title: Prediction of progression-free survival rates after bevacizumab plus interferon versus interferon alone in patients with metastatic renal cell carcinoma: comparison of a nomogram to the Motzer criteria.
abstract: BACKGROUND
  The combination of bevacizumab plus interferon (BEV+IFN) for treatment of metastatic renal cell carcinoma (mRCC) is associated with improved progression-free survival (PFS) in a phase 3 study.
  
  
  OBJECTIVE
  To develop a novel model for prediction of individual PFS using data from the randomized, controlled phase 3 trial of BEV + IFN or interferon alone. The ability of the Motzer criteria for prediction of PFS was also assessed.
  
  
  METHODS
  Pretreatment parameters of 628 patients were included in the Cox regression model predicting PFS at 6, 12, 18, and 24 mo. BEV+IFN was administered to 337 patients; 291 patients received interferon alone. The developed model and the Motzer criteria were internally validated using Harrell's concordance index and calibrated.
  
  
  CONCLUSIONS
  Median PFS was 10.2 versus 4.6 mo (p < 0.001) for patients receiving BEV + IFN or interferon alone, respectively. The novel model relying on age, Karnofsky performance status, baseline albumin, alkaline phosphatase, and time from primary diagnosis to treatment resulted in the highest discrimination (area under the curve [AUC]: 72.8, 75.0, 72.8, and 70.8% at 6, 12, 18, and 24 mo). The AUC of the Motzer criteria risk groups was 63.7, 61.8, 58.6, and 51.8% for the same time points. Comparison of discriminatory ability between the developed model and the Motzer criteria showed statistically significant differences (all p ≤ 0.02). An external validation of the new model is warranted.
  
  
  CONCLUSIONS
  The developed model identified prognostic factors of PFS in mRCC patients treated with BEV+IFN or interferon alone and quantified individual risk of PFS. Relative to the Motzer criteria, the novel model demonstrated better discriminatory properties. The model may serve clinicians in identifying patients who can benefit the most from BEV+IFN versus interferon alone.
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, QC, Canada.
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Maxine
authors.initials: M
authors.lastname: Sun
authors.forename: Joaquin
authors.initials: J
authors.lastname: Bellmunt
authors.forename: Vesna
authors.initials: V
authors.lastname: Sneller
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007372:Interferons / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D049451:Nomograms; D011379:Prognosis
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D007372:Interferons