Radium-223 retreatment in an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases: 2-year follow-up.

Abstract

178 Background: Radium-223 (Ra-223) treatment (tx) is indicated for patients (pts) with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases (mets) (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 pts 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. Methods: Pts with CRPC and bone mets who completed 6 initial Ra-223 inj with no disease progression in bone and later progressed were eligible for Ra-223 re-tx (6 additional Ra-223 inj), provided that hematologic parameters were adequate. No concomitant cytotoxic agents were allowed; other concomitant agents (eg, abiraterone, enzalutamide) were allowed at investigator discretion. The primary objective was safety. Exploratory objectives were time to radiographic bone progression, radiographic progression-free survival (rPFS), overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE-free survival, all calculated from re-tx start. Pts will be followed for safety up to 7 years after last Ra-223 dose; an active 2-year follow-up evaluated exploratory objectives. Safety results from the active follow-up period and updated efficacy are reported. Results: 44 pts were re-treated with Ra-223; 29 (66%) completed all 6 inj (median number inj = 6). 34 (77%) of 44 pts entered active follow-up, during which no new safety concerns were noted. One new primary malignancy was reported (basal cell carcinoma). There were no serious drug-related adverse events. 19 (43%) of 44 pts had an rPFS event (radiographic progression or death); median rPFS was 9.9 months. Only 5 (11%) of 44 pts had radiographic bone progression; median time to radiographic bone progression was not reached. Median OS was 24.4 months. Median time to first SSE and SSE-free survival were 16.7 and 12.8 months, respectively. Conclusions: Re-treating with Ra-223 was well tolerated in this select pt population, led to minimal hematologic toxicity, and provided continued disease control in bone at 2-year follow-up. Clinical trial information: NCT01934790.