The Efficacy and Safety of Immune Checkpoint Inhibitors in Treating Advanced Urothelial Cancer: A Meta-Analysis of Clinical Trials

Background: Survival outcomes in advanced urothelial cancer (UC) is dismal. In recent years, immunotherapy remains an evolving treatment modality for those patients. We performed this meta-analysis to comprehensively evaluate the efficacy and safety of immune checkpoint inhibitors. Methods: A systematic literature review was performed through PubMed until October 2020 and a manual review of references. We calculated the pooled objective response rate (ORR), 1-year overall survival (OS) rate and 1-year progression-free survival (PFS) rate with 95% confidence intervals (95% CI) to assess the efficacy of programmed cell death receptor 1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors. Similarly, the summary associations of any-grade and grade ≥3 adverse events (AEs) were used to evaluate safety. Heterogeneity across studies was explored through stratified analyses by PD-L1 expression levels, PD-L1 or PD-1 inhibitors, drugs of study, locations of metastasis or primary tumor. Furthermore, sensitivity and publication bias analyses were conducted to assess the robustness of the association. Results: Eighteen studies comprising 3, 144 patients were included. Overall, the summary ORR of PD-1/PD-L1 inhibitors treatment was 0.20 (95% CI 0.17-0.23). Furthermore, the pooled 1-year OS and 1-year PFS rates were corresponding to 0.43 (95% CI 0.33-0.53) and 0.19 (95% CI 0.17-0.21). The summary rates of any-grade and grade ≥3 AEs were 0.66 (95% CI 0.58-0.74) and 0.13 (95% CI 0.09-0.18), respectively. Among the subgroups, PD-1/PD-L1 inhibitors had encouraging ORR in patients with lymphnode-only metastasis than those with visceral metastasis (0.41 VS. 0.17). Furthermore, the patients with the primary tumor in the lower tract had higher ORR compared with those with the primary tumor in the upper tract (0.24 VS. 0.15). Conclusion: The immunotherapy showed encouraging efficacy and acceptable safety in treating advanced UC. Furthermore, our findings provided potential clinical significance for patients with lymphnode-only metastasis or primary tumor in the lower tract. Those exciting findings need further confirmation. Funding Statement: This study was supported by the Natural Science Foundation Committee of China (NSFC 81802941) (F.L.), and the Natural Science Foundation of Guangdong Province of China (2018A0303130287) (F.L.) the Outstanding Youth Development Scheme of Nanfang Hospital, Southern Medical University (2019J009) (F.L.), Guangdong Medical Research Fund (CZ2019114 ) (L.N.H), and the Dean's research fund of Nanfang Hospital, the Southern Medical University (2019B008) (L.N.H). Declaration of Interests: The authors report no potential conflicts of interest.