Co-treatment with Radium-223 and Enzalutamide: Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC) from a Prospective Multicenter Observational Study

Objectives: REASSURE is a prospective, non-interventional, multicenter study of patients with metastatic castration-resistant prostate cancer (mCRPC); designed to assess the short- and long-term safety (7-year follow-up) of patients treated with radium-223 in real-world clinical practice. Patients received all treatments based on investigator decision. The objective of this exploratory analysis was to evaluate the real-world clinical outcomes of the combined use (concurrent or layered) of radium-223 and enzalutamide.

Methods: All patients received radium-223. Three patient groups were defined based on the timing of initiation of enzalutamide and radium-223: concurrent group (patients initiated the two drugs within 30 days of each other), layered group (patients initiated one of the two drugs ≥30 days after first treatment with the other), and naïve group (patients who were enzalutamide naïve during the observation period). Patients treated sequentially are not discussed. Descriptive statistics were generated for patient characteristics at the start of radium-223 therapy. Symptomatic skeletal event (SSE) rate, fracture rate, bone health agent (BHA) use, overall survival (OS), and cause of death were assessed. SSEs were musculoskeletal adverse events (fractures, surgery to bone, or spinal cord compression), radiotherapy to bone to relieve skeletal symptoms, or SSEs documented as a type of progression.

Results: As of November 2017, 1439 patients had received radium-223 with a median follow-up time of 9.1 months. Most of the patients treated with radium-223 were enzalutamide-naïve (n=763, 53%); layered treatment with radium-223 and enzalutamide was more frequent (n=220, 15%) than concurrent treatment (n=47, 3%). Sequential treatment was observed in 404 (28%) of the patients. SSEs were reported in 245 patients (17%) overall, in 4 (9%) patients treated concurrently with radium-223 and enzalutamide, in 35 (16%) patients treated in a layered fashion, and in 127 (17%) enzalutamide-naïve patients. Pathological bone fractures were reported in 24 (2%) patients overall, with no fractures reported in the concurrent radium-223 and enzalutamide group, 1 fracture (<1%) in the layered group, and 17 fractures (2%) in the enzalutamide-naïve group. Only 708 patients (49%) had documented BHA use at baseline. Approximately half of patients treated with radium-223 and enzalutamide also received concomitant BHAs (concurrent group, 55%; layered group, 48%). A majority of patients in all treatment groups (≥66%) received 5 or 6 injections of radium-223. Median OS was 19.7 months in the concurrent group, 15.0 months in the layered group, and 15.8 months in the enzalutamide-naïve group. [Table]

Conclusions: In this non-interventional study, concurrent or layered treatment with radium-223 and enzalutamide did not appear to increase the rate of SSEs or fractures. Patients in the concurrent treatment group seemed to have less-advanced disease than those in the layered or naïve groups, as indicated by a lower percentage of patients with prior chemotherapy. This may have contributed to the observed longer median OS and lower rates of SSEs in the concurrent group. An ongoing Phase III trial (PEACE III; NCT02194842) is investigating the combination of radium-223 and enzalutamide as first-line therapy in asymptomatic patients with mCRPC.

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