Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy

BACKGROUNDSunitinib, a vascular endothelial growth factor pathway inhibitor, is an effectivetreatment for metastatic renal-cell carcinoma. We sought to determine the efficacyand safety of sunitinib in patients with locoregional renal-cell carcinoma athigh risk for tumor recurrence after nephrectomy.METHODSIn this randomized, double-blind, phase 3 trial, we assigned 615 patients withlocoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib(50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year oruntil disease recurrence, unacceptable toxicity, or consent withdrawal. The primaryend point was disease-free survival, according to blinded independent central review.Secondary end points included investigator-assessed disease-free survival,overall survival, and safety.RESULTSThe median duration of disease-free survival was 6.8 years (95% confidence interval[CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overallsurvival data were not mature at the time of data cutoff. Dose reductions becauseof adverse events were more frequent in the sunitinib group than in theplacebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) anddiscontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequentin the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events)than in the placebo group (15.8% and 3.6%, respectively). There was a similarincidence of serious adverse events in the two groups (21.9% for sunitinib vs.17.1% for placebo); no deaths were attributed to toxic effects.CONCLUSIONSAmong patients with locoregional clear-cell renal-cell carcinoma at high risk fortumor recurrence after nephrectomy, the median duration of disease-free survivalwas significantly longer in the sunitinib group than in the placebo group, at a costof a higher rate of toxic events. (Funded by Pfizer; S-TRAC ClinicalTrials.gov number,NCT00375674.)