Prognostic role of baseline levels and early changes of systemic inflammatory indexes for avelumab maintenance in metastatic urothelial carcinoma: The Meet-URO25a/SAILOR study.

Abstract

e16572 Background: Avelumab maintenance after first-line platinum-based chemotherapy represents a cornerstone for the treatment of metastatic urothelial carcinoma (mUC). However, identifying prognostic biomarkers is paramount for optimizing patients’ benefits while minimizing toxicity. Systemic inflammatory indexes have been studied as prognostic biomarkers for immune checkpoint inhibitors in many tumor types, but their role in mUC is still debatable. We hypothesized that systemic inflammatory indexes could be correlated with survival in mUC patients treated with maintenance avelumab. Methods: Meet-URO25 is a multicenter Italian prospective/retrospective registry of mUC patients treated with first-line avelumab maintenance from 01/2021 to 12/2024. In the SAILOR/Meet-URO25a sub-analysis, we investigated the correlation with overall survival (OS) of five inflammatory indexes (neutrophil-to-lymphocyte ratio [NLR], lymphocyte-to-monocyte ratio [LMR], platelet-to-lymphocyte ratio [PLR], neutrophil-to-eosinophil ratio [NLR], and systemic-inflammation-index [SII]) at baseline and after 3 cycles of avelumab. ROC curves with Youden’s test, the Kaplan-Meier method with log-rank test, and Cox regression analyses were used. Results: 258 patients (106 female; median age: 63yrs) were included in the analysis. Low baseline NLR (Hazard ratio [HR] 0.37; 95% confidence interval [CI] 0.19-0.73; p: 0.016) and SII (HR 0.75; 95%CI 0.52-0.98; p: 0.033) were associated with better OS. After 3 cycles of therapy, decreasing NLR (HR 0.64; 95%CI 0.43-0.94; p: 0.02), NER (HR 0.67; 95%CI 0.46-0.99; p: 0.006) and SII (HR 0.55; 95%CI 0.37-0.81; p: 0.002) were significantly associated with longer OS. In the multivariate analysis, the presence of liver metastases, response both to first-line chemotherapy and avelumab, baseline NLR, early NLR and NER reduction were independent predictors of OS. Conclusions: Our results suggest that baseline levels of NLR and systemic inflammatory indexes and their kinetics after avelumab initiation may be prognostic in pts with mUC. The combined evaluation of systemic inflammatory indexes and their early changes should be further investigated to obtain additional prognostic or predictive value.