Imatinib rechallenge in patients with advanced gastrointestinal stromal tumors

Imatinib is the standard of care for patients with advanced gastrointestinal stromal tumors (GIST). This article reviews recent data on the impact of imatinib treatment interruption and subsequent rechallenge in patients with advanced GIST. 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. 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.