Update of systemic immunotherapy for advanced urothelial carcinoma

Until recently, therapeutic options for metastatic urothelial carcinoma (UC) were limited to cytotoxic chemotherapy. Cisplatin-based combination chemotherapy has proven benefit in the perioperative settings for muscle-invasive disease and for metastatic disease. A large proportion of patients is cisplatin-ineligible and limited to less effective chemotherapeutic options. However, treatment options have recently expanded with the development of systemic immunotherapy with checkpoint inhibitors (CPIs).Herein we review the clinical trial data supporting the use of CPIs in UC. We also describe ongoing clinical trials that are exploring CPIs in novel combinations and in a variety of disease settings.

A comprehensive literature review was performed using Medline/Pubmed and clinical trials.

Based on results of the IMvigor 210 clinical trial, the anti-programmed death-ligand1 antibody atezolizumab gained regulatory approval in May 2016 for use in locally advanced and metastatic UC in patients with progression of disease despite prior platinum-based chemotherapy. Since that time, additional CPIs (avelumab, durvalumab, nivolumab, and pembrolizumab) have gained regulatory approval in the postplatinum setting. The approval of pembrolizumab was supported by KEYNOTE-045, the first reported randomized, phase III trial of a CPI in UC. Atezolizumab and pembrolizumab are also approved for first-line therapy for cisplatin-ineligible patients with locally advanced or metastatic disease. The rapid expansion of therapeutic options in UC has shifted the treatment paradigm.