dc.contributor
Institut Català de la Salut
dc.contributor
[Jones RL] Royal Marsden Hospital and Institute of Cancer Research, London, UK. [Serrano C] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [von Mehren M] Fox Chase Cancer Center, Philadelphia, PA, USA. [George S] Dana-Farber Cancer Institute, Boston, MA, USA. [Heinrich MC] Portland VA Health Care System and OHSU Knight Cancer Institute, Portland, OR, USA. [Kang YK] Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Jones, Robin L.
dc.contributor.author
Serrano Garcia, César
dc.contributor.author
von Mehren, Margaret
dc.contributor.author
Heinrich, Michael C.
dc.contributor.author
Kang, Yoon-Koo
dc.contributor.author
George, Suzanne
dc.date.accessioned
2025-10-25T05:37:42Z
dc.date.available
2025-10-25T05:37:42Z
dc.date.issued
2021-07-05T08:27:28Z
dc.date.issued
2021-07-05T08:27:28Z
dc.identifier
Jones RL, Serrano C, von Mehren M, George S, Heinrich MC, Kang YK, et al. Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial. Eur J Cancer. 2021 Mar;145:132-142.
dc.identifier
https://hdl.handle.net/11351/6119
dc.identifier
10.1016/j.ejca.2020.12.008
dc.identifier
000625301200013
dc.identifier.uri
http://hdl.handle.net/11351/6119
dc.description.abstract
Avapritinib; Tumors de l'estroma gastrointestinal; PDGFRA
dc.description.abstract
Avapritinib; Tumores del estroma gastrointestinal; PDGFRA
dc.description.abstract
Avapritinib; Gastrointestinal stromal tumours; PDGFRA
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.description.abstract
The NAVIGATOR study (NCT02508532) was supported by Blueprint Medicines Corporation, Cambridge, Massachusetts, USA.
dc.format
application/pdf
dc.format
application/pdf
dc.format
application/pdf
dc.relation
European Journal of Cancer;145
dc.relation
https://linkinghub.elsevier.com/retrieve/pii/S0959804920314234
dc.rights
Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Mutació (Biologia)
dc.subject
Inhibidors enzimàtics - Ús terapèutic - Eficàcia
dc.subject
Aparell digestiu - Càncer
dc.subject
DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Neoplasms, Connective Tissue::Gastrointestinal Stromal Tumors
dc.subject
Other subheadings::Other subheadings::Other subheadings::/drug therapy
dc.subject
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome
dc.subject
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de tejido conjuntivo y de tejidos blandos::neoplasias de tejido conjuntivo::tumores del estroma gastrointestinal
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
dc.subject
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento
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
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
