Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial Journal Article
| Authors: | 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. |
| Article Title: | Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial |
| 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<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. © 2009 Elsevier Ltd. All rights reserved. |
| Keywords: | immunohistochemistry; adolescent; adult; cancer survival; controlled study; aged; aged, 80 and over; middle aged; cancer surgery; primary tumor; major clinical study; clinical trial; drug tolerability; fatigue; neutropenia; cancer recurrence; placebo; diarrhea; drug efficacy; drug safety; drug withdrawal; side effect; antineoplastic agents; chemotherapy, adjuvant; follow up; gastrointestinal stromal tumor; imatinib; stem cell factor receptor; gastrointestinal stromal tumors; edema; controlled clinical trial; tumor volume; randomized controlled trial; pyrimidines; abdominal pain; alanine aminotransferase blood level; aspartate aminotransferase blood level; dyspnea; hyperglycemia; syncope; hypokalemia; multicenter study; tumor recurrence; nausea and vomiting; dermatitis; phase 3 clinical trial; piperazines; crossover procedure; double blind procedure; double-blind method |
| Journal Title: | Lancet |
| Volume: | 373 |
| Issue: | 9669 |
| ISSN: | 0140-6736 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2009-03-28 |
| Start Page: | 1097 |
| End Page: | 1104 |
| Language: | English |
| DOI: | 10.1016/s0140-6736(09)60500-6 |
| PUBMED: | 19303137 |
| PROVIDER: | scopus |
| PMCID: | PMC2915459 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 80" - "Export Date: 30 November 2010" - "CODEN: LANCA" - "Source: Scopus" |
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