Clinical outcomes in advanced urothelial cancer (UC) patients who experienced immune-related adverse events (irAEs) after immune checkpoint inhibitor monotherapy (ICI).

Abstract

544 Background: Immune checkpoint inhibitors (ICIs) continue to demonstrate promise in treatment of advanced urothelial carcinoma (UC). Some patients undergoing ICIs experience immune related adverse events (irAEs) and may serve as a marker of response. We investigated the relationship between irAEs and clinical outcomes in UC patients treated with ICIs. Methods: A retrospective study of 70 UC patients treated with ICI monotherapies at Winship Cancer Institute from 2015-2020 was done. Overall survival (OS) and progression-free survival (PFS), defined as time from ICI initiation to death and clinical or radiographic progression, respectively as well as clinical benefit (CB), defined as best radiographic response of complete response, partial response, or stable disease for ≥ 6 months per RECIST v1.1, were used to measure clinical outcomes. Cox proportional hazards and multivariable analyses (MVA) were used to model associations with OS and PFS. Results: Most patients were male (70%) with a median age of 68.7 years (28.0-91.0). Most patients (95%) had urothelial carcinoma and most (81%) received at least 1 prior treatment. One third of patients had ECOG PS greater than or equal to 2. Of patients that experienced an irAE (35%), the most common were dermatologic (12.9%) and arthralgia (0.5%). In addition to significantly longer treatment duration, irAE patients had significantly increased OS (HR:0.38, 95% CI:0.18-0.79, p=0.009), significantly longer PFS (HR:0.27, 95% CI:0.14-0.53, p < 0.001), and significantly greater CB (OR:4.20, 95% CI:1.35-13.06, p=0.013). Patients who experienced dermatologic irAEs had significantly increased OS, PFS, and CB (Table). Conclusions: Our results demonstrate that UC patients undergoing ICI therapy who experience irAEs, especially dermatologic irAEs, had improved clinical outcomes. This suggests that irAEs may serve as a clinical biomarker of advantageous response in patients receiving ICI. Future prospective studies are needed for validation.[Table: see text]