Abstract
Simple SummaryIn this review, we examined relevant clinical trial results with immune checkpoint inhibitors in patients with metastatic urothelial cancer. We also focused on the potential of immunotherapy in the adjuvant and neoadjuvant setting or as part of drug combinations. Finally, we briefly review the current landscape of biomarkers of response to immune checkpoint inhibitors, such as programmed death-ligand 1 (PD-L1) expression, tumor mutation burden, molecular subtypes of bladder cancer, and immune-gene expression profiling.A number of immune checkpoint inhibitors (ICIs) have been approved as first-line therapy in case of cisplatin-ineligible patients or as second-line therapy for patients with metastatic urothelial carcinoma (mUC) of the bladder. About 30% of patients with mUC will respond to ICIs immunotherapy. Programmed death-ligand 1 (PD-L1) expression detected by immunohistochemistry seems to predict response to immune checkpoint inhibitors in patients with mUC as supported by the objective response rate (ORR) and overall survival (OS) associated with the response observed in most clinical trials. Pembrolizumab, an anti-PD-1 antibody, demonstrated better OS respective to chemotherapy in a randomized phase 3 study for second-line treatment of mUC. Nivolumab, a PD-1 antibody, also demonstrated an OS benefit when compared to controls. Atezolizumab, Durvalumab, and Avelumab antibodies targeting PD-L1 have also received approval as second-line treatments for mUC with durable response for more than 1 year in selected patients. Atezolizumab and Pembrolizumab also received approval for first-line treatment of patients that are ineligible for cisplatin. A focus on the utility of ICIs in the adjuvant or neoadjuvant setting, or as combination with chemotherapy, is the basis of some ongoing trials. The identification of a clinically useful biomarker, single or in association, to determine the optimal ICIs treatment for patients with mUC is very much needed as emphasized by the current literature. In this review, we examined relevant clinical trial results with ICIs in patients with mUC alone or as part of drug combinations; emphasis is also placed on the adjuvant and neoadjuvant setting. The current landscape of selected biomarkers of response to ICIs including anti-PD-L1 immunohistochemistry is also briefly reviewed.
Highlights
A major paradigm shift in bladder cancer medicine was related to the FDA approval and launch of Avelumab, Pembrolizumab, Durvalumab, Atezolizumab, and Nivolumab to treat patients with metastatic urothelial carcinoma (mUC) being previously treated with chemotherapy
The use of drug combinations of Anti-Programmed death-ligand 1 (PD-L1)/progressive disease (PD)-1 and Anti-CTL4 seems to be important in metastatic bladder cancer and is part of several ongoing clinical trials
High disease burden is defined as a high number of metastatic sites involvement and specific patterns of disease progression, which are clinically accessible parameters that are predictive of first-line immune checkpoint inhibitors (ICIs) based immunotherapy failure
Summary
We report on the current association between PD-L1 expression, treatment with immune checkpoint inhibitors, and outcomes in patients with mUC of the bladder. To cohort 2, ORR in cohort 1 appeared to be independent of PD-L1 status (ORR of 28% vs 21% for high and low PD-L1 immune cells expression, respectively). Median OS was independent of PD-L1 status (12.3 vs 19.1 months for high and low PD-L1 immune cells expression, respectively). In both cohorts, the most common adverse events (AEs) were diarrhea, fatigue, and/or pruritus with rare examples of autoimmune phenomena commonly associated with PD-L1 inhibitors including pneumonia, transaminitis, and hypothyroidism
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
