Abstract 672P
Background
Ra 223 is a bone-targeted radionuclide that improves overall survival and time to skeletal-related events. Ra 223 increases the risk of fracture when used in combination with abiraterone. We have done a prospective phase 2 study of Ra 223 monotherapy, with an exploratory analysis of risk of fracture.
Methods
Patients with chemotherapy-naïve, bone-only, progressive mCRPC were randomised to one of two Ra 223 dose-levels; 55 or 88 kBq/Kg, q4 weeks for 6 cycles. Whole body MRI was done at baseline, at cycle 2 and 4, and 1 month post treatment. All imaging studies after trial enrolment were reviewed. Time to fracture was analysed using Kaplan Meier curves and association with other variables assessed via log-rank tests and Cox-Proportional Hazards.
Results
36 patients were evaluable, of whom 4 had a bone health agent. Overall, 74 new fractures were identified in 20 patients, which were symptomatic in 10 patients. Most fractures (50/74) occurred at sites of uninvolved bone. Freedom from fracture was 56% (95% CI: 35.3-71.6) at 12 months. On univariate analysis, extent of bone metastases and baseline alkaline phosphatase were associated with risk of fracture. On multivariate analysis, prior corticosteroid use was the only variable associated with fracture risk.
Conclusions
Fractures are commonly seen on MRI during and after Ra 223 treatment. While not all fractures are symptomatic, these findings underscore the importance of using bone-health agents in all mCRPC patients, including the ones treated with Ra 223.
Clinical trial identification
ISRCTN17805587.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Bayer.
Disclosure
C. Parker: Honoraria (self), Research grant/Funding (self): Bayer; Honoraria (self): Janssen. All other authors have declared no conflicts of interest.