Effectiveness and safety of radium-223 in men with metastatic castration-resistant prostate cancer (mCRPC): A systematic literature review of 48 real-world studies.

Abstract

81 Background: Radium-223 (Ra-223) has been approved for men with mCRPC with bone metastases since 2013. However, as the treatment landscape has significantly changed in the last decade, a comprehensive understanding of Ra-223's real-world outcomes could inform on treatment choice in routine clinical practice. This systematic literature review aims to fill this gap by summarizing the real-world (RW) effectiveness and safety in men with mCRPC treated with Ra-223. Methods: Electronic databases (PubMed, Embase, the Cochrane Library, trial registers) and the past-two years of relevant conferences were searched systematically for RW observational studies examining outcomes of Ra-223 in men with mCRPC published between 2014 and March 2024. Study results of interest included Ra-223 treatment pattern, real-world overall survival (rwOS) and progression-free survival (PFS), pain response, change in alkaline phosphatase (ALP) or prostate-specific antigen (PSA), and safety outcomes (any or grade 3+ skeletal-related events, myelosuppressive adverse events). Results: From 1085 citations identified, 48 studies with 15,368 men with mCRPC met inclusion criteria. Most studies were retrospective cohorts (n=39) from Europe (n=22) and North America (NA) (n=18), with sample size ranging from 104 to 1,628. Median age mostly ranged from 68 to 76 Ten studies reported tumor burden and included ≥ 25% of cohort with 20+ metastases. Over 50% of Ra-223 cohort received prior chemotherapy in 23 studies, and 50% received prior ARPIs in 22 studies. Most studies in NA and Europe reported ≥ 55% and 64% completion of ≥ 5 cycles of Ra-223, respectively. Earlier line, no prior chemotherapy or immunotherapy, hemoglobin and neutrophils within lower standard limit were key factors associated with completion of ≥5 cycles of Ra-223. Median rwOS varied widely from 11 to 24 months with two exceptions and nearly a 1/3 rd reporting 15 months or longer. Completion of ≥ 5 cycles was associated with a 2 to 5-fold increase in the median rwOS. PFS ranged from 4.3 to 7.3 months with a median of 2 prior lines in the 7 studies reporting. 12 studies reporting pain outcomes showed a reduction in pain with varying magnitude. Of 13 studies reporting grade 3+ myelosuppression, incidence varied from 1-22%. Out of 14 studies reporting fractures, the incidence was <10% in most studies (N=12) with trends toward lower rates with bone health agent (BHAs) use. Conclusions: This is the most up-to-date and comprehensive review of the effectiveness and safety of Ra-223 in a modern era with more widespread use of ARPIs post landmark ALSYMPCA trial for Ra-223. Findings highlight the survival benefits of early use of Ra-223 with the completion of 5 or more cycles, along with a favorable safety profile and low rates of fracture when guideline recommended BHAs are used.