Second-Line Systemic Treatment for Metastatic Urothelial Carcinoma: A Network Meta-Analysis of Randomized Phase III Clinical Trials

Purpose: We aimed to evaluate and compare relative impacts of various second-line treatments on overall survival (OS) in metastatic urothelial carcinoma (mUC). Method: A literature search was conducted in PubMed, Embase, and the Cochrane Library for all articles published prior to December 2018 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Seven randomized controlled trials with phase III design that met study eligibility criteria were selected for final analysis. A Bayesian framework network meta-analysis (NMA) was applied to indirectly compare the effect of each treatment on OS. Results: In NMA, atezolizumab (HR, 0.90; 95% CI, 0.57–1.40) and pembrolizumab (HR, 0.77, 95% CI, 0.48–1.20) showed no significant effect on OS improvement compared to vinflunine. Gemcitabine/paclitaxel combination (HR, 1.30; 95% CI, 0.80–1.90) and lapatinib (HR, 0.95; 95% CI, 0.57–1.60) was not significantly associated with OS improvement compared to atezolizumab and best supportive care, respectively. However, results of rankograms revealed that pembrolizumab and atezolizumab were the first and second rank therapeutic agents for OS improvement in post-platinum mUC. Conclusions: Our NMA results are inconclusive. The optimal second-line treatment for OS improvement could not be determined because there were no significant OS differences among evaluated therapeutic agents. However, the use of immunotherapeutic agents such as atezolizumab and pembolizumab may have priority for improving OS in second-line setting of mUC.