First-Line Systemic Therapy for Metastatic Clear-Cell Renal Cell Carcinoma: Critical Appraisal of Emerging Options

Until recently, a dichotomy existed in the front-line approach of metastatic clear-cell renal cell carcinoma (mRCC). Specifically, patients received either targeted therapy or immunotherapy. Targeted therapy entailed use of agents blocking signaling through the vascular endothelial growth factor (VEGF) receptor, such as cabozantinib, sunitinib, or pazopanib. Immunotherapy entailed dual therapy with nivolumab and ipilimumab, both checkpoint inhibitors for intermediate/poor International Metastatic RCC Database Consortium (IMDC)-risk disease patients. Within the past year, two datasets have emerged that led to recent approvals of combined therapy with VEGF and checkpoint inhibitors. These regimens (axitinib with either avelumab or pembolizumab) are among several that have been or will be evaluated for patients with newly diagnosed mRCC. We aim to facilitate treatment decisions through this comprehensive and contextualized overview of recent datasets in this therapeutic space.