Medicine 2013;369:213-23.