Gastrointestinal stromal tumour is the most common sarcoma of the intestinal tract.
Imatinib mesylate is a small molecule that inhibits activation of the KIT and platelet-derived
growth factor receptor alpha proteins, and is effective in first-line treatment of
metastatic gastrointestinal stromal tumour. We postulated that adjuvant treatment
with imatinib would improve recurrence-free survival compared with placebo after resection
of localised, primary gastrointestinal stromal tumour.
We undertook a randomised phase III, double-blind, placebo-controlled, multicentre
trial. Eligible patients had complete gross resection of a primary gastrointestinal
stromal tumour at least 3 cm in size and positive for the KIT protein by immunohistochemistry.
Patients were randomly assigned, by a stratified biased coin design, to imatinib 400
mg (n=359) or to placebo (n=354) daily for 1 year after surgical resection. Patients
and investigators were blinded to the treatment group. Patients assigned to placebo
were eligible to crossover to imatinib treatment in the event of tumour recurrence.
The primary endpoint was recurrence-free survival, and analysis was by intention to
treat. Accrual was stopped early because the trial results crossed the interim analysis
efficacy boundary for recurrence-free survival. This study is registered with ClinicalTrials.gov,
number NCT00041197.
All randomised patients were included in the analysis. At median follow-up of 19.7
months (minimum-maximum 0-56.4), 30 (8%) patients in the imatinib group and 70 (20%)
in the placebo group had had tumour recurrence or had died. Imatinib significantly
improved recurrence-free survival compared with placebo (98% [95% CI 96-100] vs 83%
[78-88] at 1 year; hazard ratio [HR] 0.35 [0.22-0.53]; one-sided p<0.0001). Adjuvant
imatinib was well tolerated, with the most common serious events being dermatitis
(11 [3%] vs 0), abdominal pain (12 [3%] vs six [1%]), and diarrhoea (ten [2%] vs five
[1%]) in the imatinib group and hyperglycaemia (two [<1%] vs seven [2%]) in the placebo
group.
Adjuvant imatinib therapy is safe and seems to improve recurrence-free survival compared
with placebo after the resection of primary gastrointestinal stromal tumour.
US National Institutes of Health and Novartis Pharmaceuticals.