title: Therapy of mRCC beyond mTOR-inhibition in clinical practice: results of a retrospective analysis.
abstract: OBJECTIVE
  Renal cell carcinoma (RCC) is the most common renal tumor and accounts for nearly 3 % of adult cancers. In the recent years, seven new targeted agents have been approved changing the treatment in metastatic RCC dramatically. So far, however, it remains unclear which sequence is best for those patients. This study analyzed retrospectively the outcome of patients treated with everolimus after failure of a vascular endothelial growth factor receptor-directed therapy and which therapies were used after everolimus.
  
  
  METHODS
  In a retrospective analysis, patients receiving everolimus after failure of first-line VEGFR-directed therapy have been analyzed in regard to response, duration of treatment and subsequent therapies. In total, the data of 81 patients have been analyzed.
  
  
  RESULTS
  The most observed first-line therapy was sunitinib followed by sorafenib. Thirty-two patients received everolimus as second-line therapy, and 49 as third-line therapy. The median duration of treatment with everolimus was 4.5 months. Seventy-seven of eighty-one patients (95 %) received a further therapy after discontinuation of everolimus. The agents administered beyond were sunitinib (28.6 %), sorafenib (28.6 %) and 42.8 % received other therapies. Twenty-seven patients received an additional sequence of therapy (fourth to fifth line). Fifty-eight percentage of patients have still been alive at time of analysis.
  
  
  CONCLUSIONS
  The duration of everolimus therapy beyond failure of anti-VEGF-directed therapy and the reported time to progression was in the range of the RECORD-1 trial in daily practice as well. After failure of everolimus, reexposure to tyrosine kinase inhibitors is a common clinical practice and demonstrates a clinical benefit of therapies beyond everolimus.
authors.affiliation: Department of Internal Medicine II, Hematology and Oncology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany, luise.maute@kgu.de.
authors.forename: Luise
authors.initials: L
authors.lastname: Maute
authors.forename: Viktor
authors.initials: V
authors.lastname: Grünwald
authors.forename: Steffen
authors.initials: S
authors.lastname: Weikert
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kube
authors.forename: Thomas
authors.initials: T
authors.lastname: Gauler
authors.forename: Christoph
authors.initials: C
authors.lastname: Kahl
authors.forename: Iris
authors.initials: I
authors.lastname: Burkholder
authors.forename: Lothar
authors.initials: L
authors.lastname: Bergmann
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D000068338:Everolimus; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077157:Sorafenib; D000077210:Sunitinib; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D007211:Indoles; D010671:Phenylurea Compounds; D011758:Pyrroles; D009536:Niacinamide; D000068338:Everolimus; D000077157:Sorafenib; C546842:MTOR protein, human; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases; D000077210:Sunitinib; D020123:Sirolimus