Prognostic Impact of Bone Metastasis in Patients With Metastatic Urothelial Carcinoma Treated With Durvalumab With or Without Tremelimumab in the DANUBE Study

Abstract

Background and ObjectiveBone metastases (BM) in metastatic urothelial carcinoma (mUC) may impact patient outcomes, but their independent effect with immune checkpoint inhibitors (ICIs) is uncertain. We aimed to assess the impact of BM and PD-L1 status on outcomes in mUC patients treated with ICIs. MethodsThis post hoc analysis of the DANUBE study included 1032 mUC patients treated with durvalumab (D), D + tremelimumab (T), or standard chemotherapy (SoC). Patients were categorized by BM status and assessed for median overall survival (mOS) and median progression-free survival (mPFS) stratified by PD-L1 expression and treatment arm. Key Findings and LimitationsAmong all patients enrolled in the study, those with BM had a lower mOS than those with no BM (8.7 vs. 15.8 months; P < .0001). Patients with BM and high PD-L1 expression, treated with D or D + T, had numerically longer mOS than patients with BM and low PD-L1 expression. In contrast, in the chemotherapy arm, there was no difference in mOS for BM or no BM, based on PD-L1 expression. Patients with BM had shorter mPFS compared to no BM (2.6 vs. 5.4 months; P < .0001). The study is limited by its post hoc nature. Conclusions and Clinical ImplicationsPresence of BM was associated with worse outcomes across treatment arms. Patients with BM and high PD-L1 expression treated with D or D + T had longer mOS, suggesting potential benefits of ICIs in this subgroup. Consideration of BM and PD-L1 status in treatment decisions for mUC patients receiving ICIs may improve clinical outcomes. Plain English SummaryWe investigated the impact of bone metastases in patients with advanced bladder cancer treated with immune therapy. Patients with bone metastases had shorter survival times compared to those without. However, patients with high levels of a specific marker in their tumors had better outcomes with immune therapy. Understanding these factors could help doctors make better treatment decisions for patients with bladder cancer.