Ripretinib versus sunitinib in gastrointestinal stromal tumor: ctDNA biomarker analysis of the phase 3 INTRIGUE trial

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dc.contributor.authorHeinrich, Michael C.
dc.contributor.authorJones, Robin L.
dc.contributor.authorGeorge, Suzanne
dc.contributor.authorGelderblom, Hans
dc.contributor.authorSchoeffski, Patrick
dc.contributor.authorvon Mehren, Margaret
dc.contributor.authorZalcberg, John R.
dc.contributor.authorKang, Yoon-Koo
dc.contributor.authorRazak, Albiruni Abdul
dc.contributor.authorTrent, Jonathan
dc.contributor.authorAttia, Steven
dc.contributor.authorLe Cesne, Axel
dc.contributor.authorSiontis, Brittany L.
dc.contributor.authorGoldstein, David
dc.contributor.authorBoye, Kjetil
dc.contributor.authorSanchez, Cesar
dc.contributor.authorSteeghs, Neeltje
dc.contributor.authorRutkowski, Piotr
dc.contributor.authorDruta, Mihaela
dc.contributor.authorSerrano, Cesar
dc.contributor.authorSomaiah, Neeta
dc.contributor.authorChi, Ping
dc.contributor.authorReichmann, William
dc.contributor.authorSprott, Kam
dc.contributor.authorAchour, Haroun
dc.contributor.authorSherman, Matthew L.
dc.contributor.authorRuiz-Soto, Rodrigo
dc.contributor.authorBlay, Jean-Yves
dc.contributor.authorBauer, Sebastian
dc.date.accessioned2025-01-20T17:10:17Z
dc.date.available2025-01-20T17:10:17Z
dc.date.issued2024
dc.description.abstractINTRIGUE was an open-label, phase 3 study in adult patients with advanced gastrointestinal stromal tumor who had disease progression on or intolerance to imatinib and who were randomized to once-daily ripretinib 150 mg or sunitinib 50 mg. In the primary analysis, progression-free survival (PFS) with ripretinib was not superior to sunitinib. In clinical and nonclinical studies, ripretinib and sunitinib have demonstrated differential activity based on the exon location of KIT mutations. Therefore, we hypothesized that mutational analysis using circulating tumor DNA (ctDNA) might provide further insight. In this exploratory analysis (N = 362), baseline peripheral whole blood was analyzed by a 74-gene ctDNA next-generation sequencing-based assay. ctDNA was detected in 280/362 (77%) samples with KIT mutations in 213/362 patients (59%). Imatinib-resistant mutations were found in the KIT ATP-binding pocket (exons 13/14) and activation loop (exons 17/18). Mutational subgroup assessment showed 2 mutually exclusive populations with differential treatment effects. Patients with only KIT exon 11 + 13/14 mutations (ripretinib, n = 21; sunitinib, n = 20) had better PFS with sunitinib versus ripretinib (median, 15.0 versus 4.0 months). Patients with only KIT exon 11 + 17/18 mutations (ripretinib, n = 27; sunitinib, n = 25) had better PFS with ripretinib versus sunitinib (median, 14.2 versus 1.5 months). The results of this exploratory analysis suggest ctDNA sequencing may improve the prediction of the efficacy of single-drug therapies and support further evaluation of ripretinib in patients with KIT exon 11 + 17/18 mutations. ClinicalTrials.gov identifier: NCT03673501.
dc.description.abstractExploratory ctDNA analyses from the phase 3 INTRIGUE trial indicate that ripretinib may provide benefits in patients with advanced gastrointestinal stromal tumors with KIT exon 11 + 17/18 mutations
dc.fuente.origenWOS
dc.identifier.doi10.1038/s41591-023-02734-5
dc.identifier.eissn1546-170X
dc.identifier.issn1078-8956
dc.identifier.urihttps://doi.org/10.1038/s41591-023-02734-5
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/91097
dc.identifier.wosidWOS:001137091500004
dc.issue.numero3
dc.language.isoen
dc.revistaNature medicine
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleRipretinib versus sunitinib in gastrointestinal stromal tumor: ctDNA biomarker analysis of the phase 3 INTRIGUE trial
dc.typeartículo
dc.volumen30
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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