Treatment selection for patients with metastatic renal cell carcinoma: identification of features favoring upfront IL-2-based immunotherapy

The availability of approved agents with distinct mechanisms of action (immunotherapy, vascular endothelial growth factor pathway, and mTOR inhibitors) has complicated treatment decisions for patients with advanced kidney cancer. High-dose IL-2 therapy is the only treatment that can produce durable complete responses; however, it has significant side effects and the vast majority of patients do not benefit. Thus, identifying the optimal patients to receive first-line IL-2 therapy is a priority. Past studies have identified some clinical features that might be associated with benefit from IL-2-based immunotherapy. Subsequent investigations of tumors from patients treated with IL-2 suggested that response was unlikely in patients with tumors with papillary features or low carbonic anhydrase IX (CAIX) expression. A model combining histologic features and CAIX expression separated patients into two groups of roughly equal size, with 96% of long-term responding patients being in the favorable prognostic group. This model is currently undergoing prospective validation. More recent studies involving gene expression profiling and array CGH have begun to identify additional features that might predict response to IL-2 therapy. Taken together, these data offer the possibility to limit the use of this toxic therapy to those most likely to benefit.