Radium-223 Safety and Efficacy Sustained in 7-Year Real-World Update

The established safety and efficacy of the alpha-emitting radionuclide radium-223 (Xofigo) in patients with metastatic castration-resistant prostate cancer (CRPC) and bone metastases were sustained in 7-year follow-up data from the real-world phase 3 REASSURE trial (NCT02141438), according to findings presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

At a median follow-up of 17 months (range, 0.3-95.4), 50% of the 1472 patients evaluated in REASSURE had experienced at least 1 adverse event (AE) of any grade, with 37% of patients experiencing treatment-emergent, drug-related AEs. Diarrhea (11%), anemia (9%), nausea (9%), and fatigue (8%) were the most common treatment-emergent, drug-related AEs. Eleven percent of patients had grade ≥3 treatment-emergent, drug-related AEs, with these events leading to radium-223 discontinuation in 5% of the study population.

Treatment-emergent serious AEs were experienced by 22% of patients, with 7% of patients having these lead to treatment discontinuation. Drug-related serious AEs were reported in 6% of patients, with 1% of patients discontinuing treatment due to these events.

Hematological safety data showed that abnormal neutrophil counts occurred in 5% of patients with prior taxanes and 5% of patients with no prior taxanes. Abnormal platelet counts were reported for 2% and 3% of these 2 subgroups, respectively.

Among patients with prior taxanes, 38% had received at least 1 bone marrow suppression–relevant treatment, 35% had at least 1 blood transfusion, 3% had erythropoiesis-stimulating drugs, and 3% had colony-stimulating factors. The corresponding rates in patients with no prior taxanes were 26%, 24%, 3%, and 2%, respectively.

Ten percent of patients had fractures. The fracture rate was lower in patients who received concomitant bone protective agents (BPAs) at 7% vs 12% in patients who did not receive concomitant BPAs.

Overall, there were 25 secondary primary malignancies (SPMs) occurring in 24 patients (1.6%). The most common SPMs were skin (n = 5), lung (n = 5), and bladder (n = 4). Of the 24 patients with SPMs, 67% (n = 16) had received prior radiotherapy and 4% (n = 1) had concomitant radiotherapy.

The median overall survival (OS) from the first dose of radium-223 was 15.6 months (95% CI, 14.6-16.4). The estimated OS at 2 years was approximately 30%, and the estimated OS at 3 years was approximately 17%.

“The REASSURE study supports the well-established favorable safety profile of radium-223. The incidence of secondary primary malignancies was low. The median overall survival was consistent with other real-world studies,” said Oliver Sartor, MD, medical oncologist, Division of Medical Oncology, Department of Oncology, Mayo Clinic, chair, Genitourinary Cancer Disease Group, director, Radiopharmaceutical Clinical Trials, Mayo Clinic Comprehensive Cancer Center.

REASSURE Study Background

The prospective, global, single-arm observational phase 3 REASSURE trial evaluated radium-223 use in routine clinical practice for the treatment of patients with mCRPC and bone metastases. The 1472 participants were enrolled across 20 countries, and the data cutoff date was October 24, 2024.

The median patient age was 73 years (range, 44-94). The ECOG performance score was 1 for 50% of patients, 0 for 30% of patients, and 2 or higher for 15% of patients. Metastases sites included bone only (81%), bone and lymph nodes (13%), bone and other sites (excluding lymph nodes; 4%), and bone and other sites (including lymph nodes; 2%). Overall, 19% of patients had fewer than 6 metastases, 48% had 6 to 20 metastases, 20% had more than 20 metastases but not a superscan, and 6% had more than 20 metastases with a superscan. Laboratory values showed a median PSA of 59 ng/mL (range, 0-7259), a median ALP of 133 U/L (range, 2-986), and a median LDH of 266 U/L (range, 3-2115).

Prior and concomitant therapies included abiraterone acetate (Zytiga; 48%, 15%, respectively), docetaxel (39%, 2%), enzalutamide (Xtandi; 39%, 18%), and cabazitaxel (Jevtana; 9%, 1%).

Post–radium-223 subsequent therapies received included enzalutamide (15%), abiraterone (11%), docetaxel (18%), cabazitaxel (11%), Lu-177 therapies (2%), and Ac-225 PSMA-617 (<0.1%).

The median number of radium-223 doses received was 6. Two-thirds of patients were treated with 5 or more doses of the radionuclide.

Radium-223 is approved by the FDA for the treatment of patients with CRPC, symptomatic bone metastases, and no known visceral metastatic disease.²

REFERENCES:

1. Sartor AO, Dizdarevic S, Baldari S, et al. Long-term safety of radium-223 (Ra-223) in metastatic castration-resistant prostate cancer (mCRPC): 7-year follow-up from the largest global prospective study. J Clin Oncol. 2025;43(suppl 17):5048. doi:10.1200/JCO.2025.43.16_suppl.5048

2. Bayer receives U.S. FDA approval for Xofigo® (radium Ra 223 dichloride) injection as a new treatment for castration-resistant prostate cancer with bone metastases. May 15, 2013. Accessed June 2, 2025. https://tinyurl.com/h82srftp