Advertisement

Lower Fracture Rates in Patients Treated with Radium-223, Abiraterone or Enzalutamide, When Given Concurrently with Bone Health Agents: A Real-World Analysis

Published:April 27, 2022DOI:https://doi.org/10.1016/j.clgc.2022.04.015

      Highlights

      • 93% of 177 patients on Radium-223, abiraterone or enzalutamide, had bone health agent
      • 11 of our patients on both bone health agent and Radium-223 had a fracture, 6.2%
      • Only 41% of the ERA223 study cohort received a bone health agent
      • Our cohort had comparatively fewer skeletal related events than ERA223 study, 29%

      Abstract

      Background

      The phase 3 trial ERA223 demonstrated an increased fracture rate and no survival advantage for metastatic castration resistant prostate cancer (mCRPC) patients on Radium-223 (Ra-223) with abiraterone, leading to regulatory restrictions on combination therapy. However, less than half of trial patients received bone health agents (BHA). We reviewed electronic health record (EHR) data evaluating fracture rates for patients on BHA receiving Ra-223, androgen deprivation therapy and either abiraterone or enzalutamide.

      Patients and Methods

      We conducted a retrospective, cohort analysis of EHR data of mCRPC patients on Ra-223 treated at a single community center by a single provider between 2010 and 2018. The primary objective was evaluating fracture rates for patients on BHA receiving Ra-223 and abiraterone. We conducted a secondary analysis for enzalutamide.

      Results

      One hundred seventy-seven patients received Ra-223 concurrently with abiraterone or enzalutamide between November 2010 and August 2018. The median age was 73 at first Ra-223 dose (range 40-93). The median follow-up time from last Ra-223 dose was 30 months (range 2-106). One hundred sixty-four patients (93%) received BHAs. One hundred fifty-nine patients (89%) were on a BHA before and/or during Ra-223. Sixty-seven patients received denosumab (38%), 63 received zoledronic acid (36%), and 29 received both nonconcurrently (16%). Eleven patients (6.2%) experienced a fracture after starting Ra-223, 9 of which occurred while on prior and/or concurrent BHA. We observed a 5.7% fracture rate for mCRPC patients who received combination therapy and denosumab or zoledronic acid.

      Conclusion

      This real-world analysis demonstrating a low fracture rate in patients with mCRPC receiving a BHA while on Ra-223 and abiraterone or enzalutamide may inform current clinical practice.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Genitourinary Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • 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.
        Lancet Oncol. 2019; 20: 408-419https://doi.org/10.1016/S1470-2045(18)30860-X
        • Bray F
        • Ferlay J
        • Soerjomataram I
        • Siegel RL
        • Torre LA
        • Jemal A
        Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
        CA Cancer J Clin. 2018; (Published online)https://doi.org/10.3322/caac.21492
      1. Prostate Cancer — Cancer Stat Facts. Accessed November 30, 2020. Available at: https://seer.cancer.gov/statfacts/html/prost.html

        • Saylor PJ
        • Smith MR
        Bone health and prostate cancer.
        Prostate Cancer Prostatic Dis. 2010; 13: 20-27https://doi.org/10.1038/pcan.2009.50
        • Miller K
        • Steger GG
        • Niepel D
        • Lüftner D.
        Harnessing the potential of therapeutic agents to safeguard bone health in prostate cancer.
        Prostate Cancer Prostatic Dis. 2018; 21: 461-472https://doi.org/10.1038/s41391-018-0060-y
        • Saad F
        • Gleason DM
        • Murray R
        • et al.
        A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma.
        J Natl Cancer Inst. 2002; 94: 1458-1468https://doi.org/10.1093/jnci/94.19.1458
        • Smith MR
        • Coleman RE
        • Klotz L
        • et al.
        Denosumab for the prevention of skeletal complications in metastatic castration-resistant prostate cancer: comparison of skeletal-related events and symptomatic skeletal events.
        Ann Oncol. 2015; 26: 368-374https://doi.org/10.1093/annonc/mdu519
        • Tannock IF
        • de Wit R
        • Berry WR
        • et al.
        Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer.
        N Engl J Med. 2004; (Published online)https://doi.org/10.1056/nejmoa040720
        • De Bono JS
        • Oudard S
        • Ozguroglu M
        • et al.
        Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial.
        Lancet. 2010; (Published online)https://doi.org/10.1016/S0140-6736(10)61389-X
        • de Bono JS
        • Logothetis CJ
        • Molina A
        • et al.
        Abiraterone and increased survival in metastatic prostate cancer.
        N Engl J Med. 2011; (Published online)https://doi.org/10.1056/nejmoa1014618
        • Scher HI
        • Fizazi K
        • Saad F
        • et al.
        Increased survival with enzalutamide in prostate cancer after chemotherapy.
        N Engl J Med. 2012; (Published onlinedoi:10.1056/nejmoa1207506 12)
        • Kantoff PW
        • Higano CS
        • Shore ND
        • et al.
        Sipuleucel-T immunotherapy for castration-resistant prostate cancer.
        N Engl J Med. 2010; (Published onlinedoi:10.1056/nejmoa1001294)
        • Parker C
        • Nilsson S
        • Heinrich D
        • et al.
        Alpha emitter radium-223 and survival in metastatic prostate cancer.
        N Engl J Med. 2013; (Published online)https://doi.org/10.1056/nejmoa1213755
        • Sartor O
        • Vogelzang NJ
        • Sweeney C
        • et al.
        Radium-223 safety, efficacy, and concurrent use with abiraterone or enzalutamide: first U.S. experience from an expanded access program.
        Oncologist. 2018; (Published online)https://doi.org/10.1634/theoncologist.2017-0413
        • Saad F
        • Carles J
        • Gillessen S
        • et al.
        Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial.
        Lancet Oncol. 2016; 17: 1306-1316https://doi.org/10.1016/S1470-2045(16)30173-5
        • Tombal BF
        • Loriot Y
        • Saad F
        • et al.
        Decreased fracture rate by mandating bone-protecting agents in the EORTC 1333/PEACE III trial comparing enzalutamide and Ra223 versus enzalutamide alone: an interim safety analysis.
        J Clin Oncol. 2019; 37 (5007): 5007https://doi.org/10.1200/jco.2019.37.15_suppl.5007
        • Gillessen S
        • Choudhury A
        • Rodriguez-Vita A
        • et al.
        Decreased fracture rate by mandating bone-protecting agents in the EORTC 1333/PEACE III trial combining Ra223 with enzalutamide versus enzalutamide alone: an updated safety analysis.
        Journal of Clinical Oncology. 2021; (5002): 5002https://doi.org/10.1200/jco.2021.39.15_suppl.5002
        • Aragon-Ching JB
        • Ning YM
        • Chen CC
        • et al.
        Higher incidence of Osteonecrosis of the Jaw (ONJ) in patients with metastatic castration resistant prostate cancer treated with anti-angiogenic agents.
        Cancer Invest. 2009; 27: 221-226
        • Bamias A
        • Kastritis E
        • Bamia C
        • et al.
        Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors.
        J Clin Oncol. 2005; 23: 8580-8587https://doi.org/10.1200/JCO.2005.02.8670
        • Ortega C
        • Faggiuolo R
        • Vormola R
        • et al.
        Jaw complications in breast and prostate cancer patients treated with zoledronic acid.
        Acta Oncol. 2006; 45: 216-217https://doi.org/10.1080/02841860500341173
        • Woo SB
        • Hande K
        • Richardson PG
        Osteonecrosis of the jaw and bisphosphonates.
        N Engl J Med. 2005; 353: 99-102