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

Abstract

On December 19, 2008, the U.S. Food and Drug Administration approved imatinib mesylate tablets for oral use (Gleevec®; 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 endpoint. 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.