Background: Ra-223 is an approved α-emitter that prolongs survival in CRPC with symptomatic bone mets. We presented data from a phase 1/2a study of safety and antitumor effects of Ra-223 + D vs D alone showing that Ra-223 + D is safe and well tolerated (ESMO 2014). Here we report the effect of Ra-223 + D vs D on bALP and PSA dynamics. Methods: D-eligible pts with progressing CRPC and ≥ 2 bone mets received (2:1) Ra-223 (50 kBq/kg q 6 wk × 5) + D (60 mg/m² q 3 wk × 10) or D (75 mg/m² q 3 wk with a step-down option to 60 mg/m²). bALP and PSA were recorded q 3 wk during the first 6-wk cycle, then q 6 wk and q 3 wk, respectively, and analyzed at a central laboratory. Changes in both markers are described by the % of pts whose best responses were ≥ 30%, > 50%, and > 80% declines from baseline (3 wk post last D injection); pts with elevated baseline bALP ( ≥ 21 µg/L) were included for bALP analysis. bALP to below upper limit of normal (ULN) was also recorded, regardless of % decline. Results: 46 pts (33 Ra-223 + D vs 13 D alone) were enrolled. As of January 2015, 24 (Ra-223 + D) vs 5 (D) pts had all planned injections. Median (range) baseline PSA was 99 µg/L (3-1000) for Ra-223 + D pts and 43 µg/L (4-1042) for D pts. The table shows maximal changes in PSA and bALP levels from baseline. No pt had a bALP increase. Pts continue in follow-up (to 12 mo after first injection) for safety and progression. Conclusions: Ra-223 + D appears to favorably impact post-treatment declines in PSA and bALP and to be particularly effective at normalizing bALP levels vs D alone. Clinical benefits of such changes in serum markers require validation in larger prospective studies. Clinical trial information: NCT01106352

*Pts with baseline bALP > ULN (> 21 μg/L). N/A = not applicable.