Imatinib as adjuvant therapy for gastrointestinal stromal tumors: a systematic review

The high risk of recurrence in resected gastrointestinal stromal tumor (GIST) highlights the need for effective adjuvant treatment. This review evaluates the clinical efficacy and safety of imatinib for adjuvant treatment of localized KIT (CD117)-positive resected GIST. Relevant studies were identified by searching several electronic databases from inception to August 2009. Searches were supplemented by examining bibliographies of included studies, searching conference proceedings and consulting experts. All study types were included. Methodological quality was assessed using published criteria. Sixteen studies met the eligibility criteria, comprising one randomized controlled trial (RCT), three phase II studies, three cohort studies and nine case reports. In the RCT, the estimated 1-year recurrence-free survival was 98% [95% confidence interval (CI), 96-100] in the imatinib group versus 83% (95% CI, 78-88) in the placebo group, corresponding to a 65% reduction in the risk of disease recurrence (hazard ratio, 0.35; 95% CI, 0.22-0.53; p < 0.0001) with an absolute recurrence-free survival difference of 15% at 1 year. Other nonrandomized studies reported similar outcomes demonstrating that imatinib used in the adjuvant setting improved recurrence-free survival. The optimum duration of adjuvant treatment, safety and efficacy is currently under investigation with two ongoing RCTs (EORTC 62024 and SSG XV111) and two nonrandomized studies (NCT00867113 and NCT00171977). This study adds to the evidence (based on one RCT and a number of observational studies) that GIST patients treated with adjuvant imatinib therapy show an improvement in recurrence-free survival compared to placebo or no treatment after resection of KIT-positive localized GIST with tolerable toxicity.