Imatinib in combination with phosphoinositol kinase inhibitor buparlisib in patients with gastrointestinal stromal tumour who failed prior therapy with imatinib and sunitinib: a Phase 1b, multicentre study.

Autor: Gelderblom H; Leiden University Medical Center, Leiden, The Netherlands. a.j.gelderblom@lumc.nl., Jones RL; The Royal Marsden Hospital and Institute of Cancer Research, London, UK., George S; Dana-Farber Cancer Institute Boston, Boston, MA, USA., Valverde Morales C; Vall D'Hebron University Hospital, Barcelona, Spain., Benson C; The Royal Marsden Hospital, London, UK., Jean-Yves Blay; Centre Léon Bérard, Lyon, France.; Unicancer, Paris, France., Renouf DJ; BC Cancer - Vancouver Centre, Vancouver, Canada., Doi T; National Cancer Center Hospital East, Kashiwa, Japan., Le Cesne A; Institut Gustave Roussy, Villejuif Cedex, France., Leahy M; The Christie Hospital, Manchester, UK., Hertle S; Novartis Pharma AG, Basel, Switzerland., Aimone P; Novartis Pharma AG, Basel, Switzerland., Brandt U; Novartis Pharma AG, Basel, Switzerland., Schӧffski P; University Hospitals Leuven, Department of General Medical Oncology, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2020 Apr; Vol. 122 (8), pp. 1158-1165. Date of Electronic Publication: 2020 Mar 09.
DOI: 10.1038/s41416-020-0769-y
Abstrakt: Background: The majority of patients with advanced gastrointestinal stromal tumours (GISTs) develop resistance to imatinib and sunitinib, the standard of care for these patients. This study evaluated the combination of buparlisib, an oral phosphoinositide 3-kinase (PI3K) inhibitor, with imatinib in patients with advanced GIST, who have failed prior therapy with imatinib and sunitinib.
Methods: This Phase 1b, multicentre, open-label study aimed to determine the maximum tolerated dose (MTD) and/or a recommended Phase 2 dose of buparlisib in combination with 400 mg of imatinib through a dose-escalation part and a dose-expansion part, and also evaluated the clinical profile of the combination.
Results: Sixty patients were enrolled, including 25 in the dose-escalation part and 35 in the dose-expansion part. In the combination, MTD of buparlisib was established as 80 mg. No partial or complete responses were observed. The estimated median progression-free survival was 3.5 months in the expansion phase. Overall, 98.3% of patients had treatment-related adverse events (AEs), including 45% with grade 3 or 4 AEs.
Conclusions: Buparlisib in combination with imatinib provided no additional benefit compared with currently available therapies. Due to the lack of objective responses, further development of this combination was not pursued for third-line/fourth-line advanced/metastatic GIST.
Trial Registration Number: NCT01468688.
Databáze: MEDLINE
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