Systemic therapy of advanced/metastatic gastrointestinal stromal tumours: an update on progress beyond imatinib, sunitinib and regorafenib.

Systemic therapy of advanced/metastatic gastrointestinal stromal tumours: an update on progress beyond imatinib, sunitinib and regorafenib. Expert Opin Investig Drugs. 2020 Nov 30;: Authors: Mohammadi M, Gelderblom H Abstract Introduction Discovery of oncogenic mutations in the KIT and PDGFRA tyrosine kinase receptor was a crucial step for development of tyrosine kinase inhibitors (TKI's). Since then, GIST became a model for development of molecular targeted therapy, which led to dramatically improved median overall survival of advanced GIST . Still further progress is needed after third line or for TKI resistant mutations. Areas covered In this review, after a brief introduction of imatinib, sunitinib an regorafenib an overview of TKI's that were evaluated beyond these drugs is provided, with a main focus on the novel approved TKI's. Expert opinion Combination therapies have thus far not fulfilled their promise in GIST, nor did immunotherapy. Increased understanding of GIST and advances in development of molecular targeted drugs led to introduction of ripretinib and avapritinib. Furthermore, NTRK inhibitors became available for ultrarare NTRK fusions. Solutions for NF1 and BRAF mutated and SDH-deficient GIST are still to be awaited. This all underlines the need for adequate molecular profiling of high risk GISTs before treatment is started. Possibly by using circulating tumour DNA in the future, targeting resistance mutations with s...
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research