Denosumab versus zoledronic acid in patients with breast cancer: A propensity-matched real-world time-to-event analysis.

12079 Background: Bone-modifying agents are routinely used in patients with breast cancer to reduce skeletal-related complications and metabolic disturbances. Denosumab and zoledronic acid are commonly prescribed; however, comparative real-world data evaluating their relative safety and effectiveness remain limited. We compared time-to-event outcomes associated with denosumab versus zoledronic acid in a large real-world cohort of patients with breast cancer. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network, comprising electronic health records from 70 healthcare organizations. Adult patients with breast cancer who received either denosumab or zoledronic acid were identified, excluding those with underlying osteoporosis. Patients were propensity score–matched 1:1 based on demographics, comorbidities, concomitant oncologic therapies, and baseline laboratory parameters, yielding 15,147 patients per cohort. Outcomes assessed over a 5-year follow-up period included time to hypercalcemia, severe hypercalcemia (serum calcium ≥14.0 mg/dL), hypocalcemia, pathological fracture in neoplastic disease, and bone pain. Time-to-event analyses were performed using Kaplan–Meier methods and compared with log-rank testing; hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated. Results: After propensity score matching, 15,147 patients were included in each cohort with well-balanced baseline characteristics. Over 5 years of follow-up, hypercalcemia did not differ between patients treated with zoledronic acid and denosumab (hazard ratio [HR] 0.99, 95% CI 0.88–1.10; log-rank p = 0.831). Severe hypercalcemia (serum calcium ≥14.0 mg/dL) was uncommon, with no significant difference between groups (HR 1.25, 95% CI 0.94–1.68; log-rank p = 0.129). Pathological fracture in neoplastic disease occurred less frequently in the zoledronic acid cohort, although this difference did not reach statistical significance (HR 0.88, 95% CI 0.76–1.01; log-rank p = 0.060). Hypocalcemia was significantly less frequent among patients receiving zoledronic acid compared with denosumab (HR 0.44, 95% CI 0.40–0.49; log-rank p < 0.001). Bone pain did not differ significantly between treatment groups (HR 0.95, 95% CI 0.89–1.02; log-rank p = 0.186). Conclusions: In this real-world analysis of patients with breast cancer, denosumab and zoledronic acid demonstrated similar time-to-event outcomes for hypercalcemia, severe hypercalcemia, pathological fracture, and bone pain, while zoledronic acid was associated with a significantly lower risk of hypocalcemia. These findings highlight important distinctions in toxicity profiles between agents and may inform individualized selection of bone-modifying therapy. Prospective studies are warranted to further define optimal agent selection in specific clinical subgroups.