Immune-related adverse events (irAEs) and the association with clinical outcomes in advanced genitourinary cancers treated with immunotherapy: A systematic review and meta-analysis.

Abstract

431 Background: The approval of several immune checkpoint inhibitors (ICIs) for the treatment of advanced genitourinary cancers has resulted in a significant revolution in the management of urological tumors. This study investigated the profile of the irAEs and evaluated the association between irAEs and clinical outcomes in the patients with advanced genitourinary cancers treated with ICIs. Methods: We conducted a comprehensive search of online databases up to April 2023 to identify eligible studies. We extracted the type, grade, and frequency of irAEs, the hazard ratios(HRs) and corresponding 95% confidence intervals (95%CIs) for overall survival (OS) and progression-free survival (PFS), raw data or the odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) for objective response rate (ORR) and disease control rate (DCR). RevMan5.3 software was used to calculate pooled results. Results: A total of 21 studies with 4779 patients were included. Of those, 13 studies investigated renal cell carcinoma (RCC), 6 studies investigated urothelial carcinoma (UC), and 2 investigated mixed population with RCC or UC. The pooled overall incidence was 29.0% (95%CI: 28.0%-30.0%) for any-grade irAEs in RCC and UC and 13.0% (95%CI: 11.0%-14.0%) for grade ≥3 irAEs. Furthermore, the HRs for OS and PFS in advanced genitourinary cancer patients with versus without irAEs were 0.45 (95%CI: 0.40-0.51, p < 0.001) and 0.41 (95%CI: 0.31-0.55, p < 0.001), respectively. The ORs for overall ORR and DCR in advanced genitourinary cancer patients with irAEs versus without irAEs were 3.65 (95%CI: 3.03-4.39, p < 0.001) and 4.19 (95%CI: 2.94-5.97, p < 0.001), respectively. In the subgroup analysis, we also observed a positive association between the occurrence of irAEs and improved treatment outcomes in UC and RCC, respectively. Specifically, patients with skin irAEs showed a better OS, patients with skin irAEs and thyroid disfunction were associated with better PFS. Conclusions: Our study provides a comprehensive overview of irAEs in advanced genitourinary cancers treated with immunotherapy. Our findings suggest that the occurrence of irAEs could be a favorable prognostic factor for advanced genitourinary cancer patients treated with ICIs.