Immunotherapy for Urothelial Carcinoma: Current Evidence and Future Directions.

PURPOSE OF REVIEW

Until recently, effective treatment options for patients with advanced urothelial carcinoma were limited to platinum-based chemotherapy. In the post-platinum setting and for patients ineligible for cisplatin, minimally effective second-line chemotherapy was used and outcomes were poor. The approval of immune checkpoint inhibitors has significantly changed the treatment landscape of urothelial carcinoma. Here, we review current data demonstrating their efficacy in advanced disease and ongoing trials investigating novel combination strategies.

RECENT FINDINGS

Since May 2016, five agents targeting the programmed cell death 1 (PD-1) pathways have been approved for use after progression on platinum-based chemotherapy. Further, atezolizumab and pembrolizumab are approved for use in cisplatin-ineligible patients with high programmed death-ligand 1 (PD-L1) expression. Preliminary studies have shown their safety and efficacy as neoadjuvant therapy in muscle-invasive bladder cancer. Several ongoing trials are investigating these agents in combination with radiation therapy, platinum-based chemotherapy, other immune checkpoint inhibitors, and targeted agents. Immune checkpoint inhibitors have demonstrated durable efficacy in patients with advanced urothelial carcinoma as first- and second-line therapy. Ongoing studies will help define the optimal sequence, combination strategies, and predictive biomarkers of response.