A phase IIa study of radium-223 dichloride (Ra-223) alone or in combination with abiraterone acetate or enzalutamide in metastatic castration-resistant prostate cancer (mCRPC)

Abstract

Background: Ra‐223 demonstrated improvements in overall survival (OS) and time to symptomatic skeletal events (SSEs) in patients (pts) with mCRPC and bone metastases in the ALSYMPCA study (Parker C et al. N Engl J Med 2013; 369:213‐223). The current study investigated antitumor activity of Ra‐223 alone or in combination with abiraterone (abi) or enzalutamide (enza). Methods: In this multicenter, open‐label phase 2a study, pts with mCRPC and boneonly metastases were randomized (1:1:1) to: six injections of Ra‐223 (55 kBq/kg, q4w), Ra‐223+abi (1000 mg qd + prednisone 5 mg bid), or Ra‐223+enza (160 mg qd). The primary endpoint was bone scan lesion area response rate (BSLA RR) at Week 24 based on the quantified technetium‐99 bone scan. BSLA RR, defined as>30% decrease from baseline (BL), was evaluated centrally. The hypothesis of a BSLA RR≥5% at Week 24 was tested in each arm separately. No cross‐arm comparisons were planned. Secondary endpoints are shown in the table. Results: 68 pts were randomized; 63 received treatment. The most common reason for treatment discontinuation was disease progression (50.0%). Approximately 36.5% of pts used bone health agents (BHAs) at BL. The primary endpoint of BSLA RR at Week 24 was 57.9%, 50.0%, and 22.2% for the Ra‐223+abi, Ra‐223+enza, and Ra‐223 groups, respectively. Median SSE‐free survival (SSE‐FS) was not reached, 19.91, and 11.93 months and median OS was 37.55, 29.86, and 35.81 months, for the Ra‐223+abi, Ra‐223+enza, and Ra‐223 groups, respectively. Fracture rates were lower in pts with vs without BL BHAs; 3/23 (13.0%) vs 10/40 (25.0%), respectively. 17, 18, and 8 pts receiving Ra‐223+abi, Ra‐223+enza, and Ra‐223 experienced related treatment‐emergent adverse events, respectively. Conclusions: The primary endpoint of BSLA response was met in each treatment arm. Overall, OS does not appear to correlate with BSLA RR in this small study population. (Table Presented) .