Radium-223 re-treatment is safe in patients with mCRPC

Re-treatment with radium-223 (Xofigo) is safe in patients with metastatic castration-resistant prostate cancer (mCRPC), investigators reported at the 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium in San Francisco, California.¹

Maarten van der Doelen, MD, PhD

In their poster, the investigators, led by Maarten van der Doelen, MD, PhD, urology resident at Canisius Wilhelmina Ziekenhuis in Nijmegen, Netherlands, explained that following an initial treatment course of 6 Ra-223, the treatment may be repeated.² In the study presented at ASCO GU, the authors wrote in their poster that they sought “to evaluate the safety and efficacy of Ra-223 retreatment in [patients with] mCRPC in daily practice.”

The investigators conducted a multi-institutional retrospective cohort study. Patients with bone metastatic CRPC who had previously received 6 consecutive injections of Ra-223 and at least 1 Ra-223 re-treatment injection between 2014 and 2024 were included in the study. Patients with visceral metastases were excluded from the study. The primary end point was hematological and non-hematological adverse events (AEs), including skeletal-related events, that occurred up to 30 days following the last Ra-223 injection. Secondary end points included number of administered Ra-223 re-treatment injections, overall survival (OS) from the start of Ra-223 re-treatment, and alkaline phosphatase (ALP) and prostate-specific antigen (PSA) responses. Exploratory end points included “variables associated with ALP response during re-treatment, completion of Ra-223 retreatment, and [OS],” the authors wrote in their poster.

A total of 61 patients were included in the study. Median patient age was 75 years (interquartile range [IQR],70-79 years), and median number of prior therapies was 3 (IQR, 1-5). Twenty-seven (44.3%) patients received prior taxane-based chemotherapy, and 53 (86.9%) had received prior abiraterone acetate (Zytiga) or enzalutamide (Xtandi). Extent of bone metastases was low volume (< 6 metastases) in 8 (14.3%) patients, intermediate volume (6-20 metastases) in 31 (55.4%) patients, and high volume (>20 metastases) in 17 (30.4%) patients. Lymph node metastases were present in 17 (30.4%) patients. Baseline performance status was ECOG 0-1 in 43 (79.6%) patients and 2-3 in 11 (20.4%) patients. Median baseline PSA was 125 μg/L (IQR, 31 μg/L-248 μg/L), and median baseline ALP was 109 U/L (IQR, 173 U/L-240 U/L).

Regarding hematological AEs, 54 (91.5%) patients experienced anemia, with 1 (1.7%) patient experiencing grade 3 anemia. Twenty (33.9%) patients experienced thrombocytopenia, with 3 (5.1%) patients experiencing grade 3 thrombocytopenia. Thirty-six (61.0%) patients experienced leukopenia, with 4 (6.8%) patients experiencing grade 3 leukopenia. Twenty-seven (45.8%) patients experienced neutropenia, with 1 (1.7%) patient experiencing grade 3 neutropenia.

Non-hematological AEs included fatigue, nausea/vomiting, diarrhea, and bone pain. Fifteen (24.6%) patients experienced fatigue, with 1 (1.6%) experiencing grade 3 fatigue. Twenty (32.8%) patients experienced nausea/vomiting, with 3 (4.9%) patients experiencing grade 3 nausea/vomiting. Sixteen (26.2%) patients experienced diarrhea; no patient experienced grade 3 diarrhea. Eighteen (29.5%) patients experienced bone pain; no patient experienced grade 3 bone pain. In addition, 3 (4.9%) patients experienced bone fracture; no patient experienced a grade 3 bone fracture.

The investigators reported an OS of 16.9 months (95% CI, 11.9-21.9). Median number of re-injections was 6 (range, 1-12). ALP decline of greater than 30% was reported 33 (55.9%) patients, and PSA decline greater than 30% was reported in 7 (11.9%) patients.

“Radium-223 re-treatment was safe, with low incidence of hematologic and non-hematologic adverse events, including skeletal-related events. The high number of administered injections and the high ALP and PSA response rates suggest benefit in this cohort of [patients with] advanced mCRPC,” the authors wrote in their poster.

REFERENCES

1. van der Doelen M, van Riel J, Donswijk M, et al. Re-treatment of metastatic castration-resistant prostate cancer patients with radium-223 therapy in daily practice. J Clin Oncol 43, 2025 (suppl 5; abstr 183). doi:10.1200/JCO.2025.43.5_suppl.183

2. Sartor O, Heinrich D, Mariados N, et al. Re-treatment with radium-223: first experience from an international, open-label, phase I/II study in patients with castration-resistant prostate cancer and bone metastases. Ann Oncol. 2017;28(10):2464-2471. doi:10.1093/annonc/mdx331