Long-term data support radium-223 safety in mCRPC

Long-term results of the REASSURE trial (NCTO2141438) evaluating radium-223 (Ra-223, Xofigo) in patients with metastatic castration-resistant prostate cancer point to the agent’s strong safety profile in this patient population.¹

In a poster presentation at the 2025 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois, A. Oliver Sartor, MD, chair of the genitourinary cancer disease group and director of radiopharmaceutical clinical trials at Mayo Clinic, Rochester, Minnesota, and colleagues reported the final analyses of REASSURE, which was “a global, prospective, observational study” that “examined the long-term safety of Ra-223 in a large population of patients with metastatic castration-resistant prostate cancer,” according to the investigators. REASSURE incorporated data from 1472 patients in 20 countries who were treated with Ra-223 between 2014 and 2017. The data cut-off date was October 24, 2024. The median follow-up time was 17 months (range, 0.3-95.4 months). Short- (30 days) and long-term (7 years) safety outcomes were included in the study.

Median patient age was 73 years (minimum, 44 years; maximum, 94 years). ECOG Performance Status was 0 in 30%, 1 in 50%, and 2 or higher in 15%. Sites of metastases were bone only in 81%, bone and lymph nodes in 13%, bone and other sites (excluding lymph nodes) in 4%, and bone and other sites (including lymph nodes) in 2%. Regarding extent of metastatic disease, 19% had fewer than 6 metastases, 48% had 6 to 20 metastases, 20% had more than 20 metastases but not a Superscan, and 6% had a Superscan. Median prostate-specific antigen level was 59 ng/mL (range, 0 ng/nL-7259 ng/mL).

Six percent of patients received 1 Ra-223 injection, 7% received 2 injections, 11% received 3 injections, 9% received 4 injections, 7% received 5 injections, and 60% received 6 injections. The investigators reported that 67% of patients received at least 5 doses of Ra-223, with a median of 6 doses.

Nearly half of the cohort (48%) received abiraterone acetate (Zytiga) as a prior therapy, whereas 15% received abiraterone acetate as concomitant therapy. Thirty-nine percent and 2% received docetaxel as prior or concomitant therapy, respectively; 39% and 18% received enzalutamide (Xtandi), respectively; and 9% and 1% received cabazitaxel (Jevtana), respectively. Subsequent life-prolonging therapies included enzalutamide (15%), abiraterone acetate (11%), docetaxel (18%), cabazitaxel (11%), Lu-177 therapies (2%), and Ac-225 PSMA-617 (<0.1%).

Occurrence of any adverse event (AE) was observed in 50% of the cohort. Treatment-emergent drug-related AEs were seen in 37%, with grade 3 or higher treatment-emergent drug-related AEs seen in 11%. Treatment-emergent drug-related AEs leading to discontinuation of Ra-223 occurred in 5% of patients. Treatment-emergent serious AEs were observed in 22%, and treatment-emergent serious AEs leading to discontinuation of Ra-223 were seen in 7% of patients. Drug-related serious AEs were observed in 6% of patients, and drug-related serious AEs were seen in 1% of patients. Diarrhea (11%), anemia (9%), nausea (9%), and fatigue (8%) comprised the most common treatment-emergent drug-related adverse events.

Prior taxane use was associated with a greater utilization of bone marrow suppression treatment (38% in patients with prior taxane use vs 26% in patients with no taxane use).

In terms of hematological safety, “Prior taxanes did not increase reported hematological adverse events during treatment with Ra-223,” the investigators reported. Abnormal neutrophil counts were observed in 5% of patients who had no prior taxanes vs 5% in patients who prior taxanes, and abnormal platelet counts were observed in 2% of patients who had no prior taxanes vs 3% in patients who prior taxanes.

Receipt of bone-protective agents (BPAs) was associated with a lower incidence of fracture. Overall fracture incidence was 10% and was 12% in patients who did not receive a concomitant BPA vs 7% in those who received a BPA.

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

“The REASSURE study represents the longest follow-up of a radionuclide therapy reported to date and supports the well-established favorable safety profile of Ra-223,” the investigators wrote in their conclusion.

REFERENCE

1. Sartor O, 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