Immunotherapy in urothelial cancer: current status and future directions

IntroductionSince 2016, the progressive use of immune checkpoint inhibitors (ICIs) starting from second-line treatment has led to an improvement in overall survival in locally advanced and metastatic urothelial cancer (UC). Clinical trials are underway testing the role of ICIs since the first stages of the disease, alone or in combination with standard therapies.Areas coveredThis review summarizes the current updated evidence regarding the role of ICIs in the different stages of UC, the ongoing clinical trials exploring the potential benefit of immunotherapy alone or in combination with standard-of-care therapies, as well as the promising association of ICIs with antibody-drug conjugates (ADCs).Expert opinionIn the first-line setting, ICIs alone in platinum-unfit patients have shown unconvincing results; the ongoing EV-302 trial will probably suggest enfortumab vedotin plus pembrolizumab as a new effective option. The optimal duration of maintenance immunotherapy is still to be determined, finding a balance with the risk-benefit profile. The clinical benefit of ICIs as second-line treatment is limited to a subset of patients that cannot be definitively established yet. In the next 5 years, a lot of new ADCs will likely emerge for the treatment of UC.

Automated summary

This review summarizes the current evidence and ongoing clinical trials of immune checkpoint inhibitors (ICIs) in urothelial cancer (UC), discussing their role in different stages of the disease and potential benefits in combination with standard therapies. The use of ICIs as first-line treatment in platinum-unfit patients is still uncertain, but a new effective option may emerge from the ongoing EV-302 trial. The optimal duration of maintenance immunotherapy and the definitive patient subset for second-line treatment with ICIs are still under investigation. A promising association of ICIs with antibody-drug conjugates (ADCs) is also highlighted.