PD-1/PD-L1 Combinations in Advanced Urothelial Cancer: Rationale and Current Clinical Trials

Chemotherapy is no longer the only viable option for patients with locally advanced or metastatic urothelial carcinoma. Immunotherapy, as checkpoint inhibition, has received United States Food and Drug Administration approval in the preceding several years, both in the second-line and first-line for cisplatin-ineligible patients. Those who respond often do so durably; however, response rates in the first line are 23% to 24%, and are lower in the second line. With a focus on urothelial carcinoma, this review discusses the tumor microenvironment and its negative influence on anti-tumor immunity, as well as measures to counteract immune suppression or evasion. The review then describes a range of current clinical trials implementing these measures in the form of programmed death-combination therapy, specifically in advanced bladder and urothelial cancers.