Antibiotic use and outcomes with systemic therapy in metastatic renal cell carcinoma (mRCC).

Abstract

607 Background: Antibiotic (Abx) use is shown to alter commensal gut microbiota, a key regulator of immune homeostasis. We conducted the largest investigation to date on the impact of Abx use on outcomes in mRCC patients treated with systemic agents. Methods: Two cohorts were analyzed: an institutional cohort (DFCI, n = 146) of patients receiving PD-1/PD-L1-based immune checkpoint inhibitors (ICI), and an external cohort from pooled phase II/III clinical trials (Pfizer, n = 4144) of patients treated with interferon (IFN, n = 510), mTOR inhibitors (n = 660), and VEGF inhibitors (n = 2974). Abx use was defined as Abx treatment at any time between 8-weeks pre- and 4-weeks post the start of systemic therapy. We examined the associations of Abx use and objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) using Cox/logistic regression models, adjusted for prognostic factors including risk groups. Results: In the DFCI cohort, 15% had non-clear cell histology, 43% had first-line ICI, 45% had combotherapy. Baseline characteristics were balanced between Abx users (n = 31, 21%) and non-users (p > 0.15). Abx users had a lower ORR (12.9 vs 34.8%, p = 0.026) and shorter PFS compared to non-users (Table). In the external cohort, Abx users (n = 709) had lower ORR (19.3 vs 24.2%, p = 0.005). IFN treated patients (current or prior cytokines) had worse OS if they received Abx compared to those who did not. However, there was no OS difference by Abx use in mTOR or VEGF treated patients without prior cytokines. Conclusions: Abx use was independently associated with worse outcomes in mRCC patients receiving contemporary ICI or historic cytokine immunotherapy. We hypothesize that concurrent use of Abx may reduce the efficacy of ICI due to a complex interplay with the host microbiome. [Table: see text]