Session: PD24: Kidney Cancer: Advanced (including Drug Therapy) II
PD24-12: Association between antibiotic therapy and treatment efficacy in renal cell carcinoma patients receiving either immune checkpoint inhibitors or tyrosine kinase inhibitors
Introduction: The gut microbiome affects response to immune checkpoint inhibition (ICI). As such, we hypothesized antibiotic therapy (ABT) would negatively affect outcomes in metastatic renal cell carcinoma (mRCC) patients receiving ICI. We investigated the association between ABT and overall survival (OS)/real-world progression free survival (rwPFS) in mRCC patients receiving ICI or tyrosine kinase inhibitors (TKIs) as a reference group. Methods: We included 5,306 patients with mRCC from the nationwide de-identified electronic health record-derived Flatiron Health database (ICI N=1805; TKI N=3501). Three-month landmark Kaplan Meier and log-rank tests were used to compare rwPFS and OS among ABT groups (3 months pre- vs 3 months post-treatment vs none). Cox models were used to investigate the association between rwPFS, OS, ABT and treatment modality. Results: 375 (20.8%) ICI and 616 (17.8%) TKI patients received ABT (p=0.005). In multivariable analysis, male gender (OR 0.771, p=0.006) and advanced age (OR 0.981, p<0.001) were associated with lower ABT use; ICI (OR 1.273, p=0.016) and poor IMDC (OR 1.528, p=0.012) were associated with higher ABT use. ABT was associated with reduced rwPFS and OS in ICI (rwPFS median: 9.0 vs 11.6 months; p = 0.014; OS median: 23.7 vs 33.6, p=0.017) and TKI recipients (rwPFS median: 7.98 vs 9.53, p=0.014; OS median: 18.5 vs 25.9, p<0.001) [Figure 1]. Post-treatment ABT was associated with reduced OS and rwPFS (OS ICI median: 22.5 vs 36.2 vs 33.6, p=0.006; OS TKI median: 17.8 vs 21.4 vs 25.9, p<0.001; rwPFS ICI median: 8.21 v 11.50 vs 11.60, p=0.006; rwPFS TKI median: 7.95 vs 8.02 vs 9.53, p=0.004) [Figure 2]. ABT was associated with reduced OS (ICI HR=1.28, p=0.018; TKI HR=1.27, p<0.001) and rwPFS (ICI HR=1.29, p=0.013; TKI HR=1.26, p=0.001) in both groups. Conclusions: We identified a negative association between ABT and OS/rwPFS in mRCC patients receiving ICI or TKI. These results support continued investigation of the gut microbiome health on RCC treatment efficacy. SOURCE OF Funding: DoD # (CA181178) Fox Core Grant # (P30 CA 006927).
