Hematologic Safety of Radium-223 Dichloride: Baseline Prognostic Factors Associated With Myelosuppression in the ALSYMPCA Trial.

BACKGROUND: Myelosuppression is common in patients with progressive castration-resistant prostate cancer and bone metastases. Radium-223 prolongs overall survival in these patients but may cause myelosuppression; understanding risk factors will improve clinical decision making. We describe hematologic safety of radium-223 in ALSYMPCA and post hoc analyses identifying patients at increased risk for hematologic toxicity. PATIENTS AND METHODS: Hematologic parameters and adverse events were analyzed. Multivariate analyses assessing baseline risk factors for hematologic toxicities were performed separately for radium-223 and placebo patients. RESULTS: Nine hundred one patients received radium-223 (n = 600) or placebo (n = 301); 65% of radium-223 and 48% of placebo patients had the full 6 cycles. Grade 3/4 thrombocytopenia was more common in radium-223 versus placebo patients (6% vs. 2%). Logistic regression analyses identified significant baseline predictors for grade 2-4 hematologic toxicities related to radium-223 treatment: extent of disease (6-20 vs. < 6 bone metastases; odds ratio [OR] = 2.76; P = .022) and elevated prostate-specific antigen (OR = 1.65; P = .006) for anemia; prior docetaxel (OR = 2.16; P = .035), decreased hemoglobin (OR = 1.35; P = .008), and decreased platelets (OR = 1.44; P = .030) for thrombocytopenia. Neutropenia events were too few in placebo patients for a comparative analysis. There were no significant associations between hematologic toxicities and number of radium-223 injections received (4-6 vs. 1-3). CONCLUSION: Radium-223 has a favorable safety profile with a low myelosuppression incidence. Understanding baseline factors associated with myelosuppression may assist clinicians in avoiding severe myelosuppression events with radium-223.