85 Background: Radium-223 (Ra-223) is approved for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with symptomatic bone metastases based on its demonstrated overall survival (OS) benefit and favorable safety profile. REASSURE (NCT02141438) was a 10-year, global, prospective, single-arm, observational study of Ra-223 use in pts with bone predominant mCRPC within routine clinical settings. Here we report patient characteristics and outcomes for the US pts who received Ra-223 in the REASSURE global study. Methods: Pts were recruited from August 2014 through December 2017. The observation period for each patient was the start of therapy with Ra-223 to death, withdrawal of consent, lost to follow-up, or end of this study (maximum of 7 years after last administration). In this descriptive final analysis (data cutoff 10-24-2024), we evaluated baseline characteristics, primary endpoints: hematological toxicities, second primary malignancies (SPMs), and secondary endpoints: OS, bone fractures, and pain response (to be reported in full presentation). Results: A total of 498 pts (median age 74 years, 83% White, 12% Black or African American, 2% Asian) with mCRPC comprise the US subset. The proportion of pts with an Eastern Cooperative Oncology Group score of 0 or 1 at study entry was 79%. Prior treatments included systemic anti-cancer therapy in 491 pts (99%), radiotherapy in 312 pts (63%), and blood transfusions in 38 pts (8%). A total of 312 pts (63%) completed 6 injections of Ra-223. The median duration of observation from the start of Ra-223 treatment was 19.0 months (range, 0.4-95.3 months). Any-grade drug-related hematological treatment-emergent adverse events (TEAEs) occurred in 50 pts (10%) (Table). Grade ≥3 drug-related hematological TEAEs occurred in 31 pts (6%). Ten SPMs were reported for 10 pts (2%). The most common sites of SPMs were lung, skin, and pancreas (2 pts each). Median OS was 17.4 months (95% CI, 15.3-19.3 months). A total of 271 pts (54%) received a prior bone protective agent (BPA). Bone fractures were reported in 35 pts (7%) overall, including in 15 pts who had received a prior BPA (6%) and in 20 pts who had not received a prior BPA (9%). Conclusions: In this descriptive analysis of 10-year real-world data from the US, Ra-223 demonstrated a favorable long-term hematological safety profile in pts with mCRPC. Importantly, incidence of SPMs was low across the observation period and relative to national mCRPC data. OS was consistent with other contemporary studies. Despite underutilization of BPAs, the incidence of bone fractures remained low with Ra-223, a bone directed therapy. n=498 Any grade drug-related hematological TEAEs, n (%) Anemia 40 (8.0) Leukopenia 6 (1.2) Myelosuppression 1 (0.2) Neutropenia 6 (1.2) Pancytopenia 3 (0.6) Thrombocytopenia 7 (1.4) Bone fractures, n (%) 35 (7.0) Number of SPMs, n (%) 10 in 10 pts (2.0)
Higano et al. (Sun,) studied this question.