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Shilpa Gupta, MD, Cleveland Clinic, Cleveland, OH, discusses recent developments in the treatment of urothelial cancer. Targeting the DNA damage response (DDR) pathway has proven ineffective in treating urothelial cancer, with several trials of PARP and ATR inhibitors producing negative results e.g., NCT02567409. Furthermore, data from the KEYNOTE-052 (NCT02335424) and KEYNOTE-361 (NCT02853305) trials has shown that PD-L1 is not a good indicator of pembrolizumab efficacy and that pembrolizumab should only be used in patients who are platinum-irresponsive; if patients are platinum-responsive, optimal treatment involves first line platinums, such as carboplatin, followed by checkpoint inhibitors or maintenance avelumab, if progression occurs or doesn’t occur, respectively. Lastly, the INDUCE-1 (NCT02723955) Phase I trial has produced promising early results on the use of the inducible T-cell co-stimulatory (ICOS) receptor agonist feladilimab to treat urothelial cancer, more Phase II trials are required to produce significant results. This interview took place at the American Society of Clinical Oncology (ASCO) 2021 Virtual Meeting.