First-line systemic treatment options for advanced renal cell carcinoma

The treatment of advanced clear cell renal cell carcinoma (ccRCC) has undergone significant changes over the last two decades, particularly with the development of antiangiogenic therapies, in particular vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). The first-line therapeutic paradigm is dominated by combination therapies of ICI/ICI or TKI/ICI, although high-dose interleukin (IL)-2 or individual TKIs are still used in limited circumstances. This chapter provides a historical overview with a focus on currently FDA approved ICI combinations: ipilimumab/nivolumab, axitinib/pembrolizumab, axitinib/avelumab, cabozantinib/nivolumab, and lenvatinib/pembrolizumab. Challenges and approaches to therapeutic choices are also explored.