title: Clinical outcome in metastatic renal cell carcinoma patients after failure of initial vascular endothelial growth factor-targeted therapy.
abstract: OBJECTIVE
  To characterize and evaluate the efficacy of second-line therapy in patients who had progressed on initial anti-vascular endothelial growth factor (VEGF) therapy.
  
  
  METHODS
  Between 2005 and 2007, patients with mRCC who received second-line therapy after 1st-line VEGF-targeted therapy were identified across 7 cancer centers.
  
  
  RESULTS
  A total of 645 mRCC patients received first-line VEGF-targeted therapy, of which 216 patients received second-line VEGF-targeted therapy (sunitinib, n = 93; sorafenib, n = 80; bevacizumab, n = 11; axitinib, n = 8) or mammalian target of rapamycin (mTOR)-inhibiting agents (temsirolimus, n = 21; everolimus, n = 3). On multivariate analysis, a higher baseline Karnofsky performance status score before first-line therapy predicted which patients were more likely to receive second-line therapy (P <.0001). The median time to treatment failure of second-line therapy was 4.9 months for anti-VEGF therapy and 2.5 months for mTOR inhibitors (P = .014) (HR: 0.52, CI: 0.29-0.91 and HR: 0.495, CI: 0.27-0.9 after adjusting for Memorial Sloan-Kettering Cancer Center prognostic factors and histology, respectively). Overall survival from start of second-line therapy was not significantly different (14.2 vs 10.6 months respectively; P = .38).
  
  
  CONCLUSIONS
  Baseline Karnofsky performance status is an independent predictor of receiving second-line targeted therapy. Patients who receive a second-line anti-VEGF drug appear to have a similar overall survival to those who receive a second-line anti-mTOR drug.
authors.affiliation: Department of Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Vickers
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: Miranda
authors.initials: M
authors.lastname: Rogers
authors.forename: Andrew
authors.initials: A
authors.lastname: Percy
authors.forename: Daygen
authors.initials: D
authors.lastname: Finch
authors.forename: Ivan
authors.initials: I
authors.lastname: Zama
authors.forename: Tina
authors.initials: T
authors.lastname: Cheng
authors.forename: Scott
authors.initials: S
authors.lastname: North
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.forename: Christian
authors.initials: C
authors.lastname: Kollmannsberger
authors.forename: David F
authors.initials: DF
authors.lastname: McDermott
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: Daniel Y
authors.initials: DY
authors.lastname: Heng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A