Real-world safety and effectiveness of radium-223 in Japanese patients with castration-resistant prostate cancer (CRPC) and bone metastasis: exploratory analysis, based on the results of post-marketing surveillance, according to prior chemotherapy status and in patients without concomitant use of second-generation androgen-receptor axis-targeted agents

Abstract

Background Based on results from Japanese post-marketing surveillance, exploratory analyses were performed to investigate real-world outcomes of radium-223 for metastatic CRPC (mCRPC) according to patient characteristics. Methods This non-interventional, prospective study enrolled mCRPC patients selected for radium-223 treatment in clinical practice. Six-month safety and effectiveness were evaluated in subgroups who had/had not received prior chemotherapy (prior-chemo/no prior-chemo groups), and a subgroup who had not received concomitant androgen-receptor axis-targeted agents (ARATs). Results In the overall population (n = 296), the prior-chemo group (n = 126) tended to have more bone metastases, more analgesic use, and higher prostate-specific antigen values than the no prior-chemo group (n = 170). Incidences of treatment-emergent adverse events (TEAEs), drug-related TEAEs, and ≥ grade 3 drug-related hematological TEAEs were 47% vs. 53%, 25% vs. 29%, and 4% vs. 7% in the no prior-chemo and prior-chemo groups, respectively. Incidences of TEAEs (61%), drug-related TEAEs (36%), and ≥ grade 3 drug-related hematological events (12%) were numerically higher in 33 patients who had received two lines of prior chemotherapy. Multivariate analysis showed that two lines of prior chemotherapy, and hemoglobin, platelet, and lactate dehydrogenase values were baseline factors significantly related to ≥ grade 2 platelet count decreased. Safety and effectiveness in patients without concomitant ARATs (n = 201) were similar to those in the overall population. Conclusion In a real-life setting, radium-223 was well tolerated irrespective of prior chemotherapy, but relatively higher incidences of TEAEs and hematotoxicities were suggested in patients with two lines of prior chemotherapy, possibly reflecting more advanced disease. Radium-223 safety and effectiveness in patients without concomitant ARATs were favorable.

Administration of radium‐223 and the prognosis in Japanese bone metastatic castration‐resistant prostate cancer patients: A large database study

“…While there have been many reports on patients treated with Ra‐223 in Japan, none have described the improvement in the OS with Ra‐223 compared with a cohort not treated with Ra‐223 (Table 2). 5–12 Therefore, in the present study, we investigated whether or not Ra‐223 improves the OS in Japanese patients using a large‐scale healthcare fee database.…”

“…In contrast, in Japan, all CRPC patients with bone metastases can be treated with Ra‐223. To complete six courses of Ra‐223 and thereby obtain an OS benefit, not a few bone metastatic CRPC patients in Japan receive Ra‐223 without waiting for two or more new AR inhibitors or DOC 7,10 . While there have been many reports on patients treated with Ra‐223 in Japan, none have described the improvement in the OS with Ra‐223 compared with a cohort not treated with Ra‐223 (Table 2).…”

“…Ra‐223 is widely used in daily clinical practice in Japan for bone metastatic CRPC, with a total of 5852 vials administered annually in 2018 4 . There were several studies to confirm that completion of six‐course Ra‐223 showed longer survival compared to the one‐ to five‐course group and examined the factors who showed longer prognosis who received Ra‐223 in Japanese patients 5–14 . However, almost all studies of Ra‐223 from Japan have used patient cohorts receiving Ra‐223, with no non‐Ra‐223 induction patient cohorts included 2,5,7,10,11 …”

Real-world effectiveness, long-term safety and treatment pathway integration of radium-223 therapy in patients with metastatic castration-resistant prostate cancer

“…RWE suggests that 223 Ra is generally well tolerated, irrespective of prior chemotherapy status, although prior chemotherapy may be associated with an increased likelihood of hematological events ( 52 , 53 ), possibly due to patients having more advanced disease (e.g., bone marrow involvement) and/or prior chemotherapy toxicities.…”

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with prostate cancer

“…The safety and effectiveness of Ra-223 in patients without concomitant use of ADT were encouraging, and similar to those in the overall population. 120 However, due to the fact that Ra-223 has been associated with an increased incidence of fractures in combination with AAP in the ERA trial, 121 its use in Europe has been restricted to patients who have received at least two lines of systemic therapy for CRPC (abiraterone/enzalutamide and docetaxel) or who are ineligible to receive these therapies. 122 Administration of Ra-223 in combination with AAP is not permitted.…”