%0 Journal Article
%A Serrano, C.
%A Bauer, S.
%A Gómez-Peregrina, D.
%A Kang, Y-K
%A Jones, R. L.
%A Rutkowski, P.
%A Mir, O.
%A Heinrich, M. C.
%A Tap, W. D.
%A Newberry, K.
%A Grassian, A.
%A Shi, H.
%A Bialick, S.
%A Schöffski, P.
%A Pantaleo, M. A.
%A von Mehren, M.
%A Trent, J. C.
%A George, S.
%T Circulating tumor DNA analysis of the phase III VOYAGER trial: KIT mutational landscape and outcomes in patients with advanced gastrointestinal stromal tumor treated with avapritinib or regorafenib.
%J Annals of oncology
%V 34
%N 7
%@ 0923-7534
%C Amsterdam [u.a.
%I Elsevier
%M DKFZ-2023-00835
%P 615-625
%D 2023
%Z 2023 Jul;34(7):615-625
%X The current treatment paradigm of imatinib-resistant metastatic gastrointestinal stromal tumor (GIST) does not incorporate KIT/PDGFRA genotypes in therapeutic drug sequencing, except for PDGFRA exon 18-mutant GIST that are indicated for avapritinib treatment. Here, ctDNA sequencing was used to analyze plasma samples prospectively collected in the phase III VOYAGER trial to understand how the KIT/PDGFRA mutational landscape contributes to tyrosine-kinase inhibitor (TKI) resistance and to determine its clinical validity and utility.VOYAGER (N=476) compared avapritinib with regorafenib in patients with KIT/PDGFRA-mutant GIST previously treated with imatinib and 1 or 2 additional TKIs (NCT03465722). KIT/PDGFRA ctDNA mutation profiling of plasma samples at baseline and end-of-treatment was assessed with 74-gene Guardant360® CDx. Molecular subgroups were determined and correlated with outcomes.386/476 patients with KIT/PDGFRA-mutant tumors underwent baseline (pre-trial treatment) ctDNA analysis; 196 received avapritinib, and 190 received regorafenib. KIT and PDGFRA mutations were detected in 75.1
%K Avapritinib (Other)
%K GIST (Other)
%K KIT (Other)
%K PDGFRA (Other)
%K ctDNA (Other)
%K regorafenib (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37105265
%R 10.1016/j.annonc.2023.04.006
%U https://inrepo02.dkfz.de/record/275647