The role of maintenance therapy in the treatment of advanced urothelial cancer: a comprehensive systematic review and network meta-analysis

Concerns increase with maintenance therapy for advanced urothelial cancer (aUC). We perform a comprehensive network meta-analysis (NMA) to investigate the efficacy and toxicities of maintenance therapy in aUC patients. Trials assessing maintenance treatment with either a continuous or a switch strategy for aUC were identified. The primary outcome was overall survival (OS), and secondary outcome was progression-free survival (PFS) and toxicities. Nine articles reporting eight trials were included. The pooled hazard ratio demonstrated that maintenance therapy significantly improved OS giving HR 0.83 (95%CI: 0.74-0.93, P = 0.0013) and PFS with HR of 0.78 (95%CI: 0.62-0.99, P = 0.05), but increased the risk of developing severe adverse events and treated-related discontinues (P < 0.05). Sub-group analysis indicated that 'switch' ICI (immune checkpoint inhibitor) maintenance therapy significantly improved OS and PFS when compared to best support care (BSC) (P < 0.05). NMA showed that chemotherapy followed by 'switch' maintenance with ICI significantly improved OS (HR 0.70, 95%CI: 0.57-0.87) when compared to BSC. 'Continuous' maintenance with ICI alone had a tendency to improve OS (HR 0.85, 95%CI: 0.71-1.01), and TA (HR0.93, 95%CI: 0.58-1.50) and vinflunine (HR 0.74, 95%CI: 0.44-1.24) was no significantly associated with a lower likelihood of disease death. Based on the analysis of the treatment ranking, 'switch' maintenance with ICI appeared as the best treatment approach. Our pooled results confirm that maintenance therapy yields a significant survival advantage for aUC patients. NMA indicates that switch maintenance with ICI is the optimum maintenance treatment for aUC and reduces mortality by about a third.