Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma.

Abstract

PURPOSE:

A randomized, phase III trial demonstrated superiority of sunitinib over interferon alfa (IFN-alpha) in progression-free survival (primary end point) as first-line treatment for metastatic renal cell carcinoma (RCC). Final survival analyses and updated results are reported.

PATIENTS AND METHODS:

Seven hundred fifty treatment-naïve patients with metastatic clear cell RCC were randomly assigned to sunitinib 50 mg orally once daily on a 4 weeks on, 2 weeks off dosing schedule or to IFN-alpha 9 MU subcutaneously thrice weekly. Overall survival was compared by two-sided log-rank and Wilcoxon tests. Progression-free survival, response, and safety end points were assessed with updated follow-up.

RESULTS:

Median overall survival was greater in the sunitinib group than in the IFN-alpha group (26.4 v 21.8 months, respectively; hazard ratio [HR] = 0.821; 95% CI, 0.673 to 1.001; P = .051) per the primary analysis of unstratified log-rank test (P = .013 per unstratified Wilcoxon test). By stratified log-rank test, the HR was 0.818 (95% CI, 0.669 to 0.999; P = .049). Within the IFN-alpha group, 33% of patients received sunitinib, and 32% received other vascular endothelial growth factor-signaling inhibitors after discontinuation from the trial. Median progression-free survival was 11 months for sunitinib compared with 5 months for IFN-alpha (P < .001). Objective response rate was 47% for sunitinib compared with 12% for IFN-alpha (P < .001). The most commonly reported sunitinib-related grade 3 adverse events included hypertension (12%), fatigue (11%), diarrhea (9%), and hand-foot syndrome (9%).

CONCLUSION:

Sunitinib demonstrates longer overall survival compared with IFN-alpha plus improvement in response and progression-free survival in the first-line treatment of patients with metastatic RCC. The overall survival highlights an improved prognosis in patients with RCC in the era of targeted therapy.

• Authors: Robert J Motzer, Thomas E Hutson, Piotr Tomczak, M Dror Michaelson, Ronald M Bukowski, Stéphane Oudard, Sylvie Negrier, Cezary Szczylik, Roberto Pili, Georg A Bjarnason, Xavier Garcia-del-Muro, Jeffrey A Sosman, Ewa Solska, George Wilding, John A Thompson, Sindy T Kim, Isan Chen, Xin Huang, Robert A Figlin
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 22 Pg. 3584-90 (Aug 01 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19487381 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Indoles
• Interferon-alpha
• Pyrroles
• Sunitinib

Topics

• Administration, Oral
• Adult
• Aged
• Carcinoma, Renal Cell (drug therapy, mortality, secondary)
• Confidence Intervals
• Disease-Free Survival
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Indoles (administration & dosage, adverse effects)
• Injections, Subcutaneous
• Interferon-alpha (administration & dosage)
• Kaplan-Meier Estimate
• Kidney Neoplasms (drug therapy, mortality, pathology)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Invasiveness (pathology)
• Neoplasm Metastasis
• Neoplasm Staging
• Probability
• Proportional Hazards Models
• Pyrroles (administration & dosage, adverse effects)
• Sunitinib
• Survival Analysis
• Treatment Outcome