dc.contributor
Institut Català de la Salut
dc.contributor
[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.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Pantaleo, Maria Abbondanza
dc.contributor.author
Heinrich, Michael C.
dc.contributor.author
Valverde Morales, Claudia Maria
dc.contributor.author
Schöfski, Patrick
dc.contributor.author
Grignani, Giovanni
dc.contributor.author
Italiano, Antoine
dc.date.accessioned
2025-10-24T10:40:35Z
dc.date.available
2025-10-24T10:40:35Z
dc.date.issued
2022-09-12T10:10:45Z
dc.date.issued
2022-09-12T10:10:45Z
dc.date.issued
2022-05-06
dc.identifier
Pantaleo 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
https://hdl.handle.net/11351/8159
dc.identifier
10.1186/s12885-022-09610-4
dc.identifier
000791786100010
dc.identifier.uri
https://hdl.handle.net/11351/8159
dc.description.abstract
Alpelisib; Gastrointestinal stromal tumor; Imatinib
dc.description.abstract
Alpelisib; Tumor estromal gastrointestinal; Imatinib
dc.description.abstract
Alpelisib; Tumor estromal gastrointestinal; Imatinib
dc.description.abstract
Background
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.description.abstract
The study was funded by the Novartis Pharma AG, Basel, Switzerland.
dc.format
application/pdf
dc.relation
BMC Cancer;22
dc.relation
https://doi.org/10.1186/s12885-022-09610-4
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Aparell digestiu - Càncer - Tractament
dc.subject
Avaluació de resultats (Assistència sanitària)
dc.subject
DISEASES::Digestive System Diseases::Digestive System Neoplasms::Gastrointestinal Neoplasms::Digestive System Diseases::Gastrointestinal Stromal Tumors
dc.subject
Other subheadings::Other subheadings::Other subheadings::/drug therapy
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome
dc.subject
ENFERMEDADES::enfermedades del sistema digestivo::neoplasias del sistema digestivo::neoplasias gastrointestinales::enfermedades del sistema digestivo::tumores del estroma gastrointestinal
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento
dc.title
A multicenter, dose-finding, phase 1b study of imatinib in combination with alpelisib as third-line treatment in patients with advanced gastrointestinal stromal tumor
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
