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

Ronald P. DeMatteo, Karla V. Ballman, Cristina R. Antonescu, Robert G. Maki, Peter WT Pisters, George D. Demetri, Martin E. Blackstein, Charles Blanke, Margaret von Mehren, Murray F. Brennan, Shreyaskumar Patel, Martin D. McCarter, Jonathan A. Polikoff, Benjamin R. Tan, Kouros Owzar

Research output: Contribution to journalArticle

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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 α 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

Original languageEnglish (US)
Pages (from-to)1097-1104
Number of pages8
JournalThe Lancet
Volume373
Issue number9669
DOIs
StatePublished - 2009
Externally publishedYes

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Gastrointestinal Stromal Tumors
Placebos
Recurrence
Survival
Platelet-Derived Growth Factor Receptors
Numismatics
Therapeutics
Survival Analysis
Sarcoma
Multicenter Studies
Imatinib Mesylate
Neoplasms
Proteins
Immunohistochemistry
Research Personnel

ASJC Scopus subject areas

  • Medicine(all)

Cite this

DeMatteo, R. P., Ballman, K. V., Antonescu, C. R., Maki, R. G., Pisters, P. WT., Demetri, G. D., ... Owzar, K. (2009). Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. The Lancet, 373(9669), 1097-1104. https://doi.org/10.1016/S0140-6736(09)60500-6

Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour : a randomised, double-blind, placebo-controlled trial. / DeMatteo, Ronald P.; Ballman, Karla V.; Antonescu, Cristina R.; Maki, Robert G.; Pisters, Peter WT; Demetri, George D.; Blackstein, Martin E.; Blanke, Charles; von Mehren, Margaret; Brennan, Murray F.; Patel, Shreyaskumar; McCarter, Martin D.; Polikoff, Jonathan A.; Tan, Benjamin R.; Owzar, Kouros.

In: The Lancet, Vol. 373, No. 9669, 2009, p. 1097-1104.

Research output: Contribution to journalArticle

DeMatteo, RP, Ballman, KV, Antonescu, CR, Maki, RG, Pisters, PWT, Demetri, GD, Blackstein, ME, Blanke, C, von Mehren, M, Brennan, MF, Patel, S, McCarter, MD, Polikoff, JA, Tan, BR & Owzar, K 2009, 'Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial', The Lancet, vol. 373, no. 9669, pp. 1097-1104. https://doi.org/10.1016/S0140-6736(09)60500-6
DeMatteo, Ronald P. ; Ballman, Karla V. ; Antonescu, Cristina R. ; Maki, Robert G. ; Pisters, Peter WT ; Demetri, George D. ; Blackstein, Martin E. ; Blanke, Charles ; von Mehren, Margaret ; Brennan, Murray F. ; Patel, Shreyaskumar ; McCarter, Martin D. ; Polikoff, Jonathan A. ; Tan, Benjamin R. ; Owzar, Kouros. / Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour : a randomised, double-blind, placebo-controlled trial. In: The Lancet. 2009 ; Vol. 373, No. 9669. pp. 1097-1104.
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AU - DeMatteo, Ronald P.

AU - Ballman, Karla V.

AU - Antonescu, Cristina R.

AU - Maki, Robert G.

AU - Pisters, Peter WT

AU - Demetri, George D.

AU - Blackstein, Martin E.

AU - Blanke, Charles

AU - von Mehren, Margaret

AU - Brennan, Murray F.

AU - Patel, Shreyaskumar

AU - McCarter, Martin D.

AU - Polikoff, Jonathan A.

AU - Tan, Benjamin R.

AU - Owzar, Kouros

PY - 2009

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