Checkpoint inhibitors and other novel immunotherapies for advanced renal cell carcinoma.

The management of advanced renal cell carcinoma (RCC) has dramatically changed over the past decade. Therapies that target the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways have considerably expanded treatment options; however, most patients with advanced RCC still have limited overall survival. Increased understanding of the mechanisms of T cell-antigen recognition and function has led to the development of novel immunotherapies to treat cancer, chief among them inhibitors of checkpoint receptors - molecules whose function is to restrain the host immune response. In 2015, the FDA approved the first checkpoint inhibitor nivolumab for patients with advanced RCC following treatment with antiangiogenic therapy based on improved overall survival compared with the standard of care. Ongoing phase III trials are comparing checkpoint-inhibitor-based combination regimens with antiangiogenesis agents in the first-line setting. The field is evolving rapidly, with many clinical trials already testing several checkpoint inhibitors alone, in combination, or with other targeted therapies. In addition, different novel immune therapies are being investigated including vaccines, T-cell agonists, and chimeric antigen receptor T cells. Determining which patients will benefit from these therapies and which combination approaches will result in better response will be important as this field evolves.