Incidence of immune-related adverse events (irAEs) and treatment discontinuation rates (TDR) in the adjuvant and metastatic setting in patients with urological malignancies: A systemic review and meta-analysis.

Abstract

716 Background: Immune checkpoint inhibitors (ICI) are the standard treatment for numerous cancer types, in both the metastatic (MET) and adjuvant (ADJ) settings. Cancer induces an immunosuppressive effect not only in the tumor but also systemically. In patients (pts) with localized cancer, the surgical removal of the tumor can potentially restore immune system function (Allen, Nat Med 2020); however, this immune system reactivation may paradoxically place these pts at higher risk for irAEs. This study aimed to compare the incidence of irAEs and TDR in ADJ and MET urological cancers. Methods: A systematic review and meta-analysis of tumors treated with ICI was conducted. Herein we analyzed anti-PD-1/PD-L1 genitourinary (GU) clinical trials (CT) published until December 2024 that reported irAEs, treatment-related AEs (TRAEs) or AEs. CT of neoadjuvant therapies, radiotherapy or combination regimens were excluded. Primary outcomes were incidence of irAEs and TDR. Data were analyzed using random-effects model and heterogeneity was assessed with I². Summary measures are presented as proportions with 95% confidence intervals. The study protocol was registered with PROSPERO (CRD42024590667). Results: We identified 209 records, of which 39 CT (6 and 33 in the ADJ and MET setting, respectively) met the inclusion criteria (8904 pts). 14 CT reported irAEs (3508 pts). The incidence of all-grade irAEs in the ADJ setting was 45.3% and 28.6% in the MET setting (p = 0.03). No differences were shown in grade 3 or higher (g3+) irAEs (9.6% vs. 8.4%). TDR due to AEs (16.5% vs. 11.4%, p = 0.008) and TRAEs (15.5% vs. 6.5%, p < 0.001) was higher in the ADJ setting. The incidence of all-grade TRAEs was higher in the ADJ setting (76% vs. 69.7%, p = 0.03) but no differences were found in g3+ TRAEs (16.8% vs. 18.2%) or all-grade AEs (96.5% vs. 94.6%). g3+ AEs were higher in the MET setting (37.8% vs. 51.9%; p = 0.002). Conclusions: GU cancer pts had higher incidence of irAEs and TDR in the ADJ setting vs. MET pts, potentially due to restoration of the immune system after tumor resection. Further research is needed to explore the interplay among immune system function in cancer pts, ICI, and irAEs.