New approaches to first-line treatment of advanced renal cell carcinoma

Abstract

The treatment of patients with renal cell carcinoma (RCC) is evolving rapidly, with promising new regimens being developed and approved for patients with advanced disease, particularly the combination of tyrosine kinase inhibitors with immune checkpoint inhibitors. Within the last 6 months, favorable first-line setting results for patients with clear cell RCC have been reported for the combination of cabozantinib plus nivolumab in the phase III CheckMate 9ER study, leading to its regulatory approval, and lenvatinib plus pembrolizumab in the phase III CLEAR study. Additional systemic first-line treatments for clear cell RCC include axitinib plus pembrolizumab, pazopanib, and sunitinib for favorable-risk patients and ipilimumab plus nivolumab, axitinib plus pembrolizumab, axitinib plus avelumab, and cabozantinib for intermediate- or poor-risk patients. In this review of novel approaches for first-line treatment of advanced RCC, we present an overview of current treatment strategies, the basis behind emerging treatment approaches, a summary of key results from the pivotal studies using tyrosine kinase inhibitor and immune checkpoint inhibitor combination therapy, novel treatments and strategies under development, and efforts for identifying biomarkers to guide treatment decisions.

Keywords: anti-VEGF; first line; immune checkpoints inhibitors; renal cell carcinoma; tyrosine kinase inhibitors.

Figure 1.

Impact on the tumor microenvironment of VEGF-targeted monotherapy (a) and VEGF-targeted therapy combined with ICI (b). CR, complete response; DC, dendritic cell; DCR, disease control rate; ICI, immune checkpoint inhibitor; MDSC, myeloid-derived suppressor cells; ORR, objective response rate; Treg, T-regulatory cells; VEGF, vascular endothelial growth factor.