Immunotherapy in Bladder Cancer

Background: Bladder cancer is the fifth most common cancer in the United States. Cisplatin-based chemotherapy is the current standard of care in stage IV bladder cancer. It has increased overall survival but rarely results in complete remission, with an overall survival of 14–15 months. The most significant breakthrough in cancer therapy over the last decade was the development of immunotherapy. Data sources: KEYNOTE-045, IMvigor211, CheckMate275, Javelin Solid Tumor, MEDI4736, and KEYNOTE-0528 clinical trials. Areas of Uncertainty: There are ongoing clinical trials using combination of immunotherapy and chemotherapy as first line of therapy in the setting of metastatic urothelial cancer and also to determine the duration of treatment. Therapeutic Advances: Immunotherapy is approved as a second-line treatment for metastatic urothelial cancer. Their use as a first-line agent is only limited to patients who are ineligible for cisplatin-based treatments. Five drugs are approved by Food and Drug Administration for metastatic urothelial cancer including 3 Programmed cell-death protein 1 (PD-1) inhibitors and 2 programmed cell-death ligand 1 (PD-L1) inhibitors in patients who have progressed during or after platinum-based therapy. Pembrolizumab, nivolumab, and atezolizumab are PD-1 inhibitors. Durvalumab and avelumab are PD-L1 inhibitors. However, only 2 drugs were approved based on phase III clinical trials—pembrolizumab and atezolizumab, of which only KEYNOTE study performed with pembrolizumab showed overall survival difference. Atezolizumab and pembrolizumab are the Food and Drug Administration–approved checkpoint inhibitors in cisplatin-ineligible patients. Conclusion: This review article summarizes the significance of immunotherapy in treatment of bladder cancer, its side effects, and limitations.