Beta-blockers and overall survival in men receiving ADT + systemic therapy for metastatic prostate cancer.

e17112 Background: Beta-adrenergic signaling has been implicated in prostate cancer progression. However, observational studies of beta-blocker (BB) use have shown inconsistent associations with survival. We evaluated whether BB use at systemic therapy initiation was associated with overall survival (OS) in men with metastatic prostate cancer treated with androgen deprivation therapy (ADT) plus systemic therapy. Methods: Using the TriNetX network, we identified men with metastatic prostate cancer who initiated ADT and subsequently started systemic therapy with an androgen receptor signaling inhibitor (ARSI) or docetaxel. The index date was systemic therapy initiation. Patients were classified as BB users or BB nonusers based on medication exposure at the index date. Propensity score matching (1:1) was performed to balance demographics, metastatic patterns, comorbidities, and baseline laboratory values. OS was analyzed using Kaplan-Meier methods and Cox regression. A 30-day landmark analysis was performed to address early nonproportional hazards. Subgroup and active-comparator analyses were conducted. Results: Among 8,634 eligible patients, 1,238 patients were included in each group after matching. Approximately 70% of patients received an ARSI, and 30% received docetaxel as index systemic therapy. The mean age in the matched cohort was 72 years (SD: 9). Racial and ethnic distributions were similar. The cardiovascular, metabolic, and renal comorbidity burden, as well as baseline lab values were well-balanced between groups (Table 1). BB use at systemic therapy initiation was not associated with improved OS compared with no BB use (HR 1.04, 95% CI 0.91–1.18; p = 0.56). Early hazards were non-proportional, with worse early survival among BB users; however, a 30-day landmark analysis yielded similar results (HR 1.01, 95% CI 0.88–1.15; p = 0.91). Findings were consistent in the ARSI-only subgroup (HR 1.10, 95% CI 0.93–1.30; p = 0.25) and in an active-comparator analysis versus calcium channel blockers (HR 1.00, 95% CI 0.80–1.24; p = 0.97). Conclusions: In this large real-world cohort of men receiving ADT plus systemic therapy for metastatic prostate cancer, BB use at the time of systemic therapy initiation was not associated with an overall survival benefit. Overall, these results reassure that BB use is not associated with inferior overall survival in this high-risk population. Baseline characteristics after propensity score matching. Variable Beta-Blocker No Beta-Blocker Age, mean ± SD (y) 72.0 ± 9.1 72.3 ± 8.9 Race/Ethnicity, % White 67.6 69.3 Black 16.7 15.3 Hispanic 5.9 5.4 Other 9.8 10.0 Comorbidities, % Hypertension 67.2 67.2 CAD 29.4 29.4 Heart failure 14.8 14.8 Atrial fibrillation 20.8 20.8 DM 28.3 28.3 CKD 18.0 18.0 Baseline laboratory values, mean ± SD Hemoglobin (g/dL) 11.7 ± 2.4 11.5 ± 2.4 Albumin (g/dL) 3.7 ± 0.6 3.7 ± 0.6 Sodium (mmol/L) 138 ± 3.5 138 ± 3.6 PSA (ng/mL) 280 ± 970 292 ± 963