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.

Fig 1.

Patient enrollment and outcomes. *Twenty-five patients from the IFN-α group crossed over to receive sunitinib on study. IFN-α, interferon alfa.

Fig 2.

Kaplan-Meier estimates of overall survival. IFN-α, interferon alfa.

Fig 3.

Overall survival subgroup analysis by individual baseline factors. Data are missing for 15 patients for time from diagnosis to treatment, 16 patients for hemoglobin and corrected serum calcium, and 17 patients for lactate dehydrogenase (LDH). IFN-α, interferon alfa; ECOG, Eastern Cooperative Oncology Group; ULN, upper limit of normal; LLN, lower limit of normal.