Recent Developments in the Management of Renal Cell Cancer

The management of renal cell carcinoma (RCC) has seen significant advancements in recent years with the introduction of novel therapeutic agents and combination regimens. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape, particularly for advanced and metastatic RCC, where ICI-based combinations have shown substantial improvements in survival outcomes. Dual immunotherapy combinations, such as nivolumab plus ipilimumab, and ICI-vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) combinations, including pembrolizumab with axitinib, nivolumab with cabozantinib, and pembrolizumab with lenvatinib, have demonstrated overall survival (OS) benefits in first-line treatment, redefining the standard of care for advanced RCC. Adjuvant pembrolizumab is also approved for resected high-risk RCC and is the only adjuvant therapy that prolongs the OS in RCC. Additionally, the development of belzutifan, a hypoxia-inducible factor-2 alpha inhibitor, offers a new treatment option for patients whose disease progresses after ICI and VEGF TKI therapies. Recent results from CONTACT-3 and TiNiVo-2 confirm that ICI rechallenge should be generally discouraged. This review provides a detailed overview of the current evidence supporting immune-based combinations and novel agents such as belzutifan, as well as insights into treatment sequencing strategies for RCC.