2-Year Follow-up of Radium-223 Re-treatment in an International, Open-Label, Phase 1/2 Study in Patients With Castration-Resistant Prostate Cancer and Bone Metastases
Radium-223 (Ra-223) treatment (tx) is indicated for patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases (6 × 55 kBq/kg IV injections [inj]; 1 inj q4wk). Early results of an international, open-label, phase 1/2 study (NCT01934790) showed that re-treating patients with Ra-223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from a 2-year follow-up.
Patients with CRPC and bone metastases who completed 6 initial Ra-223 inj with no disease progression in bone and later progressed were eligible for Ra-223 re-tx (up to 6 additional Ra-223 inj), provided that hematologic parameters were adequate. No concomitant cytotoxic agents were allowed; other concomitant agents (eg, abiraterone and enzalutamide) were allowed at investigator discretion. The primary objective was safety. Exploratory objectives included time to radiographic bone progression, radiographic progression-free survival (rPFS), time to total alkaline phosphatase (tALP) and prostate-specific antigen (PSA) progression, overall survival (OS), and time to first symptomatic skeletal event (SSE), all calculated from start of re-tx. The evaluation of safety and exploratory objectives included an active 2-year follow-up. Safety results from the active follow-up period and updated efficacy are reported.
44 patients were re-treated with Ra-223; 29 (66%) completed all 6 inj (median number inj = 6). 34 (77%) of 44 patients entered active follow-up, during which no new safety concerns were noted. One new primary malignancy was reported (basal cell carcinoma; not considered related to study drug). There were no serious drug-related adverse events. 19 (43%) of 44 patients had an rPFS event (radiographic progression or death); median rPFS was 9.9 months. Only 5 (11%) of 44 patients had radiographic bone progression; median time to radiographic bone progression was not reached. Median time to tALP progression was not reached, median time to PSA progression was 2.2 months. Median OS was 24.4 months. Median time to first SSE was 16.7 months.
Re-treating patients with Ra-223 was well tolerated in this select population, led to minimal hematologic toxicity, and provided continued disease control in bone at the 2-year follow-up.
Funding: Bayer HealthCare Pharmaceuticals