Immunotherapy has been used to treat bladder cancer for more than 20 years, with great success in some patients. Intravesical administration of bacillus Calmette–Guérin, or BCG, has been approved in the U.S. for stage I bladder cancer since 1990, and rates of complete response range from 55% to 70%. However, as many as 25% to 45% of patients do not respond, and an additional 40% ultimately relapse after initial response.
More recently, multiple trials have demonstrated the efficacy of immune “checkpoint inhibitors” that target a protein called programmed cell death 1 (PD-1) or its ligand, PD-L1. In the U.S., two PD-1 inhibitors (nivolumab and pembrolizumab) and three PD-L1 inhibitors (atezolizumab, avelumab and durvalumab) are approved for treatment of advanced urothelial carcinoma. In the clinical trials that led to approval of these drugs, overall response rates were 15% to 29%.
“These results demonstrate how immunogenic bladder cancers are and that you can have great success in treating some patients with immunotherapy,” says Paul Crispen, M.D., an associate professor of urology in the UF College of Medicine. “However, despite this success and the great gains we’ve made with the newer therapies, many patients fail therapy. The critical issue is trying to identify new mechanisms and new ways to improve existing immunotherapies.
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