Safety of concomitant therapy with radium‐223 and abiraterone or enzalutamide in a real‐world population

Abstract

Background Real‐world utilization and outcomes of combination therapy for men with metastatic castrate‐resistant prostate cancer (mCRPC) are largely unknown. We evaluated the overall survival (OS) and skeletal‐related events (SREs) among men who received radium‐223 with or without concomitant abiraterone or enzalutamide in the Veterans Affairs (VA) Health System. Methods We reviewed charts of all mCRPC patients who received radium‐223 in the VA from January 2013 to September 2017. We used Cox models to test the association between concomitant therapy versus radium‐223 alone on OS and SRE. Sensitivity analyses were performed for concomitant use of denosumab/bisphosphonates. Results Three hundred and eighteen patients treated with radium‐223 were identified; 116/318 (37%) received concomitant abiraterone/enzalutamide. Two hundred and seventy‐seven (87%) patients died during follow‐up. Patients who received concomitant therapy were younger at radium‐223 initiation (median age 68 vs. 70, p = .027) and had a longer follow‐up (median 29.5 vs. 17.9 months, p = .030). There was no OS benefit for those on concomitant therapy (hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.67–1.12, p = .28). There was a trend for an increased SRE risk for patients on concomitant therapy (HR: 1.87, 95% CI: 0.96–3.61, p = .066), but this was not significant. When analyses were limited to men using bone heath agents, similar results were seen for OS (HR: 0.86, 95% CI 0.64–1.15, p = .30) and SRE (HR: 2.36, 95% CI: 0.94–5.94, p = .068). Conclusions Despite the common use of concomitant therapy in this real‐world study, there was no difference in OS among mCRPC patients. A nonsignificant increased SRE risk was observed. Further work needs to evaluate the optimal sequence, timing, and safety of combination therapies.

Real-world effectiveness, long-term safety and treatment pathway integration of radium-223 therapy in patients with metastatic castration-resistant prostate cancer

“…When 223 Ra monotherapy was compared with standard-of-care, the estimated 36-month fracture risk in the respective groups was 19% vs. 10% (HR 1.61; 95% CI: 0.96–3.02) ( 43 ). Regimens combining use of 223 Ra and abiraterone (plus prednisolone) or enzalutamide have been reported in real-world studies ( 44 – 48 ). However, based on a significantly increased risk of fractures when 223 Ra was used in combination with abiraterone plus prednisolone in the ERA 223 phase 3 RCT ( 49 ), this combination is now contraindicated in the EU ( 2 ) and is not recommended in the US ( 3 ).…”

The safety of radium-223 combined with new-generation hormonal agents in bone metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis

“…There was no significant difference in the incidence of SSEs among all groups ( Figure 2 , and Supplementary Table 1 and 2 ). 5 , 6 , 10 , 21 , 27 , 28 The pairwise comparison of SSEs and SSE-FS between the 223 Ra+NHA combination group and the 223 Ra monotherapy group did not yield significant differences (SMD: 0.11, 95% CI: −0.13–1.01, I 2 = 80%, P = 0.13; and ). 6 , 27 , 28 This result suggested that the use of 223 Ra combined with NHAs did not cause a higher incidence of SSEs or shorter SSE-FS.…”

Radium-223 Utilization Patterns and Outcomes in Clinical Practice

“…Indeed, we previously showed that many men within this cohort were treated with concomitant radium and ARTA, though this did not impact OS. 20 Notably, some patients may have been diagnosed with mCRPC prior to the FDA approval of radium-223 and as such may potentially have received treatment later in the disease course than desired. We did not capture potential off-label use of radium-223 for patients with nonbony metastases due to our inclusion criteria.…”