Rechallenge with imatinib in advanced gastrointestinal stromal tumors: clinical implications of the RIGHT trial

Abstract

Tyrosine kinase inhibitors (TKIs) are the mainstay of the management of advanced gastrointestinal stromal tumors (GISTs). Currently, imatinib, sunitinib and regorafenib are approved treatments for advanced GISTs. However, most standard therapies eventually stop working due to polyclonal evolution of the disease, which results in TKI resistance and overall disease progression. For patients with refractory GISTs after progression on all approved TKIs, resumption of previously effective TKIs may have clinical benefit. However, no randomized trial had been performed to support TKI reuse in patients with advanced GISTs. Recently, a placebo-controlled randomized Phase III trial (RIGHT) found that imatinib resumption significantly prolonged progression-free survival in patients with TKI-refractory GISTs versus placebo. The details of the RIGHT trial and its clinical implications are reviewed here.