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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorJones, Robin L.
dc.contributor.authorSerrano Garcia, César
dc.contributor.authorvon Mehren, Margaret
dc.contributor.authorGeorge, Suzanne
dc.contributor.authorHeinrich, Michael C.
dc.contributor.authorKang, Yoon-Koo
dc.date.accessioned2021-07-05T08:27:28Z
dc.date.available2021-07-05T08:27:28Z
dc.date.issued2021-03
dc.identifier.citationJones 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.issn0959-8049
dc.identifier.urihttp://hdl.handle.net/11351/6119
dc.descriptionAvapritinib; Gastrointestinal stromal tumours; PDGFRA
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.language.isoeng
dc.publisherElsevier
dc.relation.ispartofseriesEuropean Journal of Cancer;145
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceScientia
dc.subjectMutació (Biologia)
dc.subjectInhibidors enzimàtics - Ús terapèutic - Eficàcia
dc.subjectAparell digestiu - Càncer
dc.subject.meshGastrointestinal Stromal Tumors
dc.subject.mesh/drug therapy
dc.subject.meshMutation
dc.subject.meshTreatment Outcome
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.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1016/j.ejca.2020.12.008
dc.subject.decstumores del estroma gastrointestinal
dc.subject.decs/farmacoterapia
dc.subject.decsmutación
dc.subject.decsresultado del tratamiento
dc.relation.publishversionhttps://linkinghub.elsevier.com/retrieve/pii/S0959804920314234
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[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.identifier.pmid33465704
dc.identifier.wos000625301200013
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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