Programmed cell death-1 pathway inhibitors in genitourinary malignancies: specific side-effects and their management

Immune checkpoint inhibitors such as those that target the programmed cell death (PD)-1 pathway harness the host immune system to elicit an antitumor response. Their remarkable clinical benefit has led to regulatory approvals in several malignancies including the genitourinary cancers, renal cell carcinoma, and urothelial carcinoma. This review will focus on the management of the toxicities encountered with these agents.

Although generally well tolerated, a small proportion of patients (10-20%) treated with PD-1 directed agents as monotherapy can develop severe autoimmune manifestations, also known as, immune-related adverse events. These include but are not limited to rashes, pneumonitis, endocrinopathy, colitis, and immune-mediated hepatic dysfunction. Combining these agents with the anti-CTLA-4 antibody ipilimumab can be associated with a higher incidence of these toxicities. Early initiation of immunosuppression with corticosteroids and other agents when needed can help mitigate these toxicities and to date has not been shown to compromise their clinical benefit.

The development of immune checkpoint inhibitors represents significant advances in anticancer therapy but their efficacy may come at the cost of autoimmune toxicities secondary to their induction of the immune system. Early recognition of these effects and aggressive upfront management is essential to safely administer these agents in routine clinical practice.