Overlapping Extremes: An Analysis of Avelumab Maintenance and Pembrolizumab in Advanced Urothelial Carcinoma

Introduction: Avelumab and pembrolizumab are approved immune checkpoint inhibitors (ICIs) for advanced urothelial carcinoma (UC) that are used as maintenance and salvage therapies, respectively. The aim of this study was to highlight patterns of extreme response and support the development of biomarker-driven strategies to optimise patient selection and treatment sequencing. Methods: This was a prospective study that included 79 patients with advanced UC treated with avelumab (n = 32) or pembrolizumab (n = 47) following platinum-based chemotherapy. Outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Results: Avelumab was associated with a DCR of 84.4% and a complete response (CR) rate of 34.4%, while pembrolizumab was associated with a DCR of 55.3% and a CR rate of 12.8%. Progressive disease (PD) occurred in 15.6% and 44.7% of patients, respectively. Despite differences in treatment indications and timing, median PFS and OS in patients with CR and PD were surprisingly comparable across the two agents. Conclusions: These findings suggest that extreme responses to ICIs in advanced UC—ranging from complete response to primary progression—may occur irrespective of treatment setting, underscoring the pivotal role of tumour–immune biology. Biomarker-driven strategies are needed to optimise patient selection. Trial Registration: OBSERVE-UC study; registration ID: CEAVC 25351.