Open AccessApproval Summary: Imatinib Mesylate in the Adjuvant Treatment of Malignant Gastrointestinal Stromal Tumors
Author(s) -
Cohen Martin H.,
Cortazar Patricia,
Justice Robert,
Pazdur Richard
Publication year - 2010
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2009-0120
Subject(s) - medicine , adverse effect , imatinib mesylate , nausea , placebo , gist , imatinib , clinical endpoint , gastroenterology , hazard ratio , rash , vomiting , interim analysis , surgery , clinical trial , confidence interval , pathology , stromal cell , alternative medicine , myeloid leukemia
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.