Approval Summary: Imatinib Mesylate in the Adjuvant Treatment of Malignant Gastrointestinal Stromal Tumors

On December 19, 2008, the U. S. Food and Drug Administration approved imatinib mesylate tablets for oral use (Gleevec (R); Novartis Pharmaceuticals Corporation, East Hanover, NJ) for the adjuvant treatment of adult patients following complete gross resection of Kit(+) (CD117(+)) gastrointestinal stromal tumor (GIST). A randomized, double-blind, placebo-controlled study enrolling 713 patients was submitted. The primary objective of the clinical trial was to compare the recurrence-free survival (RFS) intervals of the two groups. Overall survival (OS) was a secondary end-point. Eligible patients were >= 18 years of age with a histological diagnosis of GIST (Kit(+)), resected tumor size >= 3 cm, and a complete gross resection within 14-70 days prior to registration. Imatinib, 400 mg orally, was administered once daily for 1 year. The study was terminated after completion of the third protocol-specified interim analysis. At that time, 100 RFS events were confirmed by a blinded central independent review. With a median follow-up of 14 months, 30 RFS events were observed in the imatinib group and 70 were observed in the placebo group (hazard ratio, 0.398; 95% confidence interval, 0.259-0.610; two-sided p-value < .0001). OS results are immature. Most patients in both groups experienced at least one adverse reaction, and 31% of the imatinib group and 18% of the placebo group experienced grade >= 3 adverse reactions. The most frequently reported adverse reactions (>= 20%) were diarrhea, fatigue, nausea, edema, decreased hemoglobin, rash, vomiting, and abdominal pain. Drug was discontinued for adverse reactions in 17% and 3% of the imatinib and placebo-treated patients, respectively. The Oncologist 2010; 15: 300-307