Impact of duration of bone-targeting agent on adverse events (AEs) and skeletal-related events (SRE) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223): Real-world experience from Princess Margaret Cancer Centre (PM).

Abstract

e17052 Background: Bone-targeting agents (BTAs) are guidelines-recommended to reduce SREs in patients with mCRPC and bone metastases. Despite this, BTAs remain underutilized, and the optimal duration of therapy remains undefined. This knowledge gap is particular relevant for patients with mCRPC receiving Ra-223, who are at high risk for SREs. Methods: Patients with mCRPC and bone metastases treated with Ra-223 at PM between 2015 and 2024 were retrospectively reviewed. We evaluated the association between BTA duration (categorized as ≤2 versus >2 years), BTA-related adverse events (AEs) leading to discontinuation, and SREs (defined as compression, pathological fracture, or bone metastases requiring radiotherapy or surgery). Results: Among 252 patients treated with Ra-223, 115 (45.6%) received BTAs with evaluable duration data. Ra-223 was administered for a median of 5 cycles (range 1-6). Median age was 73.6 years (range 51.5-93.4), median baseline PSA was 38.0 ng/mL (range 0.4-6277.0) and 65 patients (57.0%) presented with de novo metastases. All patients received prior androgen receptor pathway inhibitor therapy, 45.2% had prior Docetaxel. After a median follow-up of 20.4 months (range 1.2-60), median overall survival was 19.2 months (95%CI 16.6-23.3). Of 115 patients, 40 (34.8%) received zoledronic acid, 69 (60.0%) denosumab and 6 (5.2%) both. Median BTA duration was 20.4 months (range 0.3-115.2). BTA discontinuation occurred in 110 patients (95.7%), with AEs accounting for 37.2% (Table). Compared to ≤2 years, BTA duration >2 years was associated with numerically higher but non-signficant rates of AEs leading to discontinuation (34.9% vs 40.4%). Numerically higher SREs rates (57.6% vs 65.3%) in patients who received BTAs >2 years reflected a greater cumulative risk of SREs over time. Conclusions: In patients with mCRPC treated with Ra-223, BTAs were underutilized, BTA discontinuation due to AEs were frequent, while SRE rates remained high. Within the limitation of sample size, BTA duration >2 years was associated with numerically higher but non-significant increase in AE-related discontinuation. These findings support BTA use beyond 2 years in selected high-risk patients, however highlight the need for AE management and future prospective studies to define the optimal BTA duration. BTA duration p -value Reason for BTA discontinuation ≤2yrsn=63 (%) >2yrsn=47 (%) 0.74 AEs Hypocalcemia Anemia Osteonecrosis of jaw Bone pain Osteomyelitis Renal dysfunction 22 (34.9%) 11 (16.7%) 1 (1.5%) 4 (6.1%) 4 (6.1%) 1 (1.5%) 1 (1.5) 19 (40.4%) 7 (14.3%) 0 (0%) 5 (10.2%) 4 (8.2%) 3 (6.1%) 0 (0%) Disease progression / best supportive care 35 (55.6%) 21 (44.6%) Death 4 (6.3%) 4 (8.5%) Other 2 (3.2%) 3 (6.4%)