Fracture risk after radium-223 (Ra-223) in metastatic castration resistant prostate cancer (mCRPC).

Abstract

e16513 Background: Ra-223 improves overall survival in patients with mCRPC, but is associated with increased risk of fracture when used in combination with abiraterone and prednisolone. We have assessed time to first new fracture in men with mCRPC receiving Ra-223 monotherapy, imaged using whole body MRI. Methods: In a prospective phase II study, patients with chemotherapy-naïve, bone mCRPC were randomised (1:1) to receive Ra-223 at 55 or 88 kBq/kg for 6 cycles, at 4-week intervals (REASURE; ISRCTN17805587). Whole body MRI was done at baseline, at cycles 2 and 4, and 1 month post-treatment. Subsequent imaging was done as clinically indicated. All scans were centrally reviewed to describe the time to first new fracture and characteristics of fractures. Time to new fracture was analysed using Kaplan Meier methods; comparisons of time to fracture between groups were based on log-rank tests. Results: 36 evaluable patients received a median of 6 cycles of Ra-223; scans were available for 35 patients. For these 35 patients, median age was 75 years (IQR: 73-80). 3 (9%) were receiving bone health agents at trial entry; 8 (23%) had received prior abiraterone or enzalutamide. 21 (60%) patients developed new fractures between randomisation and 2 years after completing treatment with radium-223. The spine was the most common location for fractures (14 patients). Median time to new fracture from randomisation was 10.8 months (95% CI: 6.2-18.2). Freedom from new fracture at 2 years post-randomisation was 21% (95% CI: 7 – 39%). Time to first new fracture was not associated with Ra-223 dose (55 kBq/kg: 10/18 patients experienced a fracture vs 88kBq/kg: 11/17; p = 0.93) or baseline use of bone health agents (3/3 vs 18/32; p = 0.09). Patients with Extent of Disease (EOD) ≥2 (defined as ≥6 metastatic sites/superscan) had earlier time to first new fracture compared to patients with EOD 1 (defined as < 6 metastatic sites) (11/18 vs 10/17; hazard ratio = 2.7, 95% confidence interval = 1.0 – 6.8; p = 0.04). Conclusions: New fractures are commonly seen on imaging in men with mCRPC during and after treatment with Ra-223 monotherapy. This observation supports treatment guidelines that recommend the use of bone health agents in men with mCRPC. Clinical trial information: ISRCTN17805587.