Sunitinib versus interferon alfa in metastatic renal-cell carcinoma

N Engl J Med. 2007 Jan 11;356(2):115-24. doi: 10.1056/NEJMoa065044.

Abstract

Background: Since sunitinib malate has shown activity in two uncontrolled studies in patients with metastatic renal-cell carcinoma, a comparison of the drug with interferon alfa in a phase 3 trial is warranted.

Methods: We enrolled 750 patients with previously untreated, metastatic renal-cell carcinoma in a multicenter, randomized, phase 3 trial to receive either repeated 6-week cycles of sunitinib (at a dose of 50 mg given orally once daily for 4 weeks, followed by 2 weeks without treatment) or interferon alfa (at a dose of 9 MU given subcutaneously three times weekly). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, patient-reported outcomes, and safety.

Results: The median progression-free survival was significantly longer in the sunitinib group (11 months) than in the interferon alfa group (5 months), corresponding to a hazard ratio of 0.42 (95% confidence interval, 0.32 to 0.54; P<0.001). Sunitinib was also associated with a higher objective response rate than was interferon alfa (31% vs. 6%, P<0.001). The proportion of patients with grade 3 or 4 treatment-related fatigue was significantly higher in the group treated with interferon alfa, whereas diarrhea was more frequent in the sunitinib group (P<0.05). Patients in the sunitinib group reported a significantly better quality of life than did patients in the interferon alfa group (P<0.001).

Conclusions: Progression-free survival was longer and response rates were higher in patients with metastatic renal-cell cancer who received sunitinib than in those receiving interferon alfa (ClinicalTrials.gov numbers, NCT00098657 and NCT00083889 [ClinicalTrials.gov]).

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / secondary
  • Disease Progression
  • Female
  • Humans
  • Indoles / adverse effects
  • Indoles / therapeutic use*
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use*
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use*
  • Quality of Life
  • Receptors, Platelet-Derived Growth Factor / antagonists & inhibitors
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Risk Factors
  • Sunitinib

Substances

  • Angiogenesis Inhibitors
  • Indoles
  • Interferon-alpha
  • Protein Kinase Inhibitors
  • Pyrroles
  • Receptors, Platelet-Derived Growth Factor
  • Receptors, Vascular Endothelial Growth Factor
  • Sunitinib

Associated data

  • ClinicalTrials.gov/NCT00083889
  • ClinicalTrials.gov/NCT00098657