Concurrent or layered treatment with radium-223 and enzalutamide or abiraterone/prednisone: real-world clinical outcomes in patients with metastatic castration-resistant prostate cancer

Abstract

Background: In this study, we evaluated real-world data on radium-223 plus abiraterone/prednisone or enzalutamide. Previously, the ERA 223 trial (NCT02043678) demonstrated increased fracture risk with concurrent treatment with radium-223 and abiraterone plus prednisone/prednisolone in patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods: We used the Flatiron Health database to perform a retrospective study of patients with mCRPC treated with radium-223. Treatment with radium-223 plus abiraterone/prednisone or enzalutamide was defined as concurrent if both drugs started within 30 days of one another, or layered when the second drug started ≥30 days after the first. The index date was defined as the day of the first radium-223 dose. Outcome measures included symptomatic skeletal events (SSEs), overall survival (OS), and patterns of treatments received.

Results: Of the 625 patients treated with radium-223, 22% received it together with abiraterone/prednisone and 27% with enzalutamide. When these agents were combined, they were often initiated in a layered fashion (73% layered, 23% concurrent). Prior or concomitant bone health agents (BHAs) were received by 67% and 55% of patients, respectively. Median follow-up was 9 months. Overall, incidence rates for SSEs and pathologic fractures were 0.35 and 0.11 patients per person-year, respectively. Median OS from mCRPC diagnosis was 28.1 months.

Conclusions: In this real-world setting, combination treatments with radium-223 and abiraterone/prednisone or enzalutamide were common. These agents were more commonly given in a layered than a concurrent fashion. Incidence rates for SSEs were reduced when BHAs were used; however, BHAs were underutilized.

Conflict of interest statement

NS reports fees from Amgen, Astellas, Bayer, Dendreon, Ferring, Genentech/Roche, Janssen, Medivation/Astellas, Myovant, Pfizer, and Tolmar. CSH reports fees from Aptevo, Asana Aragon Pharma, Astellas, AstraZeneca, Bayer, Blue Earth Diagnostics, Churchill Pharma, Clovis, Dendreon, eFFECTOR Therapeutics, Endocyte, Emergent BioSolutions, Ferring, Genentech, Hinova, Hoffman-Laroche, Janssen, Medivation, Myriad, Orion, and Pfizer. DJG reports grants and/or fees from Acerta Pharma, the American Association for Cancer Research, Astellas, AstraZeneca, Axess Oncology, Bayer, BMS, Calithera, Capio Biosciences, EMD Serono, Exelixis, Flatiron, Ipsen, Janssen, Leidos Biomedical Research, Merck Sharp & Dohme, Michael J Hennessey Associates, Millennium Med Publishing, Modra Pharmaceuticals, Myovant Sciences, NCI Nektar Therapeutics, Novartis, Pfizer, Physician Education Resource, Sanofi, UroGPO, UroToday, and Vizuri Health Sciences. CNS reports fees from Astellas, AstraZeneca, Bayer, Exelixis, Janssen, Medivation, Medscape, Pfizer, Roche-Genentech, and Sanofi. FS reports fees from Astellas, AstraZeneca, Bayer, Janssen, Merck, Pfizer, and Sanofi. BT reports grants and fees from Amgen, Astellas, Bayer, Ferring, Janssen, and Sanofi-Genzyme. KM reports fees from Astellas, Bayer, BMS, Ferring, Janssen, MSD, Novartis, Pfizer, and Roche. JK was a Bayer employee until November 2019. XJ is a Bayer employee. KT was a Bayer employee until May 2019. OS reports grand and/or fees from Advanced Accelerator Applications, Astellas, AstraZeneca, Bayer, Bellicum, Blue Earth Diagnostics, Inc., Bristol Myers Squibb, Celgene, Constellation, Dendreon, EMD Serono, Innocrin, Invitae, Johnson & Johnson, Merck, Myovant, Pfizer, Sanofi, and SOTIO.

Figures

Fig. 1. SSE and pathologic fracture incidence rates.

a Overall SSE and pathologic fracture incidence rates. b SSE incidence rates, stratified by concomitant BHA usage. c Pathologic fracture incidence rates, stratified by concomitant BHA usage. Concurrent = both treatments starting within 30 days of each other; layered = one treatment starting ≥30 days after the other. BHA bone health agent, SSE symptomatic skeletal event. *Two patients had no follow-up data and were excluded from the analysis.

Fig. 2. Overall survival.

mCRPC metastatic castration-resistant protate cancer. Concurrent = both treatments starting within 30 days of each other; layered = one treatment starting ≥30 days after the other. *Two patients had no follow-up data and were excluded from the analysis.