Adverse events of the second-line treatment for patients with locally advanced or metastatic urothelial carcinoma of the bladder: Network meta-analysis

Aim: We aimed to compare the mortality rates related to adverse events (AEs) and discontinuation of treatment due to toxicity as well as all AEs of currently used regimens of second-line treatment strategies for advanced or metastatic urothelial carcinoma of the bladder. Methods: The MEDLINE and EMBASE databases were searched for articles according to the PRISMA extension statement for network meta-analysis. Results: Five trials comprising 2205 patients met our eligibility criteria. It is highly likely that immunotherapy, as single regimen, has the lowest rates of motor and sensory neuropathies, constipation, abdominal pain, alopecia, decreased appetite, vomiting and febrile neutropenia. Immunotherapy, in combination regimen, has the lowest rates of anemia and fatigue. Conclusion: Immunotherapy, especially as single regimen, demonstrated the highest favorable tolerability to most AEs. In the era of precision medicine, the challenge is to identify the patients who are most likely to benefit from different treatment strategies. We believe that findings of the present network meta-analysis may facilitate individualized treatment strategies based on adverse events to guide regarding the potentially best tolerated approach for patients with urothelial carcinoma of the bladder. Immunotherapy, especially as single regimen, demonstrated the highest favorable tolerability to most adverse events.