Imatinib rechallenge in patients with advanced gastrointestinal stromal tumors

Background: Imatinib is the standard of care for patients with advanced gastrointestinal stromal tumors (GIST). Design: This article reviews recent data on the impact of imatinib treatment interruption and subsequent rechallenge in patients with advanced GIST. Results: The randomized BFR14 trial showed that (i) interruption of imatinib after 1, 3, or 5 years of treatment in patients with nonprogressive GIST was associated with a high risk of progression even in patients with a complete response; (ii) rechallenge with imatinib restored tumor control in most patients, but the tumor response seldom reached that before treatment interruption; (iii) patients receiving continuous imatinib had a high rate of prolonged tumor control, which increased with longer imatinib treatment. The findings in the metastatic setting have important implications regarding the duration of adjuvant imatinib in GIST. Conclusions: Discontinuation of imatinib in responding patients with advanced GIST is associated with a high risk of progression and is therefore not recommended. Although rechallenge is a strategy for treating patients who relapse after stopping imatinib, suboptimal tumor response indicates that continuous kinase suppression is necessary to achieve the best clinical outcome. Three-year adjuvant imatinib is recommended for patients with resected 'high-risk' GIST; however, a longer duration may provide additional benefits.