MTOR and renal cell carcinoma: In TIVO-1, a randomized, open-label, phase 3 trial, Tivozanib showed a significative PFS advantage compared with Sorafenib as initial VEGF-targeted therapy [50] and its use was approved in the European Union as a first-line treatment of advanced RCC and for patients who are VEGFR and mTOR pathway inhibitor-naïve following disease progression after one prior treatment with cytokine therapy for advanced RCC [51].