The immune‐related adverse events paradox in locally advanced or metastatic urothelial cancer after atezolizumab immunotherapy: analysis of individual patient data from IMvigor210 and IMvigor211 trials

Objective To investigate the association between immune‐related adverse events (irAEs) and oncological outcomes in patients with advanced urothelial cancer receiving immune checkpoint inhibitors (ICIs), and whether the administration of systemic corticosteroids diminishes therapeutic impact. Patients and Methods The association between irAEs occurrence and clinical progression‐free survival (PFS), overall survival (OS), and cancer‐specific survival (CSS) was tested by means of multivariable Cox or competing‐risks regression, when appropriate. Patients experiencing irAEs were further stratified based on systemic corticosteroids administration. A sensitivity analysis was conducted by repeating all the analyses with median time to irAE as landmark point. Results We relied on individual participant data from two prospective trials for advanced urothelial cancer: IMvigor210 and IMvigor211. A total of 896 patients who received atezolizumab for locally advanced or metastatic urothelial cancer were considered. Overall, irAEs were recorded in 195 patients and the median time to irAEs was 64 days. On multivariable analysis, irAEs were inversely associated with the risk of disease progression (hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.40–0.61; P