Management of localized gastrointestinal stromal tumors and adjuvant therapy with imatinib

This review provides an overview of the use of the protein tyrosine kinase inhibitor imatinib as adjuvant therapy in patients with gastrointestinal stromal tumors (GISTs) at risk of recurrence after surgery. GISTs are the most common mesenchymal tumors of the gastrointestinal tract, and are characterized by the detection of KIT expression by immunohistochemistry in ~95% of the cases. The recommended treatment for localized GISTs is surgical excision, although there is a significant risk of recurrence after surgery. Accurate staging is an important step in identifying patients most at risk of tumor recurrence after surgery, and is based on a combination of tumor size, mitotic rate, and location. Other factors, including tumor rupture and the presence of mutations in the KIT and PDGFRA genes, also play an important role in the assessment of prognosis. A significant number of phase II studies have shown that 1 year of adjuvant therapy with 400 mg/day imatinib significantly reduces the recurrence of GISTs following surgery and extends recurrence-free survival, with evidence from the SSGXVIII/AIO study showing that extending the duration of adjuvant therapy to 3 years further increases recurrence-free and overall survival. Two currently ongoing trials, the EORTC 62024 and the PERSIST-5 trials, aim to strengthen the evidence that extending the duration of imatinib therapy beyond 1 year provides further benefits to patients in terms of reducing disease recurrence and increasing survival. In conclusion, imatinib significantly increases survival and reduces recurrence of GISTs in the adjuvant setting.