JCO Oncol Pract. 2026 Apr 29:OP2500963. doi: 10.1200/OP-25-00963. Online ahead of print.
ABSTRACT
PURPOSE: It has been theorized that antibiotic therapy (ABT) affects response to immune checkpoint inhibition (ICI) by inducing dysbiosis of the gut microbiome (GM). To investigate the association between ABT and real-world overall survival (rwOS)/progression-free survival (rwPFS) in patients with metastatic renal cell carcinoma (mRCC) receiving ICI versus tyrosine kinase inhibitors (TKIs).
METHODS: In total, 5,237 patients with mRCC from a nationwide electronic health record-derived deidentified database who received ICI or TKI first-line after diagnosis were included. ABT exposure was stratified by exposure (yes or no), timing (before v after treatment initiation v none), excretion modes (hepatic v renal excretion v none), and administration routes (oral v intravenous v none). Three-month landmark Kaplan-Meier estimation and log-rank tests were used to compare rwOS/rwPFS among ABT groups. Multivariable Cox proportional hazards models with time-varying coefficients investigated the association between rwPFS, rwOS, ABT, and treatment modality.
RESULTS: ABT exposure was negatively associated with rwOS/rwPFS in both ICI (rwOS [23.9 v 33.6 months, P = .029]; rwPFS [8.8 v 11.6 months, P < .001]) and TKI (rwOS [17.4 v 26.2 months, P < .001]; rwPFS [8.0 v 9.7 months, P < .001]) recipients. For ICI patients only, a negative correlation between ABT after treatment initiation (rwOS, P = .003, rwPFS <0.001) and oral administration route (rwOS P = .004, rwPFS P = .001) was identified. In time-varying Cox proportional models, the effect of ABT on rwPFS beyond 12 months was only statistically significant in ICI patients (ICI, hazard ratio [HR], 1.67, P = .013; TKI, HR, 0.95; P = .7).
CONCLUSION: In our observational study, we identified a potential unique and complex association between ABT and rwOS/rwPFS in patients with mRCC receiving ICI. We found a negative correlation between ABT use after treatment initiation or via the oral route on oncologic outcomes in ICI patients. Moreover, there appears to be an ICI-specific negative association of ABT on rwPFS beyond 1 year. Our findings are associative, but they emphasize the importance of antibiotic stewardship in this space.
PMID:42054627 | DOI:10.1200/OP-25-00963
