Placebo-Controlled Randomized Trial of Adjuvant Imatinib Mesylate Following the Resection of Localized, Primary Gastrointestinal Stromal Tumor (GIST)

By R. DeMatteo, K. Ballman, C. Antonescu, R. Maki, P. Pisters, G. Demetri, M. Blackstein, C. Blanke, M. von Mehren, M. Brennan and 5 more. The Lancet, 2009

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Background Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the intestinal tract. The standard treatment of localized, primary GIST has been surgical resection alone. Most GISTs have a mutation in the KIT proto-oncogene, or less commonly in platelet-derived growth factor receptor alpha (PDGFRα). Imatinib mesylate is a small molecule that inhibits activation of the KIT and PDGFRα proteins and is effective in metastatic GIST. We hypothesized that adjuvant treatment with imatinib would result in improved recurrence-free survival (RFS) compared to placebo treatment following resection of localized, primary GIST. Methods We performed a randomized phase 3, double-blind, placebo-controlled, multicenter trial. Eligible patients had complete gross resection of a primary GIST at least 3 cm in size that stained positive for KIT protein. Patients were randomly assigned to receive imatinib 400 mg/day or placebo daily for one year following surgical resection. Patients assigned to placebo were eligible to crossover to imatinib treatment in the event of tumor recurrence. The primary endpoint was RFS and intention to treat analysis was performed. This study is registered at ClinicalTrials.gov, number NCT00041197. Findings From July 2002 to April 2007, 359 patients were randomized to imatinib and 354 to placebo. Accrual was stopped early based on the results of a planned interim analysis. Imatinib significantly prolonged RFS compared with placebo (98% vs. 83% at 1 year; overall hazard ratio 0.35; one-sided p<0.0001). Overall survival (OS) was similar (99.2% vs. 99.7% at 1 year; hazard ratio 0.66; p=0.47). Adjuvant imatinib was well-tolerated with a low rate of serious adverse events. Interpretation Adjuvant imatinib therapy is safe and compared to placebo treatment appears to prolong RFS following the resection of primary GIST. OS is not different at this time.

Subfields: Gastroenterology, Surgery

View Paper: https://www.semanticscholar.org/paper/9489387fd10b8b8bad01ad8debfba5db75c0a5ed

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