Association Between Antibiotic Therapy and Treatment Effectiveness in Patients With Renal Cell Carcinoma Receiving...

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).

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.

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).

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.