The immunotherapy revolution in kidney cancer treatment: Scientific rationale and first-generation results

The recent discovery of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, including the treatment for renal cell carcinoma (RCC). Following the eras of cytokines and molecularly targeted therapies including vascular endothelial growth factor-directed agents and mammalian target of rapamycin (mTOR) inhibitors, ICIs have become the latest addition to the RCC armamentarium. To understand the scientific rationale behind this revolution in RCC treatment, we have reviewed the fundamental discoveries underlying the transition from old (cytokines) to new (ICIs) immunotherapies. We summarize the pivotal trials (CheckMate 025, CheckMate 214, KEYNOTE-426, JAVELIN Renal 101, IMmotion151) of checkpoint inhibitors for clear cell RCC in various treatment settings. With the availability of many different combination therapies and many more currently under investigation, clear cell RCC treatment is becoming more complex. Patient preferences, disease volumes, and adverse event profiles are essential in determining which option is the best for an individual patient. In the future, biomarkers currently under development could guide these treatment decisions.