Ontology highlight
ABSTRACT: Purpose
Most gastrointestinal stromal tumors (GIST) have activating mutations of KIT, PDGFRA, or uncommonly BRAF. Fifteen percent of adult and 85% of pediatric GISTs are wild type (WT), commonly having high expression of IGF-1R and loss of succinate dehydrogenase (SDH) complex function. We tested the efficacy of linsitinib, an oral TKI IGF-1R inhibitor, in patients with WT GIST.Patients and methods
A multicenter phase II trial of linsitinib was conducted. The primary endpoint was objective response rate. Secondary endpoints were clinical benefit rate: complete response, partial response, and stable disease (SD) ? 9 months, and quantitative 2[18F]fluoro-2-deoxy-D-glucose (FDG) metabolic response (MR) at week 8. Serum levels for glucose, insulin, IGF-1R ligand IGF1, and binding proteins were obtained to explore correlations to patient outcomes and FDG-PET results.Results
Twenty patients were accrued in a 6-month period. Grade 3-4 toxicities possibly related to linsitinib were uncommon (8.5%). No objective responses were seen. Clinical benefit rate (CBR) at 9 months was 40%. Intense FDG uptake was observed at baseline, with partial MR of 12% and stable metabolic disease of 65% at week 8; these patients had RECIST 1.1 SD as their best response. Progression-free survival (PFS) and overall survival Kaplan-Meier estimates at 9 months were 52% and 80%, respectively. SDHA/B loss determined by IHC was seen in 35% and 88% of cases, respectively.Conclusions
Linsitinib is well tolerated in patients with WT GIST. Although the 9-month CBR was 40%, and PFS at 9 months was 52%, no objective responses were observed. Rapid accrual to this study demonstrates that clinical trials of experimental agents in selected subtypes of GIST are feasible.
SUBMITTER: von Mehren M
PROVIDER: S-EPMC7856429 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
von Mehren Margaret M George Suzanne S Heinrich Michael C MC Schuetze Scott M SM Yap Jeffrey T JT Yu Jain Q JQ Abbott Amanda A Litwin Samuel S Crowley John J Belinsky Martin M Janeway Katherine A KA Hornick Jason L JL Flieder Douglas B DB Chugh Rashmi R Rink Lori L Van den Abbeele Annick D AD
Clinical cancer research : an official journal of the American Association for Cancer Research 20191202 8
<h4>Purpose</h4>Most gastrointestinal stromal tumors (GIST) have activating mutations of <i>KIT, PDGFRA</i>, or uncommonly <i>BRAF</i>. Fifteen percent of adult and 85% of pediatric GISTs are wild type (WT), commonly having high expression of IGF-1R and loss of succinate dehydrogenase (SDH) complex function. We tested the efficacy of linsitinib, an oral TKI IGF-1R inhibitor, in patients with WT GIST.<h4>Patients and methods</h4>A multicenter phase II trial of linsitinib was conducted. The primar ...[more]