dc.contributor.author | Bauer, S | |
dc.contributor.author | Heinrich, MC | |
dc.contributor.author | George, S | |
dc.contributor.author | Zalcberg, JR | |
dc.contributor.author | Serrano, C | |
dc.contributor.author | Gelderblom, H | |
dc.contributor.author | Jones, RL | |
dc.contributor.author | Attia, S | |
dc.contributor.author | D'Amato, G | |
dc.contributor.author | Chi, P | |
dc.contributor.author | Reichardt, P | |
dc.contributor.author | Meade, J | |
dc.contributor.author | Su, Y | |
dc.contributor.author | Ruiz-Soto, R | |
dc.contributor.author | Blay, J-Y | |
dc.contributor.author | von Mehren, M | |
dc.contributor.author | Schöffski, P | |
dc.date.accessioned | 2021-12-07T14:50:58Z | |
dc.date.available | 2021-12-07T14:50:58Z | |
dc.date.issued | 2021-09-09 | |
dc.identifier.citation | Clinical cancer research : an official journal of the American Association for Cancer Research, 2021 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4914 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.ccr-21-1864 | |
dc.description.abstract | Purpose Most patients with gastrointestinal stromal tumor (GIST) have activating mutations in KIT/PDGFRA and are initially responsive to tyrosine kinase inhibitors (TKIs). The acquisition of secondary mutations leads to refractory/relapsed disease. This study reports the results of an analysis from the phase 3 INVICTUS study (NCT03353753) characterizing the genomic heterogeneity of tumors from patients with advanced GIST and evaluating ripretinib efficacy across KIT/PDGFRA mutation subgroups. Patients and methods Tumor tissue and liquid biopsy samples that captured circulating tumor DNA were collected prior to study enrollment and sequenced using next-generation sequencing. Subgroups were determined by KIT/PDGFRA mutations and correlation of clinical outcomes and KIT/PDGFRA mutational status was assessed. Results Overall, 129 patients enrolled (ripretinib 150 mg once daily, n=85; placebo, n=44). The most common primary mutation subgroup detected by combined tissue and liquid biopsies were in KIT exon 11 (ripretinib, 61.2%; placebo, 77.3%) and KIT exon 9 (ripretinib, 18.8%; placebo, 15.9%). Patients receiving ripretinib demonstrated progression-free survival (PFS) benefit vs placebo regardless of mutation status (hazard ratio 0.16) and in all assessed subgroups in Kaplan-Meier PFS analysis (exon 11, P <0.0001; exon 9, P =0.0023; exon 13, P <0.0001; exon 17, P <0.0001). Among patients with wild-type KIT/PDGFRA by tumor tissue, PFS ranged from 2-23 months for ripretinib vs 0.9-10.1 months for placebo Conclusions: Ripretinib provided clinically meaningful activity across mutation subgroups in patients with advanced GIST, demonstrating ripretinib inhibits a broad range of KIT/PDGFRA mutations in patients with advanced GIST who were previously treated with 3 or more TKIs. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
dc.title | Clinical activity of ripretinib in patients with advanced gastrointestinal stromal tumor harboring heterogenous KIT/PDGFRA mutations in the phase 3 INVICTUS study. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-09-07 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1158/1078-0432.ccr-21-1864 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.licenseref.startdate | 2021-09-09 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Clinical cancer research : an official journal of the American Association for Cancer Research | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials (R Jones) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials (R Jones)/Sarcoma Clinical Trials (R Jones) (hon.) | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.embargo.terms | Not known | |
icr.researchteam | Sarcoma Clinical Trials (R Jones) | |
dc.contributor.icrauthor | Jones, Robin | |