Treatment sequencing strategies in metastatic renal cell carcinoma: A critical interpretation of available data

Abstract

Therapeutic sequencing strategies for metastatic renal cell carcinoma have evolved significantly over time. For about 10 years, vascular endothelial growth factor receptor-targeted therapies and mammalian target of rapamycin inhibitors have been the standard of care. About 5 years ago an immunocheckpoint inhibitor, nivolumab, has opened new therapeutic perspectives. Recent clinical studies have confirmed the biological rationale of combining two immunocheckpoint inhibitors or vascular endothelial growth factor-targeted therapies plus immunocheckpoint inhibitors, demonstrating an improvement in clinical outcomes. We are still unable to recognize immunocheckpoint inhibitors responder patients from vascular endothelial growth factor-targeted therapies responder patients and, therefore, to quantify in a certain patient the benefits/harms ratio of upfront combination over sequence therapy in a certain patient. However, the metastatic renal cell carcinoma records of high-volume cancer centers could reveal the effectiveness and tolerability of combined treatments and indicate the potentially predictive factors and the management strategies in the real-world population.