Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial

Dematteo, R. P., Ballman, K. V., Antonescu, C. R., Maki, R. G., Pisters, P. W., Demetri, G. D., Blackstein, M. E., Blanke, C. D., von Mehren, M., Brennan, M. F., Patel, S., McCarter, M. D., Polikoff, J. A., Tan, B. R., Owzar, K., American College of Surgeons Oncology Group Intergroup Adjuvant, Gist Study Team (March 2009) Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet, 373 (9669). pp. 1097-104. ISSN 1474-547X (Electronic)0140-6736 (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/19303137
DOI: 10.1016/S0140-6736(09)60500-6

Abstract

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: Adjuvant imatinib therapy is safe and seems to improve recurrence-free survival compared with placebo after the resection of primary gastrointestinal stromal tumour. FUNDING: US National Institutes of Health and Novartis Pharmaceuticals.

Item Type: Paper
Uncontrolled Keywords: Adolescent Adult Aged Aged, 80 and over Antineoplastic Agents/*administration & dosage/adverse effects Benzamides Chemotherapy, Adjuvant Double-Blind Method Female Gastrointestinal Stromal Tumors/mortality/pathology/surgery/*therapy Humans Imatinib Mesylate Male Middle Aged Piperazines/*administration & dosage/adverse effects Pyrimidines/*administration & dosage/adverse effects
Subjects: diseases & disorders > cancer > drugs and therapies
diseases & disorders > cancer > cancer types > gastrointestinal stromal tumors
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matt Covey
Date: 28 March 2009
Date Deposited: 25 Oct 2016 18:54
Last Modified: 25 Oct 2016 18:54
PMCID: PMC2915459
Related URLs:
URI: http://repository.cshl.edu/id/eprint/33695

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