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dc.contributor.authorJones, RL
dc.contributor.authorSerrano, C
dc.contributor.authorvon Mehren, M
dc.contributor.authorGeorge, S
dc.contributor.authorHeinrich, MC
dc.contributor.authorKang, Y-K
dc.contributor.authorSchöffski, P
dc.contributor.authorCassier, PA
dc.contributor.authorMir, O
dc.contributor.authorChawla, SP
dc.contributor.authorEskens, FALM
dc.contributor.authorRutkowski, P
dc.contributor.authorTap, WD
dc.contributor.authorZhou, T
dc.contributor.authorRoche, M
dc.contributor.authorBauer, S
dc.date.accessioned2021-05-25T11:53:26Z
dc.date.available2021-05-25T11:53:26Z
dc.identifier.citationEuropean journal of cancer (Oxford, England : 1990), 2021, 145 pp. 132 - 142
dc.identifier.issn0959-8049
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4579
dc.identifier.eissn1879-0852
dc.identifier.eissn1879-0852en_US
dc.identifier.doi10.1016/j.ejca.2020.12.008
dc.identifier.doi10.1016/j.ejca.2020.12.008en_US
dc.description.abstractBackground PDGFRA D842V mutations occur in 5-10% of gastrointestinal stromal tumours (GISTs), and previously approved tyrosine kinase inhibitors (TKIs) are inactive against this mutation. Consequently, patients have a poor prognosis. We present an updated analysis of avapritinib efficacy and long-term safety in this patient population.Methods NAVIGATOR (NCT02508532), a two-part, open-label, dose-escalation/dose-expansion phase I study, enrolled adult patients with unresectable GISTs. Patients with PDGFRA D842V-mutant GIST were a prespecified subgroup within the overall safety population, which included patients who received ≥1 avapritinib dose. Primary end-points were overall response rate (ORR) and avapritinib safety profile. Secondary end-points were clinical benefit rate (CBR), duration of response (DOR) and progression-free survival (PFS). Overall survival (OS) was an exploratory end-point.Results Between 7 October 2015 and 9 March 2020, 250 patients enrolled in the safety population; 56 patients were included in the PDGFRA D842V population, 11 were TKI-naïve. At data cut-off, median follow-up was 27.5 months. Safety profile was comparable between the overall safety and PDGFRA D842V populations. In the PDGFRA D842V population, the most frequent adverse events were nausea (38 [68%] patients) and diarrhoea (37 [66%]), and cognitive effects occurred in 32 (57%) patients. The ORR was 91% (51/56 patients). The CBR was 98% (55/56 patients). The median DOR was 27.6 months (95% confidence interval [CI]: 17.6-not reached [NR]); median PFS was 34.0 months (95% CI: 22.9-NR). Median OS was not reached.Conclusion Targeting PDGFRA D842V-mutant GIST with avapritinib resulted in an unprecedented, durable clinical benefit, with a manageable safety profile. Avapritinib should be considered as first-line therapy for these patients.
dc.formatPrint-Electronic
dc.format.extent132 - 142
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleAvapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial.
dc.typeJournal Article
dcterms.dateAccepted2020-12-08
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1016/j.ejca.2020.12.008
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEuropean journal of cancer (Oxford, England : 1990)
pubs.notesNot 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.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-statusPublished
pubs.volume145en_US
pubs.embargo.termsNot known
icr.researchteamSarcoma Clinical Trials (R Jones)
icr.researchteamSarcoma Clinical Trials (R Jones)en_US
dc.contributor.icrauthorJones, Robinen


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