Effectiveness and safety of radium‐223 dichloride in patients with castration‐resistant prostate cancer and bone metastases in real‐world practice: A multi‐institutional study

Abstract

Objective Radium‐223 (Ra‐223) dichloride is the bone‐targeted radioligand therapy that prolongs overall survival (OS) in patients with bone‐metastatic castration‐resistant prostate cancer (CRPC). We aimed to evaluate the safety and effectiveness of this treatment in real‐world practice. Methods We included Japanese men treated with Ra‐223 for bone‐metastatic CRPC from 10 institutions, retrospectively. Primary endpoint was OS. Secondary endpoint was maximum decline of alkaline phosphatase (ALP), lactate dehydrogenase, and prostate‐specific antigen values, the rate of adverse events, and time to pathological fracture after Ra‐223 treatment. Exploratory endpoint was the associations between clinical parameters and OS. Results In total, 73 men with bone metastatic CRPC treated with Ra‐223 were enrolled. The median OS was 20.9 months. ALP levels decreased significantly from pre‐treatment (p = 0.03). Anemia occurred in three (4.1%) patients. Grade ≥ 3 non‐pathological fractures occurred in four (5.5%) men. Nine (12.3%) patients presented pathological fracture; 7/30 (23.3%) were in men without concomitant use of a bone‐modifying agent (BMA) while 2/43 (4.7%) were in patients with concomitant BMA (p = 0.03). The median OS in patients with ≥3 cycles treatment (27.2 months, p < 0.001) or hemoglobin ≥12 g/dl (27.2 months, p = 0.001) or absence of bone pain (36.3 months, p = 0.004) was significantly longer compared to those who with ≤2 cycles or hemoglobin<12 g/dl or presence of bone paint, respectively. Conclusions This study has shown the outcomes of Ra‐223 treatment in real‐world practice, where the number of treatment cycles, baseline anemia and bone pain may be useful to predict OS in Ra‐223 treatment.

Bone‐modifying agents are protective for symptomatic skeletal events in Radium‐223 treatment

“…We retrospectively included patients with CRPC and bone metastases treated with Ra‐223 between June 2016 and December 2018 from the following 10 institutions: National Hospital Organization Kyushu Cancer Center (Fukuoka), Kyushu Central Hospital (Fukuoka), Kyushu University Hospital (Fukuoka), Miyazaki Prefectural Miyazaki Hospital (Miyazaki), Harasanshin Hospital (Fukuoka), Saga‐ken Medical Centre Koseikan (Saga), and Japanese Red Cross Fukuoka Hospital (Fukuoka), as previously described 16 . We included Japanese men older than ≥20 years with a histopathological diagnosis of PC and confirmed failure of primary ADT, bone metastases, and no known visceral metastases.…”

“…Patients with CRPC and bone metastases received 4‐weekly Ra‐233 (55 kBq/kg) treatment for up to six cycles based on the recommendations of the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) for the initiation of Ra‐223 therapy. Castration status was maintained during treatment as previously described 16 . Any concomitant systemic treatment was administered at physician's discretion.…”

DNA Damage Repair Defects and Targeted Radionuclide Therapies for Prostate Cancer: Does Mutation Really Matter? A Systematic Review

“…Following the results of the ALSYMPCA trial [ 5 ], which demonstrated a survival benefit in mCRPC patients treated with [ 223 Ra]RaCl 2 ( 223 Ra-therapy) with respect to those submitted to the best standard of care, the U.S. Food and Drug Administration (FDA) approved Xofigo TM (Bayer HealthCare Pharmaceuticals Inc.), for the targeted alpha therapy (TAT) of mCRPC [ 6 ]. Since then, TAT with 223 Ra-therapy has been widely applied in clinical practice, resulting impactful on patients’ survival and quality of life [ 7 , 8 ]. Nevertheless, 223 Ra-therapy is a bone-seeking agent; therefore, its therapeutic effect is limited only to bone metastases.…”