Radium-223 with concomitant bone-targeting agents in metastatic castration-resistant prostate cancer (CRPC) patients treated in an international early access program (EAP)

Abstract

Background: The bone-targeting agents (BTAs) denosumab and bisphosphonates (BPs) are widely used in the supportive care of patients (pts) with CRPC and bone metastases. We present data on pts treated with radium-223 dichloride (Ra-223) with or without a concomitant BTA in an international EAP.Methods: This was a prospective single-arm phase IIIb study of CRPC pts with symptomatic or asymptomatic bone metastases (no visceral disease) recruited from 14 countries. Pts received Ra-223 55 kBq/kg (iv injection) every 4 weeks for 6 cycles. Co-primary endpoints were safety and overall survival (OS). Exploratory analyses investigated the effects of concomitant denosumab (no BPs) or BPs (no denosumab) on OS and symptomatic skeletal events (SSE). Results: 696 pts received at least one Ra-223 cycle. Of those, 127 (18%) pts were treated with concomitant denosumab (no BPs) and 435 (63%) without any concomitant BTAs. Key baseline characteristics are reported in pts treated with Ra-223 with or without a concomitant BTA (Table). Median OS (mOS) and median time to first SSE (mSSE) were longer in pts treated with Ra-223 and denosumab versus pts without a concomitant BTA (Table). While key baseline characteristics in pts treated with Ra-223 and denosumab were similar to pts treated with Ra-223 and BPs, adding BPs to Ra-223 did not appear to improve mOS. However, mSSE was prolonged in pts receiving Ra-223 and BPs versus pts who received Ra-223 without a concomitant BTA (Table). Conclusions: In this EAP, pts treated with Ra-223 and a concomitant BTA appeared to have longer time to first SSE than those treated without a concomitant BTA. However, improvement in OS was observed with denosumab but not with BPs. Prospective randomized controlled studies are required to confirm the benefit of this specific treatment combination in metastatic CRPC.Table: B7DenosumabBPsNo denosumab/ no BPsN = 127N = 125N = 435Baseline characteristicsECOG PS, n (%)058 (46%)55 (44%)144 (33%)155 (43%)54 (43%)234 (54%)≥214 (11%)16 (13%)57 (13%)Pain, n (%)123122413Mild75 (61%)72 (59%)218 (53%)Moderate-severe19 (15%)24 (20%)113 (27%)None29 (24%)26 (21%)82 (20%)ALP (U/L), n127125433Median121.0137.0168.0PSA (µg/L), n127124433Median91.2118.5174.6Efficacy outcomeOverall survivalMedian, monthsNR12.713.495% CINA10.9–NA11.7–NAHazard ratio (95% CI)0.630 (0.431– 0.922)0.846 (0.584– 1.226)-Time to first SSEMedian, months17.0NR15.895% CI17.0–17.5NA10.9–19.1Hazard ratio (95% CI)0.761 (0.493– 1.173)0.498 (0.294– 0.845)-NR/A = not reached/available. Open table in a new tab NR/A = not reached/available.