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.

A novel prediction model for the completion of six cycles of radium-223 treatment and survival in patients with metastatic castration-resistant prostate cancer

“…Based on these findings, Ra-223 was established as a standard treatment modality for mCRPC patients with predominant bone disease and no visceral metastases [4][5][6]. The approved regimen of Ra-223 is an intravenous injection of 55 kBq/kg of Ra-223, every 4 weeks (q4w), for six cycles [1,4].…”

“…The biological effectiveness of a radionuclide therapy is dose-dependent [7]. Saad et al conducted a phase IIIb, single-arm study in the setting of an international early access program (iEAP) [8] that evaluated the correlation between the number of treatment cycles of Ra-223 (1-4 vs. [5][6] and the OS using a post hoc analysis [7]. The primary endpoints of this study were the safety and survival of patients treated with Ra-223 for symptomatic or asymptomatic mCRPC.…”

Prognosis and safety of radium‐223 with concurrent abiraterone acetate or enzalutamide use for metastatic castration‐resistant prostate cancer: Real‐world data of Japanese patients

“…ARTA could treat metastatic sites other than bone, thus, a combination therapy would be ideal. Indeed, there have been reports of many patients who received Ra‐223 combined with ARTA in a real‐world setting 15,21 . Sartor et al reported that the OS of patients who received Ra‐223 with ARTA, including ABI or ENZ, (40/184, 21.7%) was favorable compared with that of patients who received only Ra‐223 (144/184, 78.3%) in a phase II, U.S. expanded access program 15 .…”

“…Sartor et al reported that the OS of patients who received Ra‐223 with ARTA, including ABI or ENZ, (40/184, 21.7%) was favorable compared with that of patients who received only Ra‐223 (144/184, 78.3%) in a phase II, U.S. expanded access program 15 . Shore et al also conducted a database retrospective analysis of the efficacy and safety of Ra‐223 combined with ARTA in 625 patients with Mcrpc 21 . Of the 625 patients, 83 (13.3%) received Ra‐223 with ARTA (39 received ABI and 44 received ENZ) and the remaining 542 (86.7%) patients received Ra‐223 alone.…”

Clinical outcomes, management, and treatment patterns in patients with metastatic castration‐resistant prostate cancer treated with radium‐223 in community compared to academic settings

“…4,15 The majority of radium-223 studies were conducted at tertiary or academic sites, and the currently published real-world analyses do not differentiate treatment by site of care, which leaves a paucity of data characterizing any potential treatment differences for mCRPC patients receiving this therapy in academic center (AC) and community practice (CP) settings. 13,[16][17][18][19][20][21][22][23][24] Because of the morbidity and survival benefits offered by radium-223, it is important to understand its current use in both AC and CP settings to ensure access regardless of site of care. In this retrospective analysis, we aimed to address this data gap by assessing the use and survival outcomes of radium-223 in patients treated in AC versus CP sites.…”