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.
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.
Current oncology reports. 2018 Apr 11*** epublish ***
Vadim S Koshkin, Petros Grivas
Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Ave, Desk CA-60, Cleveland, OH, 44195, USA., Department of Medicine, Division of Oncology, Seattle Cancer Care Alliance, University of Washington and Fred Hutchinson Cancer Research Center, 825 Eastlake Ave E, MS: G4-830, Seattle, WA, 98109, USA. .