title: Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206.
abstract: OBJECTIVE
  Bevacizumab is an antibody that binds vascular endothelial growth factor and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN-alpha) is the historic standard initial treatment for RCC. A prospective, randomized, phase III trial of bevacizumab plus IFN-alpha versus IFN-alpha monotherapy was conducted.
  
  
  METHODS
  Patients with previously untreated, metastatic clear cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN-alpha (9 million units subcutaneously three times weekly) or the same dose and schedule of IFN-alpha monotherapy in a multicenter phase III trial. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate, and safety.
  
  
  RESULTS
  Seven hundred thirty-two patients were enrolled. The median OS time was 18.3 months (95% CI, 16.5 to 22.5 months) for bevacizumab plus IFN-alpha and 17.4 months (95% CI, 14.4 to 20.0 months) for IFN-alpha monotherapy (unstratified log-rank P = .097). Adjusting on stratification factors, the hazard ratio was 0.86 (95% CI, 0.73 to 1.01; stratified log-rank P = .069) favoring bevacizumab plus IFN-alpha. There was significantly more grade 3 to 4 hypertension (HTN), anorexia, fatigue, and proteinuria for bevacizumab plus IFN-alpha. Patients who developed HTN on bevacizumab plus IFN-alpha had a significantly improved PFS and OS versus patients without HTN.
  
  
  CONCLUSIONS
  OS favored the bevacizumab plus IFN-alpha arm but did not meet the predefined criteria for significance. HTN may be a biomarker of outcome with bevacizumab plus IFN-alpha.
authors.affiliation: Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Ave/Desk R35, Cleveland, OH 44195, USA. rinib2@ccf.org
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Rosenberg
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Vaena
authors.forename: Laura
authors.initials: L
authors.lastname: Archer
authors.forename: James N
authors.initials: JN
authors.lastname: Atkins
authors.forename: Joel
authors.initials: J
authors.lastname: Picus
authors.forename: Piotr
authors.initials: P
authors.lastname: Czaykowski
authors.forename: Janice
authors.initials: J
authors.lastname: Dutcher
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002170:Canada; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D016898:Interferon-alpha / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016898:Interferon-alpha; D000068258:Bevacizumab