Evaluation of Optimal Sequential Treatment Patterns and Clinical Outcomes in Patients With Advanced Urothelial Carcinoma Treated With First‐Line Platinum‐Based Chemotherapy: A Multicenter Collaborative Study

ABSTRACT Background Few studies have provided a comprehensive analysis of sequential treatment strategies for locally advanced and metastatic urothelial carcinoma (la/mUC). This study assessed treatment patterns, prognostic factors, and optimal sequencing strategies in patients receiving first‐line platinum‐based chemotherapy (1 L‐PBC). Methods This retrospective, multicenter study analyzed 212 la/mUC patients who initiated 1 L‐PBC. Treatment sequences were categorized based on the therapy, including immune‐oncology (IO) drug and enfortumab vedotin (EV) therapy. Multivariate logistic regression identified risk factors for failing to progress to EV therapy. Results The median follow‐up duration was 17 months. Of the 212 patients, 65 (38.9%) progressed to EV therapy, achieving the longest median overall survival (OS) of 41 months, compared to 25 months in the 1 L‐PBC + IO group and 8 months in the 1 L‐PBC group. Poor performance status (ECOG‐PS ≥ 1), age ≥ 80 years, and elevated levels of C‐reactive protein (≥ 1) were significant predictors of failing to reach EV therapy. Kaplan–Meier analysis indicated no survival difference based on avelumab use in patients with no risk factors, but patients with one or more risk factors receiving avelumab had significantly longer OS than patients who did not receive avelumab. Conclusions This study emphasizes the prognostic importance of achieving EV therapy and the role of maintenance avelumab in improving outcomes for la/mUC patients with one or more risk factors after 1 L‐PBC. Combining EV with pembrolizumab is a promising first‐line treatment, and 1 L‐PBC remains a viable option for selected patients.