Targeted therapies and immunotherapy in bladder cancer

Abstract

Cisplatin-based combination chemotherapy is still the standard first-line regimen for the treatment of metastatic urothelial carcinoma. Although the efficacy of targeted therapies was shown in most of the solid tumors, no targeted agent was approved until now in bladder cancer. Due to the preliminary phase II results of gemcitabine, cisplatin plus bevacizumab demonstrated promising objective response rate, overall survival, and progression-free survival in the first-line treatment of metastatic bladder cancer; a phase III is ongoing. The major advances in understanding the genetic background of urothelial tumors open up a new therapeutic area. Although the application of checkpoint inhibitors in bladder cancer is in its starting phase, the available results suggest that patients with metastatic disease and positive programmed death-ligand-1 (PD-L1) expression will derive the highest clinical benefit. Atezolizumab, an anti-PD-L1 monoclonal antibody, was approved by the Food and Drug Administration for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease progressed after previous platinum-based chemotherapy. Both pembrolizumab and nivolumab, anti-PD-1 monoclonal antibodies, demonstrated antitumor activity with tolerable safety in patients with recurrent or metastatic urothelial cancer patients. Combination therapies to treat bladder cancer, involving cytotoxic chemotherapy, antiangiogenic agents, and immune checkpoint inhibitors, are currently ongoing.