210 Background: Ra-223 is an α-emitter that binds to the newly formed bone matrix and targets osteoblastic metastatic lesions. Treatment with Ra-223 delays symptomatic skeletal-related events (SREs) and improves overall survival (OS) in men with mCRPC. Concerns about the efficacy and safety of Ra-223 in the pre-chemotherapy space, given alone or in combination with Abiraterone Acetate (AA) or enzalutamide (ENZ), have been raised. Methods: To determine the feasibility, efficacy and safety profile of Ra-223 given alone or in combination with AA or ENZ to men with docetaxel-naïve mCRPC a retrospective study was conducted. PSA decline, rPFS and safety data for patients (pts) treated at Cleveland Clinic (CC) and Tulane University (TU) were analyzed. Results: Fifty-one (27 CC and 24 TU) chemo-naïve mCRPC pts with bone metastases were identified. The median age was 63 (46-87). Testosterone suppression was maintained during treatment. Pre-treatment alkaline phosphatase (ALP) was elevated in 16 pts (33%). In addition to bone, 24 pts (47%) had soft-tissue metastases. While 23 pts received Ra-223 alone, 22 pts (43%) received concomitant AA or ENZ therapy. To date, the median number of Ra-223 cycles received is 5 (1-6) with 39% of pts (20/51) receiving all 6 cycles. PSA declines >30% were observed in 31% of pts. All but one pt had at least some decline in ALP. ALP decline >30% was observed in 68% of pts. Reasons for treatment discontinuation included; completion of 6 cycles 39% (20/51); PD 35% (18/51); AEs 8% (4/51) and pt choice 4% (2/51). Grade (G) 3/4 AEs were observed in 4 pts; G3 anemia (n=3) and G4 thrombocytopenia (n=1). The vast majority of pts had PSA progression (81%) and 42% of pts have died. Estimated median time to PSA progression and OS are 3.9 (95% C.I. 1.84-4.82) and 11.0 months (95% C.I. 7.5-16.4), respectively. Pts with normal baseline hemoglobin levels and those who received concomitant AA tended to have better PSA progression-free and OS (p<.06). Conclusions: Treatment with Ra-223 in combination with AA or ENZ in chemo-naïve mCRPC pts is feasible with no new safety signals of concern. Further evaluation of the combination of AA or ENZ with Ra-223 in this setting is warranted.