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

• Published in: The Lancet (British edition) 2009-03, Vol.373 (9669), p.1097-1104
• Main Authors: DeMatteo, Ronald P, Prof, Ballman, Karla V, PhD, Antonescu, Cristina R, MD, Maki, Robert G, MD, Pisters, Peter WT, Prof, Demetri, George D, MD, Blackstein, Martin E, MD, Blanke, Charles D, Prof, von Mehren, Margaret, MD, Brennan, Murray F, Prof, Patel, Shreyaskumar, Prof, McCarter, Martin D, MD, Polikoff, Jonathan A, MD, Tan, Benjamin R, MD, Owzar, Kouros, PhD
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Benzamides; Biological and medical sciences; Cancer; Chemotherapy; Chemotherapy, Adjuvant; Dermatitis; Double-Blind Method; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gastrointestinal Stromal Tumors - mortality; Gastrointestinal Stromal Tumors - pathology; Gastrointestinal Stromal Tumors - surgery; Gastrointestinal Stromal Tumors - therapy; General aspects; Health services; Humans; Imatinib Mesylate; Internal Medicine; Male; Medical sciences; Medical treatment; Middle Aged; Mutation; Oncology; Patient care planning; Patients; Physical examinations; Piperazines - administration & dosage; Piperazines - adverse effects; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Sarcoma; Small intestine; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Studies; Survival; Tumors
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(09)60500-6

Summary 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