Is There a Detrimental Effect of Antibiotic Therapy in Patients with Muscle-invasive Bladder Cancer Treated with Neoadjuvant Pembrolizumab?

In locally advanced and metastatic malignancies, antibiotic (ATB) therapy has a negative effect on immunotherapy efficacy. Therefore, we aimed to evaluate whether ATB therapy and use of specific ATB classes with concomitant neoadjuvant pembrolizumab affected pathologic complete response (ypT0N0) and relapse-free survival (RFS) for patients with clinical T2–4N0M0 bladder cancer enrolled in the PURE-01 study. Of the 149 patients evaluated, 48 (32%) received any concomitant ATB therapy. The ATB class most commonly administered was fluoroquinolones (16 patients; 33%). In the ATB cohort, seven patients (15%) achieved ypT0N0 status, compared to 50 (50%; p < 0.001) in the untreated group. Moreover, ATB use was negatively associated with ypT0N0 status (odds ratio 0.18, 95% confidence interval [CI] 0.05–0.48; p = 0.001). The 24-mo RFS rate was 63% (95% CI 48-83%) in the ATB group versus 90% (95% CI 83–97) in the untreated group. We found that ATB use was associated with a higher recurrence rate (hazard ratio [HR] 2.64, 95% CI 1.08–6.50; p = 0.03). Exploratory analyses showed that fluoroquinolone use was associated with a higher recurrence rate (HR 3.28, 95% CI 1.12–9.60; p = 0.03). Our study revealed an association between ATB use and neoadjuvant immunotherapy efficacy in an intention-to-cure population, highlighting the need for future studies to better investigate this relationship. Patient summary: The efficacy of immunotherapy for cancer is influenced by several patient and tumor factors, including the use of antibiotics. We found that antibiotics taken at the same time as immunotherapy drugs were associated with lower rates of complete response and of recurrence-free survival among patients with muscle-invasive bladder cancer. These findings need to be confirmed in future studies.