dc.contributor.author | Jones, RL | |
dc.contributor.author | Serrano, C | |
dc.contributor.author | von Mehren, M | |
dc.contributor.author | George, S | |
dc.contributor.author | Heinrich, MC | |
dc.contributor.author | Kang, Y-K | |
dc.contributor.author | Schöffski, P | |
dc.contributor.author | Cassier, PA | |
dc.contributor.author | Mir, O | |
dc.contributor.author | Chawla, SP | |
dc.contributor.author | Eskens, FALM | |
dc.contributor.author | Rutkowski, P | |
dc.contributor.author | Tap, WD | |
dc.contributor.author | Zhou, T | |
dc.contributor.author | Roche, M | |
dc.contributor.author | Bauer, S | |
dc.date.accessioned | 2021-05-25T11:53:26Z | |
dc.date.available | 2021-05-25T11:53:26Z | |
dc.identifier.citation | European journal of cancer (Oxford, England : 1990), 2021, 145 pp. 132 - 142 | |
dc.identifier.issn | 0959-8049 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4579 | |
dc.identifier.eissn | 1879-0852 | |
dc.identifier.doi | 10.1016/j.ejca.2020.12.008 | |
dc.description.abstract | Background 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.format | Print-Electronic | |
dc.format.extent | 132 - 142 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
dc.title | Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-12-08 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.ejca.2020.12.008 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | European journal of cancer (Oxford, England : 1990) | |
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.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.volume | 145 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Sarcoma Clinical Trials (R Jones) | |
icr.researchteam | Sarcoma Clinical Trials (R Jones) | en_US |
dc.contributor.icrauthor | Jones, Robin | |