Background: Ra-223 is an approved α-emitter prolonging survival in CRPC with symptomatic bone mets. We conducted a phase 1/2a study examining the safety and antitumor effects of Ra-223 + D vs D alone, and previously presented data 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 were randomized 2:1 to Ra-223 (50 kBq/kg q 6 wk × 5) + D (60 mg/m² q 3 wk × 10) vs D (75 mg/m² q 3 wk with step-down option to 60 mg/m²). bALP and PSA were recorded q 3 wk during 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 who achieved ≥ 30%, > 50%, and > 80% declines between baseline and the safety follow-up visit (3 wk post last D injection) as their best response; pts with elevated baseline bALP (≥ 21 µg/L) levels were included for the bALP analysis. bALP to below the 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 October 2014, 21 (Ra-223 + D) vs 5 (D) pts had received all planned study treatment. Median (range) baseline PSA was 99 µg/L (3-1000) for Ra-223 + D pts and 43 µg/L (4-1042) for D pts. Maximal changes in PSA and bALP levels between baseline and safety follow-up are shown in Table. No pt had a bALP increase. Conclusions: Ra-223 + D appears to favorably impact posttreatment PSA and bALP declines. Ra-223 + D appears particularly effective at normalizing bALP levels vs D alone. The clinical benefits of such changes in serum markers will require validation in larger prospective studies. Clinical trial information: NCT01106352

Abbrevitation: N/A; not applicable.