PURPOSE OF REVIEW: Advanced urothelial carcinoma (aUC) has long been treated 
preferably with cisplatin-based chemotherapy, but many patients are 
cisplatin-ineligible whereas for those who progress on a platinum-based regimen 
treatment options are limited. We review key recent data regarding immune 
checkpoint inhibitors that are changing this treatment landscape.
RECENT FINDINGS: Since May 2016, five different agents targeting the PD-1/PD-L1 
pathway (atezolizumab, pembrolizumab, nivolumab, avelumab, durvalumab) have 
received FDA approval for the treatment of aUC in the platinum-refractory 
setting, while pembrolizumab and atezolizumab are FDA-approved for 
cisplatin-ineligible patients in the first-line setting. Clinical outcomes and 
safety profiles of these agents appear relatively comparable across separate 
trials; however, only pembrolizumab is supported by level I evidence from a 
large randomized phase III trial showing overall survival benefit over 
conventional cytotoxic salvage chemotherapy in the platinum-refractory setting. 
Pembrolizumab has the highest level of evidence in platinum-refractory aUC, 
whereas pembrolizumab and atezolizumab have comparable level of evidence in the 
frontline setting in cisplatin-ineligible patients. Ongoing research is 
evaluating novel agents, various rational combinations, and sequences, as well 
as predictive and prognostic biomarkers.