Background: In mUC, bone metastases (BM) are associated with significant morbidity and mortality, but their independent impact on outcomes is not well established, especially in the current era of immune checkpoint inhibitors (ICIs). This post-hoc analysis assessed the impact of BM, as well as PD-L1 status (within the same BM category) on outcomes of patients with mUC treated with ICIs. Data was derived from the Phase 3 DANUBE study, which compared D, D+T, and standard chemotherapy (SoC). Methods: Patient characteristics, disease characteristics, treatments, and outcomes were collected. Patients were categorized as having BM or no BM. Outcomes included median overall survival (OS) and median progression-free survival (PFS) (in months [mo]), estimated by the Kaplan-Meier method. PD-L1 expression was assessed using the VENTANA PD-L1 (SP263) Assay. Results: Overall, 1032 patients were included; 266 had BM (D, 80; D+T, 97; SoC, 89), and 766 had no BM (D, 262; D+T, 249; SoC, 255). Among all patients, those with BM had a lower OS than those with no BM (HR, 1.67; 95% CI, 1.43-1.92; nominal P< 0.0001) when controlling for cisplatin eligibility, PD-L1 expression, presence of visceral metastases, and treatment. Similarly, patients with BM had lower PFS compared to those without BM (HR, 1.52; 95% CI, 1.30-1.75; nominal P< 0.0001) Within each treatment arm, median OS was lower for patients with BM compared to patients with no BM for all patients, regardless of PD-L1 status (Table). Patients with BM and PD-L1–high expression, treated with either D or D+T, had numerically higher median OS compared to those with PD-L1 low; this difference was also seen in patients with no BM. In contrast, there was no difference in median OS, for BM or no BM, based on PD-L1 expression for patients treated with SoC (Table). Conclusions: In this post-hoc analysis, presence of BM was significantly and consistently associated with worse outcomes in patients with mUC across all treatment arms of the DANUBE study. PD-L1–high expression was associated with higher median OS in patients treated with D or D+T, regardless of presence of BM. These data reinforce the negative prognostic impact of BM in mUC and the role for PD-L1 expression in predicting benefit for patients treated with ICIs. Funding: AstraZeneca. Clinical trial information: NCT02516241.