Dematteo RP, Ballman KV, Antonescu CR, et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial

Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
The Lancet (Impact Factor: 45.22). 03/2009; 373(9669):1097-104. DOI: 10.1016/S0140-6736(09)60500-6
Source: PubMed


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, 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.

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    • "Treatment of GIST patients harboring c-kit or PDGFRA mutations, with tyrosine kinase inhibitors such as imatinib and sunitinib, has been proven to be effective in cases of inoperable or metastatic tumors. As adjuvant imatinib treatment significantly improves recurrence-free survival [77] "
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    • "The early results suggest that molecular therapy with the tyrosine kinase inhibitor, imitanib mesylate, may play an important role as adjuvant therapy following GIST resection. It increases recurrence –free survival as shown by contrast enhanced CT scanning [12,13]. "
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    • "Surgery remains the standard and curative treatment of choice for patients with a resectable GIST. Target therapy using imatinib mesylate, a KIT receptor inhibitor, is indicated in those with advanced or unresectable GIST, or in high-risk patients after surgery as an adjuvant therapy [4,5]. However, acquired or secondary resistance to imatinib may occur in GIST patients under imatinib treatment for disease recurrence or progression [6,7]. "
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