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For the past decade, the standard treatment for patients with metastatic renal cell carcinoma has been the sequential use of single agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways. Efforts to combine VEGF- and mTOR-targeted agents have been for the most part disappointing, with limited evidence of increased activity at the expense of greater toxicity. However, preclinical work has shown that combining the multitarget tyrosine kinase inhibitor of VEGFR lenvatinib and the mTOR inhibitor everolimus reduced renal cell tumor volume significantly more than did either lenvatinib or everolimus alone.
To further test the efficacy of this combination therapy, international investigators …