Sequencing Systemic Therapies for Metastatic Kidney Cancer

Abstract: Defining the appropriate sequencing of therapies for metastatic renal cell carcinoma (mRCC) has become increasingly complex in recent years given the approval of multiple targeted therapies. These targeted therapies fall into 2 broad mechanistic categories: (1) inhibitors of the mammalian target of rapamycin (mTOR), and (2) vascular endothelial growth factor (VEGF)-directed agents. In the current manuscript, data from relevant trials are reviewed to provide a context in which to use these agents across the first- and second-line setting. Strategies to incorporate promising agents currently in late stage development for mRCC are also described.

Opinion statement: Currently, there is no consensus as to the optimal sequence of therapies for patients with metastatic renal cell carcinoma (mRCC). While interleukin-2 (IL-2) and temsirolimus are potential considerations for selected patients in the first-line setting, the majority of patients in this setting are likely candidates for vascular endothelial growth factor (VEGF)-directed therapies. Specifically, these therapies include sunitinib, pazopanib, and bevacizumab/interferon-α. Using the comparative data discussed herein, the relative merits of each should be discussed. In the second-line setting (following VEGF-directed therapy), axitinib, and everolimus are supported by phase III data. There is no data directly comparing the 2 agents—however, studies reviewed in the current manuscript (comparing VEGF- and mammalian target of rapamycin [mTOR]-directed approaches in the second-line setting) can potentially be used to inform clinical decision making.