Antibiotic use and survival of patients receiving pembrolizumab for chemotherapy-resistant metastatic urothelial carcinoma

Objectives: The use of antibiotics alters gut microbiota and has been reported to impact outcomes in immune checkpoint inhibitor (ICI) treatment in various types of cancer. We investigated the impact of antibiotics on patients with metastatic urothelial carcinoma (mUC) treated with pembrolizumab. Materials and methods: The data of 67 patients with chemotherapy-resistant mUC who were treated with pembrolizumab were retrospectively evaluated. The patients were classified into groups according to antibiotic status (with-antibiotic and without-antibiotic), and the progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were compared between the 2 groups. Results: PFS (median: 1.1 vs. 8.9 months; P < 0.001) and OS (median: 2.3 vs. 19.5 months; P < 0.001) were significantly shorter in the with-antibiotic group (n = 15, 22%) than in the without-antibiotic group (n = 52, 78%). Patients in the with-antibiotic group had significantly higher Eastern Cooperative Oncology Group performance status scores (P = 0.042). Multivariable analyses revealed antibiotic use as an independent predictor of PFS (P < 0.001) and OS (P = 0.002). No patients in the with-antibiotic group achieved a complete response to pembrolizumab. The ORR (complete response (CR) + partial response (PR)) was higher among patients not treated with antibiotics than among patients treated with antibiotics, though the difference was not significant (34.6% vs. 13.3%, P = 0.093). The DCR (CR + PR + stable disease) was also higher among patients in the with-antibiotic group than in the without-antibiotic group (57.7% vs. 20.0%, P = 0.008). Conclusion: The use of antibiotics was negatively associated with outcomes in patients with mUC who are administered pembrolizumab. Baseline performance status was worse for these patients. Further analyses are required to identify associations between antibiotic use, bacterial infection for which it was indicated or its influence on performance status, on treatment outcomes. (C) 2021 Elsevier Inc. All rights reserved.