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(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 endpoint. Eligible patients were > or =18 years of age with a histological diagnosis of GIST (Kit(+)), resected tumor size > or =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 > or =3 adverse reactions. The most frequently reported adverse reactions (> or =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.

• Authors: Martin H Cohen, Patricia Cortazar, Robert Justice, Richard Pazdur
• Journal: The oncologist (Oncologist) Vol. 15 Issue 3 Pg. 300-7 ( 2010) ISSN: 1549-490X [Electronic] England
• PMID: 20200041 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)

Chemical References

• Antineoplastic Agents
• Benzamides
• Piperazines
• Pyrimidines
• Imatinib Mesylate

Topics

• Aged
• Antineoplastic Agents (adverse effects, therapeutic use)
• Benzamides
• Chemotherapy, Adjuvant
• Disease-Free Survival
• Double-Blind Method
• Drug Approval
• Female
• Gastrointestinal Stromal Tumors (drug therapy, pathology, surgery)
• Humans
• Imatinib Mesylate
• Male
• Middle Aged
• Piperazines (adverse effects, therapeutic use)
• Pyrimidines (adverse effects, therapeutic use)
• Treatment Outcome