title: Sequential therapy in metastatic clear cell renal carcinoma: TKI-TKI vs TKI-mTOR.
abstract: With seven targeted agents, directed against the VEGF/VEGF receptor (VEGFR) axis or the mTOR pathway, approved for the treatment of metastatic renal cell carcinoma and more active agents in advanced phase of clinical testing, questions have arisen with regard to their optimal use, either in combination or in sequence. One of the most compelling (and debated) issues is whether continued VEGF/VEGFR inhibition with agents hitting the same targets (TKI-TKI) affords better results than switching mechanisms of action by alternating VEGFR and mTOR inhibition (TKI-mTOR). In this article, the authors review the (little) available evidence coming from randomized Phase III clinical trials and try to fill in the (many) remaining gaps using evidence from small-size, single-arm Phase II studies and retrospective series, as well as reviewing preclinical evidence supporting either strategy.
authors.affiliation: Division of Medical Oncology A, Regina Elena National Cancer Institute,Via Elio Chianesi 53, 00144, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Felici
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.forename: Michele
authors.initials: M
authors.lastname: Milella
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D058990:Molecular Targeted Therapy; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases