Introduction: Several immune checkpoint inhibitors (ICIs) have been approved for the treatment of advanced genitourinary cancers. However, there is an unmet need to identify predictors for the efficacy of ICIs. In this study, we conducted a systemic review and meta-analysis to evaluate the association between immune-related adverse events (irAEs) and clinical outcomes in advanced genitourinary cancers treated with immunotherapy.
Methods: Databases of MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched for eligible studies. Raw data for objective response rate (ORR), number of patients, hazard ratios (HRs), and corresponding 95% confidence intervals (95%CIs) for progression-free survival (PFS) and overall survival (OS) were extracted. Meta-analysis was performed using Review Manager 5.3.
Results: A total of 10 studies involving 2933 patients were included, in which 6 studies reported data of renal cell carcinoma (RCC), 3 reported data of urothelial carcinoma (UC), and 1 reported data of mixed population with RCC or UC. Overall, patients with irAEs were associated with significantly higher ORR (odds ratio [OR]: 3.37; 95%CI: 2.69–4.23; P<0.00001), longer PFS (HR: 0.39; 95%CI: 0.31–0.50; P<0.00001), and OS (HR: 0.50; 95%CI: 0.42–0.59; P<0.00001) in patients with advanced genitourinary cancers. More specifically, similar results were observed in patients with RCC that irAEs predicted better ORR (OR: 3.89; 95%CI: 2.36–6.40; P<0.00001), PFS (HR: 0.39; 95%CI: 0.30–0.50; P<0.00001), and OS (HR: 0.48; 95%CI: 0.35–0.65; P<0.00001). For patients with UC, irAEs were associated with higher ORR (OR: 3.15; 95%CI: 2.41–4.12; P<0.00001) and improved PFS (HR: 0.41; 95%CI: 0.18–0.93; P=0.03), while the relationship between the presence of irAEs and OS was not statistically significant (HR: 0.28; 95%CI: 0.06–1.26; P=0.10).
Conclusions: IrAEs were associated with better clinical outcomes in patients with advanced genitourinary cancers receiving ICIs, especially in patients with RCC.