Impact of antiresorptive bone agents in hormone-sensitive metastatic prostate cancer (mHSPC): A meta-analysis.

e17122 Background: The continuous improvement of survival of mHSPC patients (pts) increases their risk of bone loss. The use of bone modifying agents (BMAs) in the mHSPC setting is still unclear. We conducted a systematic review and meta-analysis investigating the use of BMAs in men with mHSPC. Methods: We searched PubMed database, and reviewed clinical trials and reference lists of publications to identify studies comparing the use of BMA vs standard of care (SOC) in mHSPC. Retrospective studies and those lacking outcomes of interest were excluded. The co-primary outcomes were overall survival (OS) and time to the first skeletal-related event (SRE). For each study, we extracted Hazard Ratio (HR) and confidence interval (CI) for time-to-event outcomes and Relative Risk (RR) for toxicities. Effects were combined using the random-effects model. This is registered in PROSPERO, CRD42024623104. Results: Among 1733 studies identified, six were included in the analysis. No study included pts who received novel androgen receptor pathway inhibitors (ARPI) or anti-RANKL agents. For overall survival (OS), five studies (3,852 pts) were included. BMA use was associated with improved OS (HR 0.87 [95% CI 0.78 – 0.97], p = 0.009). In the skeletal-related event (SRE) analysis, six studies (3,912 pts) were included, showing that BMA delayed time to first SRE (HR 0.80 [95% CI 0.69 – 0.94], p = 0.006). In terms of safety, BMA use was not associated with an increased risk of grade ≥3 adverse events (p = 0.8) or renal dysfunction (p = 0.9). However, it significantly increased the risk of osteonecrosis (RR 6.9 [95% CI 1.25 – 37.9]). Conclusions: These findings suggest that BMAs may benefit mHSPC pts. However, their role in the ARPI era remains unclear and warrants further evaluation in future clinical trials.