TY  - JOUR
AU  - Serrano, C.
AU  - Bauer, S.
AU  - Gómez-Peregrina, D.
AU  - Kang, Y-K
AU  - Jones, R. L.
AU  - Rutkowski, P.
AU  - Mir, O.
AU  - Heinrich, M. C.
AU  - Tap, W. D.
AU  - Newberry, K.
AU  - Grassian, A.
AU  - Shi, H.
AU  - Bialick, S.
AU  - Schöffski, P.
AU  - Pantaleo, M. A.
AU  - von Mehren, M.
AU  - Trent, J. C.
AU  - George, S.
TI  - 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.
JO  - Annals of oncology
VL  - 34
IS  - 7
SN  - 0923-7534
CY  - Amsterdam [u.a.
PB  - Elsevier
M1  - DKFZ-2023-00835
SP  - 615-625
PY  - 2023
N1  - 2023 Jul;34(7):615-625
AB  - 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
KW  - Avapritinib (Other)
KW  - GIST (Other)
KW  - KIT (Other)
KW  - PDGFRA (Other)
KW  - ctDNA (Other)
KW  - regorafenib (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37105265
DO  - DOI:10.1016/j.annonc.2023.04.006
UR  - https://inrepo02.dkfz.de/record/275647
ER  -