Real-world effectiveness of Avelumab maintenance in advanced urothelial carcinoma: results from the Italian multicenter MALVA study (Meet-URO 25).

IMPORTANCE: Avelumab maintenance therapy improves survival in patients with advanced urothelial carcinoma who respond to first-line platinum-based chemotherapy. However, real-world evidence on its effectiveness and on the prognostic value of baseline clinical factors remains limited. OBJECTIVE: To evaluate the real-world effectiveness of Avelumab maintenance therapy and to identify baseline prognostic factors associated with clinical outcomes. DESIGN: Multicenter prospective observational study including a retrospective cohort of patients treated before study initiation. SETTING: Several Italian oncology centers participating between 2021 and 2023. PARTICIPANTS: A total of 251 patients with advanced or metastatic urothelial carcinoma who received Avelumab maintenance therapy after achieving disease control with first-line platinum-based chemotherapy. INTERVENTION(S) OR EXPOSURE(S): Avelumab maintenance therapy administered according to clinical practice. Baseline clinical variables, including ECOG performance status, metastatic sites, and corticosteroid use, were assessed for prognostic significance. MAIN OUTCOME(S) AND MEASURE(S): Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included overall response rate (ORR) and disease control rate (DCR). Prognostic factors were evaluated using multivariate Cox regression. RESULTS: Median OS was 22.4 months, and median PFS was 7 months. The ORR and DCR were 26.75% and 69.30%, respectively. Independent predictors of worse OS were ECOG ≥1 (HR 1.57), bone metastases (HR 1.88), brain metastases (HR 7.02), and baseline corticosteroid use (HR 2.42). An exploratory prognostic score integrating ECOG status, bone metastases, and steroid use stratified patients into three groups with significantly different outcomes: median OS was 39.9 months (no adverse factors), 14.1 months (one factor), and 8.4 months (two or more factors), with corresponding ORRs of 33.6%, 28.0%, and 6.9%. CONCLUSIONS AND RELEVANCE: In this large real-world cohort, Avelumab maintenance confirmed its effectiveness and safety in advanced urothelial carcinoma. A simple exploratory prognostic score based on ECOG performance status, bone metastases, and baseline corticosteroid use successfully stratified patients by survival outcomes and may support personalized treatment strategies in clinical practice.