Next questions for the medical treatment of gastrointestinal stromal tumor.

Abstract

Since its approval in 2002, imatinib remains the standard first-line treatment for patients with advanced gastrointestinal stromal tumors (GISTs). Overall, all the drugs approved for patients who have developed secondary resistance to imatinib are less effective than imatinib in first-line. Even if, overall survival of patients with advanced GIST has improved over time the last 20 years, imatinib-resistant GIST remains therefore a difficult-to-treat cancer. The aim of this review is to elaborate on the potential strategies to improve outcome for patients with imatinib-refractory disease. New-generation potent KIT and PDGFRA inhibitors such as ripretinib and avapritinib developed for the treatment of GIST have shown very promising clinical activity in patients with highly refractory disease. However, both failed to improve outcome in comparison with standard of care in earlier lines settings. Clinical trials investigating the efficacy of multikinase inhibitor with highly specific KIT inhibitors are currently ongoing. Targeting the microenvironment of GIST may also represent a promising approach and is investigated in several clinical studies. Imatinib-refractory GIST still represent a therapeutic challenge. It is likely that only combination therapies with new generation of tyrosine kinase inhibitors (TKIs) and/or immune-oncology agents might potentially result in an enhanced therapeutic efficacy compared with current standard of care.