Background: In the updated analysis of the ALSYMPCA study, Ra-223 significantly improved median survival by 3.6 mo vs placebo (Pbo) in 921 CRPC patients (pts) with bone mets (HR = 0.695; 95% CI, 0.581-0.832; p = 0.00007) and had a highly favorable safety profile (Parker et al. ASCO 2012). The hematologic safety profile and results from a post hoc analysis assessing prognostic factors for changes in hematologic parameters in ALSYMPCA pts are presented. Methods: Pts were randomized 2:1 to 6 injections (inj) of Ra-223 (50 kBq/kg IV) q4wk or matching Pbo and stratified by prior docetaxel (D) use, total alkaline phosphatase (tALP), and current bisphosphonate use.Multivariate regression analysis was performed to explore the relationship of 6 baseline factors (Table) with maximum % change of hematologic parameters from baseline up to 24 wk on treatment (tx). Results: The updated analysis included 901 pts (safety population; Ra-223, n = 600; Pbo, n = 301). Overall grade 3/4 AEs were similar between Ra-223 and Pbo groups, with neutropenia in 2% and 1%, thrombocytopenia in 6% and 2%, and anemia in 13% and 13% of Ra-223 and Pbo groups, respectively. Tx with Ra-223, prior D use, extent of disease (EOD) > 6 bone mets, and tALP ≥ 220 U/L, but not current bisphosphonate use, were associated with decreases from baseline in hemoglobin (Hb), neutrophils, or platelets; prior EBRT to bone for pain was associated with an increase. The significance of the relationship between baseline factors and changes in hematologic parameters is summarized in the Table. Conclusions: Overall, there was a low risk for hematologic AEs with Ra-223 tx in CRPC pts with bone mets. The strongest prognostic factors for decreases in neutrophils and platelets were Ra-223 tx and prior D use. Baseline tALP ≥ 220 U/L was a strong predictor of decrease in Hb. Clinical trial information: NCT00699751.

^*p < 0.05.