title: Survival prediction in everolimus-treated patients with metastatic renal cell carcinoma incorporating tumor burden response in the RECORD-1 trial.
abstract: BACKGROUND
  The phase 3 RECORD-1 study demonstrated clinical benefit of everolimus over placebo (median progression-free survival: 4.9 mo compared with 1.9 mo, p<0.001) in treatment-resistant patients with metastatic renal cell carcinoma (mRCC). However, the Response Evaluation Criteria in Solid Tumors (RECIST) objective response rate was low.
  
  
  OBJECTIVE
  To explore the potential role of tumor burden response to everolimus in predicting patient survival.
  
  
  METHODS
  RECORD-1 patients with at least two tumor assessments (baseline and weeks 2-14) were included (n=246).
  
  
  METHODS
  A multivariate Cox proportional hazard model was used to assess the impact of various prognostic factors on overall survival (OS). Components of RECIST progression were explored using univariate Cox regression.
  
  
  CONCLUSIONS
  The baseline sum of longest tumor diameters (SLD) and progression at weeks 2-14 were prognostic factors of OS by multivariate analysis. Univariate analysis at weeks 2-14 demonstrated that growth of nontarget lesions and appearance of new lesions were predictive of OS (p<0.001). This retrospective analysis used data from one arm of one trial; patients in the placebo arm were excluded because of confounding effects when they crossed over to everolimus.
  
  
  CONCLUSIONS
  This analysis identified baseline SLD as a predictive factor of OS, and the appearance of a new lesion or progression of a nontarget lesion at first assessment after baseline also affects OS in patients with mRCC treated with everolimus.
authors.affiliation: Novartis Institutes for Biochemical Research, Cambridge, MA, USA. Electronic address: andrew.stein@novartis.com.
authors.forename: Andrew
authors.initials: A
authors.lastname: Stein
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.forename: Dennis
authors.initials: D
authors.lastname: Kim
authors.forename: Sotirios G
authors.initials: SG
authors.lastname: Stergiopoulos
authors.forename: William
authors.initials: W
authors.lastname: Mietlowski
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology / Q000556:secondary; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis; D011379:Prognosis; D012189:Retrospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015996:Survival Rate; D047368:Tumor Burden / Q000187:drug effects*
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus