Changes in alkaline phosphatase (ALP) dynamics and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223 in an international early access program (EAP)

Abstract

Background: Identifying a reliable marker of efficacy for radium-223 dichloride (Ra- 223) would aid in the clinical management of mCRPC patients (pts). In exploratory analyses of mCRPC pts with symptomatic bone metastases treated with Ra-223 in the ALSYMPCA trial, OS was significantly longer in pts with a confirmed decline in ALP levels from baseline at week 12, compared with pts without a confirmed ALP decline. Here, we present data on ALP dynamics and OS and time to first symptomatic skeletal event (SSE) in pts treated with Ra-223 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, every 4 weeks for up to 6 cycles. Co-primary endpoints were safety and OS. Exploratory analyses investigated whether a confirmed decline (any magnitude) in ALP levels was associated with OS and time to first SSE. Results: 696 pts received at least one Ra-223 cycle. Of those, 398 (57%) pts had a confirmed decline in ALP and 298 (43%) had no confirmed ALP decline. Key baseline characteristics are shown (Table). More pts with a confirmed ALP decline (374, 94%) received 5-6 Ra- 223 injections than those with no ALP decline (99, 33%). Hazard ratios (HR) for confirmed ALP decline at week 12 vs no decline suggest a strong association of ALP decline with both longer OS (HR 0.299, 95% CI 0.227-0.395) and longer time to first SSE (HR 0.474, 95% CI 0.340-0.662) (Table). Conclusions: In this EAP, which is relevant for pts currently treated in clinical practice, decline in ALP was associated with longer OS and time to first SSE.