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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorPantaleo, Maria Abbondanza
dc.contributor.authorHeinrich, Michael C.
dc.contributor.authorItaliano, Antoine
dc.contributor.authorValverde Morales, Claudia Maria
dc.contributor.authorSchöfski, Patrick
dc.contributor.authorGrignani, Giovanni
dc.date.accessioned2022-09-12T10:10:45Z
dc.date.available2022-09-12T10:10:45Z
dc.date.issued2022-05-06
dc.identifier.citationPantaleo MA, Heinrich MC, Italiano A, Valverde C, Schöffski P, Grignani G, et al. A multicenter, dose-finding, phase 1b study of imatinib in combination with alpelisib as third-line treatment in patients with advanced gastrointestinal stromal tumor. BMC Cancer. 2022 May 6;22:511.
dc.identifier.issn1471-2407
dc.identifier.urihttp://hdl.handle.net/11351/8159
dc.descriptionAlpelisib; Gastrointestinal stromal tumor; Imatinib
dc.description.abstractBackground Acquired resistance to approved tyrosine kinase inhibitors limits their clinical use in patients with gastrointestinal stromal tumor (GIST). This study investigated the safety, tolerability and efficacy of alpelisib, a phosphatidylinositol 3-kinase inhibitor, used in combination with imatinib in patients with advanced GIST who had failed prior therapy with both imatinib and sunitinib. Methods This phase 1b, multicenter, open-label study consisted of 2 phases: dose escalation and dose expansion. Dose escalation involved 200 mg once daily (QD) alpelisib, initially, followed by 250 and 350 mg. These were combined with 400 mg QD imatinib until maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) of alpelisib in combination with imatinib was determined. This MTD/RP2D dose was tested to evaluate the clinical activity of this combination in dose expansion. Results Fifty-six patients were enrolled, 21 and 35 in the dose escalation and expansion phases, respectively. The MTD of alpelisib given with imatinib was determined as 350 mg QD. Combination treatment showed partial response in 1 (2.9%) and stable disease in 15 (42.9%) patients. Median progression-free survival was 2 months (95% CI 1.8–4.6). Overall, 92.9% patients had adverse events (AEs) while 46.4% had grade 3/4 AEs, hyperglycemia being the most common (23.2%). Conclusions The MTD of alpelisib was estimated as 350 mg QD when used in combination with imatinib 400 mg QD after oral administration in patients with advanced GIST. The safety and tolerability profile of this combination was acceptable; however, the combination did not demonstrate sufficient clinical activity to justify additional clinical testing.
dc.language.isoeng
dc.publisherBMC
dc.relation.ispartofseriesBMC Cancer;22
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectAparell digestiu - Càncer - Tractament
dc.subjectAvaluació de resultats (Assistència sanitària)
dc.subject.meshGastrointestinal Stromal Tumors
dc.subject.mesh/drug therapy
dc.subject.meshTreatment Outcome
dc.titleA multicenter, dose-finding, phase 1b study of imatinib in combination with alpelisib as third-line treatment in patients with advanced gastrointestinal stromal tumor
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1186/s12885-022-09610-4
dc.subject.decstumores del estroma gastrointestinal
dc.subject.decs/farmacoterapia
dc.subject.decsresultado del tratamiento
dc.relation.publishversionhttps://doi.org/10.1186/s12885-022-09610-4
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Pantaleo MA] Division in Medical Oncology, IRCSS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. [Heinrich MC] Portland VA Health Care System and Oregon Health and Science University, Knight Cancer Institute, Portland, Oregon, USA. [Italiano A] Institut Bergonie, Bordeaux, France. [Valverde C] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Schöffski P] Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, and Laboratory of Experimental Oncology, KU Leuven, Leuven, Belgium. [Grignani G] Division of Medical Oncology, Candiolo Cancer Institute, TO, Italy
dc.identifier.pmid35524239
dc.identifier.wos000791786100010
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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