title: Efficacy of everolimus in second- and third-line therapy for metastatic renal cell carcinoma: a registry-based analysis.
abstract: OBJECTIVE
  The aim of the present study was to describe the efficacy and safety of everolimus in the treatment of metastatic renal cell carcinoma (mRCC) after administration of 1 vs. 2 prior tyrosine kinase inhibitors (TKIs).
  
  
  METHODS
  A national renal information system database was used as the data source for the retrospective study. There were 483 patients who received everolimus as the second (n = 350) or the third (n = 112) targeted agent following TKIs.
  
  
  RESULTS
  Median progression-free survival (PFS) from the start of everolimus in the second or the third line of targeted therapy was 6.1 months for both subgroups (P = 0.863). Median total PFS from the start of the first targeted agent to progression on the third targeted agent for patients receiving 3 lines of therapy with TKI-TKI-everolimus (n = 112) and TKI-everolimus-TKI (n = 27) sequences was 28.3 months vs. 31.3 months, respectively (P = 0.16), and there was no significant difference in overall survival. PFS on everolimus was associated with PFS on previous TKIs in patients receiving 1 but not 2 previous TKIs. Only 13% of 352 patients starting targeted therapy for mRCC in 2010 had received 3 sequential targeted agents by the data cutoff in March 2013.
  
  
  CONCLUSIONS
  PFS on everolimus correlated with PFS on TKIs in patients pretreated with 1 but not 2 TKIs. Everolimus can be deferred to the third line without loss of efficacy or increased toxicity. However, only a minority of patients with mRCC starting targeted treatment can be expected to receive third-line therapy.
authors.affiliation: Department of Oncology, Thomayer Hospital and Charles University First Faculty of Medicine, Prague, Czech Republic. Electronic address: tomas.buchler@ftn.cz.
authors.forename: Tomas
authors.initials: T
authors.lastname: Buchler
authors.affiliation: Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic.
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Bortlicek
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: Alexandr
authors.initials: A
authors.lastname: Poprach
authors.affiliation: Department of Oncology, Motol University Hospital and Charles University Second Faculty of Medicine, Prague, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Kubackova
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: Igor
authors.initials: I
authors.lastname: Kiss
authors.affiliation: Department of Oncology, General University Hospital and Charles University First Faculty of Medicine, Prague, Czech Republic.
authors.forename: Milada
authors.initials: M
authors.lastname: Zemanova
authors.affiliation: Department of Oncology, University Hospital, Pilsen, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Fiala
authors.affiliation: Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Dusek
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: Rostislav
authors.initials: R
authors.lastname: Vyzula
authors.affiliation: Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic.
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Melichar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D016208:Databases, Factual; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004358:Drug Therapy / Q000379:methods; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012042:Registries; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D000068338:Everolimus; D011505:Protein-Tyrosine Kinases; D020123:Sirolimus
keywords: Everolimus; Renal cell carcinoma; Therapy; Tyrosine kinase inhibitors; mTOR