title: What is the optimal therapy for patients with metastatic renal cell carcinoma who progress on an initial VEGFr-TKI?
abstract: Sequential treatment with targeted therapies is the current standard of care for patients with metastatic renal cell carcinoma (mRCC). Most patients are initially treated with a first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI), but will eventually develop resistance and subsequent disease progression. Patients with mRCC whose disease progresses during initial VEGFr-TKI therapy may continue treatment with a different VEGFr-TKI or they may switch to treatment with a mammalian target of rapamycin (mTOR) inhibitor which has a different mechanism of action. Based on positive results of the phase III RECORD-1 trial, clinical guidelines in the United States and Europe recommend use of everolimus, an mTOR inhibitor, in patients with VEGFr-TKI-refractory mRCC. Positive results of the phase III AXIS trial led to recent approval in the United States of the VEGFr-TKI axitinib for use in patients with mRCC who failed one previous therapy. VEGFr-TKIs and mTOR inhibitors have distinct clinical effects with differing safety profiles, but to date, no head-to-head comparisons in the post-VEGFr-TKI second-line setting are available. This review discusses multiple factors that should be considered when selecting a second-line therapy for patients with VEGFr-TKI-refractory mRCC, including evidence-based guidelines, efficacy, safety, patient profile, and clinician familiarity with available agents.
authors: Centro Integral Oncológico Clara Campal and START Madrid, Madrid, Spain. emiliano.calvo@start.stoh.com
authors: Emiliano
authors: E
authors: Calvo
authors: Alain
authors: A
authors: Ravaud
authors: Joaquim
authors: J
authors: Bellmunt
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors
chemical_list: D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D058570:TOR Serine-Threonine Kinases