Real-world characteristics of long-term survivors with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223): An analysis of the global REASSURE study.

74 Background: Ra-223 is an alpha-emitting radionuclide approved to treat mCRPC with bone metastases. The REASSURE study (NCT02141438) assessed the long-term safety (~10 years [yrs]) and overall survival (OS) associated with Ra-223 in clinical practice. This was the most comprehensive and longest-term prospective study focused on safety and efficacy of a radiopharmaceutical in this setting. Methods: Patients (pts) with mCRPC with bone metastases were enrolled from 2014–2017 (final data cut-off: October 2024). We compared pts with extended OS to those without, using a 2-yr cutoff. We evaluated disease history, baseline characteristics, treatment patterns (including prior, concomitant and subsequent treatments), fracture rates, incidence of second primary malignancies (SPMs), and OS from diagnosis of castration resistance and Ra-223 initiation. Analyses were descriptive. Results: Of 1472 pts, 393 (27%) survived ≥2 yrs (median OS 38.1 months) and 1079 (73%) survived <2 yrs (median OS 10.7 months). Respective median age was 71 and 74 yrs; median time from castration resistance to study entry was 9 and 13 months. The table shows key differences between groups. Pts surviving ≥2 yrs had less advanced disease at Ra-223 initiation and lower disease volume versus those surviving <2 yrs; baseline alkaline phosphatase (median 94 vs 158 U/L), prostate-specific antigen (median 22 vs 89 ng/mL) and lactate dehydrogenase (median 214 vs 294 U/L) were also lower. Fewer pts with extended OS received androgen receptor pathway inhibitors and/or taxanes prior to Ra-223, and nearly all completed Ra-223 therapy. Pts with extended OS tended to receive subsequent treatments and had longer median OS from castration resistance diagnosis (Table). Approximately half of pts used bone protective agents, and the observed rates of fractures (≥2 yrs: 16%, <2 yrs: 7%) and SPMs (≥2 yrs: 4%, <2 yrs: 1%) were low. Conclusions: Pts with the longest survival received Ra-223 treatment earlier, with a majority completing therapy and many subsequently receiving additional life-prolonging therapy, all contributing to extended OS. This highlights the significance of careful patient selection when evaluating the benefits of Ra-223. Statistical methods to identify factors associated with long-term survival will be discussed. Clinical trial information: NCT02141438 . OS ≥2 years (N=393) OS <2 years (N=1079) ECOG PS: 0-1, % 87 77 Extent of Disease: <6 / >20 lesions, % 28 / 13 15 / 23 Abiraterone: Prior / Concomitant / Subsequent, % 39 / 17 / 25 51 / 14 / 6 Enzalutamide: Prior / Concomitant / Subsequent, % 29 / 20 / 36 43 / 17 / 7 Docetaxel: Prior / Concomitant / Subsequent, % 26 / 1 / 35 44 / 2 / 12 Cabazitaxel: Prior / Concomitant / Subsequent, % 4 / 0 / 22 12 / 1 / 7 Bone Protective Agent: Prior / Concomitant, % 54 / 50 48 / 38 Completed 6 Ra-223 injections, % 92 48 OS from time of castration resistant cancer, median, months 56.2 27.4