Prognostic Factors of Platinum-Refractory Advanced Urothelial Carcinoma Treated with Pembrolizumab.

Simple Summary: Several studies have investigated various types of biomarkers to predict responses to immune checkpoint inhibitor (ICI) therapy for patients with platinum-refractory advanced urothelial carcinoma, but they were inconclusive. Recently, antibiotic exposure has attracted attention as a biomarker because it may affect antitumor immunity through changes in gut microbiota. We evaluated the factors predictive of ICI response, including antibiotic exposure, in 41 metastatic urothelial carcinoma patients. The patients' median age was 75 years, and the vast majority of the patients were male. The objective response rate was 29.3%, with a median overall survival (OS) of 17.8 months. A high neutrophil-to-lymphocyte ratio (NLR) and poor performance status (PS) were significantly associated with poor OS. Antibiotic exposure did not have a significant impact on OS. Introduction: Immune checkpoint inhibitor (ICI) therapy has significantly improved the prognosis of some patients with advanced urothelial carcinoma (UC), but it does not provide high therapeutic efficacy in all patients. Therefore, identifying predictive biomarkers is crucial in determining which patients are candidates for ICI treatment. This study aimed to identify the predictors of ICI treatment response in patients with platinum-refractory advanced UC treated with pembrolizumab. Methods: Patients with platinum-refractory advanced UC who had received pembrolizumab at two hospitals in Japan were included. Univariate and multivariate analyses were performed to identify biomarkers for progression-free survival (PFS) and overall survival (OS). Results: Forty-one patients were evaluable for this analysis. Their median age was 75 years, and the vast majority of the patients were male (85.4%). The objective response rate was 29.3%, with a median overall survival (OS) of 17.8 months. On multivariate analysis, an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥ 2 (HR = 6.33, p = 0.03) and a baseline neutrophil-to-lymphocyte ratio (NLR) > 3 (HR = 2.79, p = 0.04) were significantly associated with poor OS. Antibiotic exposure did not have a significant impact on either PFS or OS. Conclusions: ECOG-PS ≥ 2 and baseline NLR > 3 were independent risk factors for OS in patients with platinum-refractory advanced UC treated with pembrolizumab. Antibiotic exposure was not a predictor of ICI treatment response. [ABSTRACT FROM AUTHOR]