Introduction: Research suggest ABT-induced dysbiosis impacts responses to immune checkpoint inhibitors (ICI) therapy. We investigated the association between ABT and overall survival (OS) and real-world progression free survival (rwPFS) in patients with metastatic urothelial carcinoma (mUC) receiving either ICI or non-ICI (cisplatin-based chemotherapy) as a reference group. Methods: We included 5,622 patients with mUC from the nationwide Flatiron Health electronic health record -derived de-identified database (ICI N=1483; non-ICI N=4139). rwPFS and OS were calculated from treatment initiation to date of real-world progression/death. 3-month landmark Kaplan Meier methods and log-rank tests were used to estimate and compare rwPFS and OS between patients with ABT who received ICI and non-ICI. Cox proportional models were used to investigate the association between rwPFS, OS, and antibiotic use, and treatment modality, adjusting for patient characteristics. Results: 407 (27.4%) ICI and 1523 (36.8%) non-ICI patients received ABT (p < 0.001). ICI (OR 0.704, p<0.001) and older age (OR 0.979, p<0.001) were associated with lower ABT use in multivariable analysis. The association between ABT and rwPFS and OS were not significantly different between ICI (rwPFS p=0.43; OS p=0.07) and non-ICI groups (rwPFS p=0.60; OS p=0.99; Figure 1). Timing of ABT as associated with reduced OS in ICI-recipients who received post-treatment ABT (ICI median: pre- 17.0 vs post- 10.9 vs none- 16.0; p = 0.005) while rwPFS was not statistically impacted by timing of antibiotic in either group (ICI p=0.22; non-ICI p=0.84; Figure 2) In multivariable analysis, ABT was associated with OS in the ICI cohort only (HR 1.228, p=0.022). Conclusions: This study identifies an ICI-specific potential negative effect of ABT on OS in patients with mUC. These results support continued investigation of the gut microbiome health on UC treatment efficacy and emphasize the importance of antibiotic stewardship. SOURCE OF Funding: DoD # (CA181178) Fox Core Grant # (P30 CA 006927)
