Real-world studies underline safety, efficacy of radium-223 in mCRPC

A literature review of nearly 50 studies has underlined the safety and efficacy of radium-223 (Ra-223, Xofigo) treatment for metastatic castration-resistant prostate cancer (mCRPC).

Rana R. McKay, MD, FASCO

“[Ra-223] has been shown to prolong overall survival (OS), improve quality of life, and delay skeletal events, with a favorable safety profile.²…Real-world studies are needed to systematically summarize the outcomes of Ra-223 monotherapy and its combination with [androgen receptor pathway inhibitors] or chemotherapy within the evolving treatment landscape,” the authors wrote in their poster from the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California. The authors were led by Rana R. McKay, MD, FASCO, a professor of medicine and urology at the University of California, San Diego.

To this end, the investigators conducted a systematic literature review of real-world observational studies of Ra-223. Eligible studies included retrospective, prospective, or cross-sectional observational studies of adult men with mCRPC who were treated with Ra-223. Studies were excluded if they had fewer than 100 participants or were randomized controlled trials, case reports, reviews, genetic studies, surveys, or consensus reports. The investigators searched Embase, PubMed, and the Cochrane Library for published studies between March 4, 2014, and March 4, 2024 using the keywords “prostate cancer,” “metastases,” and “Ra-223.” Their search retrieved 1085 citations, of which 48 met the inclusion criteria. Thirty-nine studies were retrospective. Thirty-six were multicenter and 12 were single center. Most of the studies (22) were conducted in Europe, 18 were conducted in North America, and 5 were conducted in Asia. A total of 15,768 men were included in the studies, with sample size ranging from 104 to 1628. Median age, which was reported in 37 studies, ranged from 65 to 76 years, although 1 study reported an average age of 85 years.

According to the investigators, in most studies, the overall treatment completion rates were 65% for at least 5 cycles of Ra-223 and 54% for 6 cycles. Completion of 5 or more cycles was observed in at least 50%, 55%, and 65% studies in North America, Europe, and Asia, respectively. Completion of 6 or more cycles was observed in at least 50%, 55%, and 55% of studies in North America, Europe, and Asia, respectively. The investigators reported that low alkaline phosphatase (ALP) and normal hemoglobin levels “were frequently associated with higher treatment completion.”

A total of 37 studies included real-world OS as an outcome; in these studies, median real-world OS ranged from 9 months to 23.5 months and was at least 12 months 30 (81%) studies and at least 14 months in 17 (46%) studies. Regarding real-world progression-free survival, this ranged from 4.3 months to 7.3 months in 7 studies.

A total of 12 studies reported pain outcomes, with most of the studies demonstrating approximately 49% or greater decline or control in pain following treatment with Ra-223. In studies reporting ALP outcome, at least 66% showed decline in ALP from baseline. In addition, for most studies, at least 49%, 44%, and 22% of patients had at least a 25%, 30%, and 50% decline in ALP, respectively. Also in most studies, at least 20% had any reduction in PSA level from baseline, and at least 14% had at least 30% and 50% decline in PSA from baseline.

Regarding skeletal-related events (SREs), 25% or fewer patients “had any or specific SREs in 18 of 21 studies, with lower frequencies with concurrent bone health agent (BHA) use. Studies reporting higher incidence of SREs also had higher baseline SRE events prior to Ra-223 initiation and a lower BHA use,” wrote the authors in their poster. The most common features of SREs were radiation to bone, fracture or spinal cord compression, and bone surgery.

Regarding myelosuppressive events, the rate of any-grade myelosuppressive events was 15% or lower in 13 of 15 studies, and a 1%-5% incidence of grade 3-4 myelosuppressive events. The most common myelosuppressive events included anemia, thrombocytopenia, and neutropenia.

In their poster, the authors concluded that the study’s results “highlight the survival benefits of early-use Ra-223 with completion of [at least] 5 cycles, a favorable safety profile, and low rates of fracture when guideline-recommended BHAs are used.”

REFERENCES

1. Lunan-Taylor M, Raval AD, Phan NTN, Korn MJ, Quintero V, McKay RR. Effectiveness and safety of radium-223 in men with metastatic castration-resistant prostate cancer (mCRPC): A systematic literature review of 48 real-world studies. J Clin Oncol 43, 2025 (suppl 5; abstr 81). doi:10.1200/JCO.2025.43.5_suppl.81

2. Parker C, Heidenreich A, Nilsson S, Shore N. Current approaches to incorporation of radium-223 in clinical practice. Prostate Cancer Prostatic Dis. 2018;21(1):37-47. doi:10.1038/s41391-017-0020-y.