Optimising therapy for GIST patients

Abstract

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive tract, although their incidence is low. Management of GIST patients has evolved rapidly following discovery of the role of constitutively activated KIT tyrosine kinase in GIST oncogenesis. Elucidation of the oncogenic mechanism for GIST formed the basis for immunohistochemical diagnosis of GIST as well as for treatment by molecular targeting with the tyrosine kinase inhibitor imatinib. Imatinib has been shown in clinical trials to be efficacious and well tolerated for treatment of unresectable or metastatic GIST. Trial data show that median survival has not yet been reached at more than 3 years of imatinib therapy for patients with advanced GIST, an improvement of at least 2 years over previous therapy. Advancements in the diagnosis and treatment of GIST provide the basis for key strategies to optimise management. These strategies include the use of imaging in assessment and optimisation of therapeutic response, management of imatinib toxicity, optimisation of dose, and duration of therapy. Imatinib should be administered initially at 400 mg or 600 mg/day until signs of progression. Recent studies have revealed a relationship between KIT mutation genotype and response to imatinib therapy. Dose escalation should be instituted after an evaluation for potential underlying causes of low drug exposure. This review summarises developments in the treatment of GIST and the consensus on management with the goal of optimising patient care.