Authors: Tiffany Foo, David Goldstein, Eva Segelov, Jeremy Shapiro, Nick Pavlakis, Jayesh Desai, Desmond Yip, John Zalcberg, Timothy J. Price, Adnan Nagrial, Lorraine Chantrill, Matt Burge, Christos S. Karapetis, Niall Tebbutt & Amitesh C. Roy
Abstract
Gastrointestinal stromal tumours (GISTs) are the most common gastrointestinal tract mesenchymal tumours. Tyrosine kinase inhibitors (TKIs) have transformed the management of advanced GIST. Imatinib was the first TKI to gain approval as management for patients with advanced GIST, establishing a new standard of care. Since then, as a result of several trials including the GRID and INVICTUS studies, we now have five lines of approved targeted therapy, including imatinib, sunitinib, regorafenib, ripretinib and avapritinib for the treatment of unresectable, advanced GISTs. In this review, the Australasian Gastrointestinal Trials Group (AGITG) provide an overview of the key trials that have changed clinical practice, discuss the molecular drivers of GISTs, the importance of molecular testing and directing therapy according to molecular targets, as well as future strategies in the management of advanced GISTs.
Key Points |
The development of tyrosine kinase inhibitors (TKIs) has led to significant improvements in the management of inoperable, advanced gastrointestinal stromal tumours. |
Despite an initial response to TKIs, disease progression often occurs due to resistance mutations. |
Next-generation TKIs targeting secondary KIT mutations and other therapeutic targets are being investigated to overcome these resistance mutations. |