title: Efficacy of everolimus in patients with advanced renal cell carcinoma refractory or intolerant to VEGFR-TKIs and safety compared with prior VEGFR-TKI treatment.
abstract: OBJECTIVE
  Everolimus is positioned as second-line treatment for metastatic renal cell carcinoma resistant to vascular endothelial growth factor receptor-tyrosine kinase inhibitors. We investigated retrospectively the efficacy and safety of everolimus in Japanese patients with advanced renal cell carcinoma in the clinical setting.
  
  
  METHODS
  Nineteen patients who discontinued treatment with vascular endothelial growth factor receptor-tyrosine kinase inhibitors because of disease progression or adverse events were administered everolimus. We evaluated progression-free survival, overall survival and tumor response rate of everolimus treatment. We also compared laboratory abnormalities and adverse events of everolimus treatment with those of prior vascular endothelial growth factor receptor-tyrosine kinase inhibitors therapy.
  
  
  RESULTS
  In all patients, median progression-free survival was 8.4 months and median overall survival was not reached at 25 months. The best objective response was complete response in 1 patient and stable disease in 15 patients. Eleven patients (58%) were intolerant and 8 (42%) were refractory to prior vascular endothelial growth factor receptor-tyrosine kinase inhibitors treatment. Median overall survival was significantly longer (P < 0.01) in vascular endothelial growth factor receptor-tyrosine kinase inhibitor-intolerant (>25 months) than in vascular endothelial growth factor receptor-tyrosine kinase inhibitor-refractory subjects (4.3 months), and median progression-free survival tended to be better (P= 0.06) in vascular endothelial growth factor receptor-tyrosine kinase inhibitor-intolerant (10.0 months) than in vascular endothelial growth factor receptor-tyrosine kinase inhibitor-refractory subjects (2.5 months). Two patients discontinued everolimus treatment because of adverse events.
  
  
  CONCLUSIONS
  In this study, the overall survival and progression-free survival were better in vascular endothelial growth factor receptor-tyrosine kinase inhibitor-intolerant than in vascular endothelial growth factor receptor-tyrosine kinase inhibitor-refractory subjects. The adverse event profiles of everolimus and vascular endothelial growth factor receptor-tyrosine kinase inhibitors were different. Patients intolerant to vascular endothelial growth factor receptor-tyrosine kinase inhibitors may tolerate everolimus well and have greater survival benefit from switching to everolimus than those refractory to vascular endothelial growth factor receptor-tyrosine kinase inhibitors.
authors.affiliation: *Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka-shi, Iwate 020-8505, Japan. nsd41937@nifty.com.
authors.forename: Renpei
authors.initials: R
authors.lastname: Kato
authors.forename: Wataru
authors.initials: W
authors.lastname: Obara
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Matsuura
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kato
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fujioka
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018450:Disease Progression; D018572:Disease-Free Survival; D000068338:Everolimus; D005260:Female; D006801:Humans; D007564:Japan; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D012189:Retrospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068338:Everolimus; D011505:Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D020123:Sirolimus
keywords: adverse event; everolimus; renal cell carcinoma; survival outcome; vascular endothelial growth factor receptor-tyrosine kinase inhibitor