Real-world safety and effectiveness of radium-223 (223Ra) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated in the US: The non-interventional REASSURE study.

5050 Background: 223 Ra improved overall survival (OS) and quality of life and demonstrated a favorable safety profile in pts with mCRPC in the phase 3 ALSYMPCA trial. REASSURE (NCT02141438) is a global, prospective, single-arm, observational study of 223 Ra use in pts with mCRPC and bone metastases in routine clinical practice. Here, we present clinical outcomes from the second planned interim analysis of REASSURE for pts treated in the US. Methods: This analysis included pts with confirmed mCRPC with bone metastases scheduled to receive 223 Ra in the US. All pts received ≥1 dose of 223 Ra. Primary endpoints are short- and long-term safety, including incidence of bone marrow suppression and second primary malignancies (SPM). Secondary endpoints included OS and pt-reported pain (Brief Pain Inventory – Short Form [BPI–SF] scores). A clinically meaningful pain response was defined as a decrease from baseline of ≥2 points in BPI-SF worst pain item. Results: Pts were enrolled from 2014–2017. Overall, 498 pts were included in this analysis. At the data cut-off (20 March 2019), the median duration of observation was 11.9 months (0.4–41.3). Most pts (81%) had bone metastases only; 69% of pts received 5–6 223 Ra injections. Overall, 77% of pts had received ≥1 prior life-prolonging therapies: abiraterone (45%), enzalutamide (48%), docetaxel (25%), cabazitaxel (6%), or sipuleucel-T (24%). Concomitant enzalutamide was received by 31% of pts, and 47% received concomitant bone health agents. After 223 Ra, 31% of pts received ≥1 life prolonging therapies. During treatment, 208/358 (58%) pts with a baseline BPI-SF ≥2 had a clinically meaningful pain response. Any-grade and grade ≥3 drug-related treatment-emergent adverse events (TEAEs) occurred in 32% and 10% of pts, respectively. Drug-related TEAEs resulted in 223 Ra discontinuation in 4% of pts. Treatment-emergent and drug-related serious AEs (SAEs) occurred in 21% and 6% of pts, respectively. The most common (>5% of pts) any-grade drug-related TEAEs were diarrhea (10%), fatigue (9%), anemia (8%) and nausea (7%). Overall, 4% of pts had fractures; 2% of pts developed bone disorders. Eleven SPMs occurred in 10 pts (2%). In total, 60% of pts died during study follow-up. Median OS was 17.8 months (95% CI 15.6–19.4). Conclusions: Within the current treatment landscape in routine clinical practice in the US, median OS after 223 Ra treatment was close to 18 months. A majority of pts completed 5–6 223 Ra injections. The known safety profile of 223 Ra was confirmed with no new safety signals. Over half of pts with pain at baseline had a clinically meaningful pain response during 223 Ra treatment. Clinical trial information: NCT02141438 .