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Adjuvant Imatinib for GIST: Promising
Abstract & Commentary
By William B. Ershler, MD, Editor, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.
Synopsis: Imatinib mesylate has proven effective in the management of advanced gastrointestinal stromal tumors, but its use in the adjuvant setting is yet to be established. The current report details the experience from a single institution at which imatinib (400 orally/day) was administered for one year after radical surgery in patients considered at high-risk for recurrence. Compared to historical controls, recurrence rate was dramatically reduced. Confirmation of these findings await the results from ongoing randomized, prospective trials.
Source: Nilsson B, et al. Adjuvant imatinib treatment improves recurrence-free survival in patients with high-risk gastrointestinal stromal tumors (GIST). Br J Cancer. 2007;96:1656-1658.
Imatinib mesylate treatment for patients with advanced gastrointestinal stromal cell tumors (GIST), particularly those with KIT exon 11 mutations has been demonstrated to provide excellent therapeutic value1 in terms of remission rates and overall survival. However, its efficacy in the adjuvant setting has not been established. To address this, Nilsson and colleagues in Göteborg, Sweden reviewed their single institution experience.
Twenty-three consecutive patients (mean age, 56 years; range 21-82 years) diagnosed with high-risk GIST between February 2001 and June 2005 received imatinib mesylate (400 mg orally/day for one year) after radical tumor resection. Of the 23, 19 (83%) had tumors with mutations in KIT or PDGFRA (platelet-derived growth factor receptor α). The mean tumor size was 9.4 cm (range 2-35 cm) and the mean Ki67 max % (ie, maximum percentage of cells positive with Ki67 immunostains) was 7.0 (s.d., 5; range 2-10%). The mean follow-up after imatinib treatment was 40 months (range 18-62 months). For comparison, the clinical outcomes of 48 patients (mean age 67 years, range 25-87 years) detailed in a prior series of GIST2,3, matched for "high-risk" features (tumor size, max % Ki67) were examined. In that series, patients were not treated in the adjuvant setting, but were followed carefully for the occurrence of recurrent disease. For this group of historical controls, the mean tumor size was 12.3 cm (range 3.5-33 cm) and mean Ki67 max % was 11.7 (s.d. 11.8, range 0.5-40%). These patients had a mean follow-up of 36 months (range 2-151 months). Of the 48, 30 (63%) had tumors with mutations in KIT or PDGFRA.
Only one of the 23 patients receiving adjuvant imatinib therapy developed recurrence, and this was 22 months after completing the one year of adjuvant therapy. In contrast 32 of the 48 patients (67%) in the control group developed recurrent disease.
These findings lend strong rationale to the use of imatinib in the setting of high risk, post resection GIST management. However, caution must be exercised in retrospective comparisons. The groups were not quite comparable (patients were somewhat older, with larger tumors and with fewer KIT mutations). Yet, one cannot help but be optimistic that these findings will be confirmed in prospective, controlled trials. In that regard, it is worthy of mention that several such trials are underway. One trial (ACOSOG Z9001) compares imatinib treatment (400 mg/day for one year) with placebo in patients with resected tumors ≥ 3cm. The EORTC (trial 62024) examines imatinib treatment (400 mg/day) vs placebo for intermediate and high-risk patients for a duration of two years, and SSG XVIII examines imatinib treatment (400 mg/day) for either one or three years in those with high risk.
The current retrospective analysis is the first in what is likely to be a series of publications on the value of imatinib for selected patients with intermediate or high-risk GIST. However, with the high response rate demonstrated in the palliative setting, it will take additional studies to determine whether the benefits of treatment in the adjuvant setting will translate to overall improved survival.
1. Verweij J, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004;364(9440):1127-1134.
2. Bumming P, et al. Population-based study of the diagnosis and treatment of gastrointestinal stromal tumours. Br J Surg. 2006;93(7):836-843.
3. Nilsson B, et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era—a population-based study in western Sweden. Cancer. 2005;103(4):821-829.