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N Engl J Med. 2016 Dec 8;375(23):2246-2254. Epub 2016 Oct 9.

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

Author information

1
From the Department of Medical Oncology, Bordeaux University Hospital, Bordeaux (A.R.), Department of Medical Oncology, Institut Gustave Roussy, Villejuif (B.E.), Medical Oncology, Centre Eugene Marquis, Rennes (B.L.), and Department of Urology, Bicêtre Hospital, Paris-Saclay University, Le Kremlin Bicêtre (J.-J.P.) - all in France; Department of Medicine, Memorial Sloan Kettering Cancer Center (R.J.M.), and Pfizer (K.R.) - both in New York; Department of Clinical and Experimental Medicine, University of Surrey, Surrey, United Kingdom (H.S.P.); Division of Medical Oncology, Duke Cancer Institute, Durham, NC (D.J.G.); Department of Urology, Ronald Reagan UCLA Medical Center, Los Angeles (A.J.P.), and Pfizer, La Jolla (X.L., J.-F.M.) - both in California; Spire Roding Hospital, London (A.P.); Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan (Y.-H.C.); Department of Oncology, Aarhus University Hospital, Aarhus, Denmark (F.D.); Department of Urology, Charité Universitätsmedizin Berlin, Berlin (A.M.), and Department of Urology, University Hospital of Munich, Munich (M.S.) - both in Germany; Divisions of Oncology and Urology, Azienda Ospedaliera di Rilievo Nazionale A. Cardarelli, Naples, Italy (G.C.); Klinika Onkologii Oddzial Chemioterapii, Poznan, Poland (P.T.); Department of Urology, Slovak Medical University, Bratislava, Slovakia (J.B.); and Pfizer, Milan (P.G., M.L.), and Collegeville, PA (M.C.).

Abstract

BACKGROUND:

Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy.

METHODS:

In this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, 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 or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety.

RESULTS:

The 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 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in 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 similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects.

CONCLUSIONS:

Among patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. (Funded by Pfizer; S-TRAC ClinicalTrials.gov number, NCT00375674 .).

PMID:
27718781
DOI:
10.1056/NEJMoa1611406
[Indexed for MEDLINE]
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