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Title: Buparlisib plus carboplatin or lomustine in patients with recurrent glioblastoma: a phase Ib/II, open-label, multicentre, randomised study.
Austin Authors: Rosenthal, Mark;Clement, Paul M;Campone, Mario;Gil-Gil, Miguel J;DeGroot, John;Chinot, Olivier;Idbaih, Ahmed;Gan, Hui K ;Raizer, Jeffrey;Wen, Patrick Yung;Pineda, Estela;Donnet, Valerie;Mills, David;El-Hashimy, Mona;Mason, Warren
Affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA
Department of Oncology, Leuven Cancer Institute, Leuven, Belgium
Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Institut Català d'Oncologia, Barcelona, Spain
Department of Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Department of Neuro-Oncology, Northwestern Medical Faculty Foundation, Chicago, Illinois, USA
Medical Oncology, University of Barcelona Faculty of Medicine and Health Sciences, Barcelona, Catalunya, Spain
Medical Oncology
Medical Oncology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
Institut de Cancérologie de l'Ouest, Centre René Gauducheau, Saint Herblain, Pays de la Loire, France
Department of Neuro-Oncology, Assistance Publique - Hôpitaux de Marseille Office Central des Bibliothèques, Marseille, Provence-Alpes-Côte d'Azur, France
Department of Neuro-Oncology, Sorbonne Université, Paris, Île-de-France, France
Novartis Pharma SAS, Paris, France
Novartis Pharma, Basel, Basel-Stadt, Switzerland
Department of Oncology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada
Olivia Newton-John Cancer Wellness and Research Centre
Issue Date: Jul-2020
Date: 2020-07
Publication information: ESMO Open 2020; 5(4); e000672
Abstract: Glioblastoma relapse is associated with activation of phosphatidylinositol 3-kinase (PI3K) signalling pathway. In preclinical studies, the pan-PI3K inhibitor buparlisib showed antitumour activity in glioma models. This was a two-part, multicentre, phase Ib/II study in patients with recurrent glioblastoma pretreated with radiotherapy and temozolomide standard of care. Patients received buparlisib (80 mg or 100 mg once daily) plus carboplatin (area under the curve (AUC)=5 every 3 weeks), or buparlisib (60 mg once daily) plus lomustine (100 mg/m2 every 6 weeks). The primary endpoint was to determine the maximum tolerable dose (MTD) and/or recommended phase II dose of buparlisib plus carboplatin or lomustine. Between 28 February 2014 and 7 July 2016, 35 patients were enrolled and treated with buparlisib plus carboplatin (n=17; buparlisib (80 mg) plus carboplatin, n=3; and buparlisib (100 mg) plus carboplatin, n=14), or buparlisib (60 mg) plus lomustine (n=18). The MTD of buparlisib was determined to be 100 mg per day in combination with carboplatin at an AUC of 5 every 3 weeks. The MTD of buparlisib in combination with lomustine could not be determined as it did not satisfy the MTD criteria per the Bayesian logistic regression model. The overall safety profile of buparlisib remained unchanged, and no new or unexpected safety findings were reported in this study. Preliminary assessment for both combinations did not demonstrate sufficient antitumour activity compared with historical data on single-agent carboplatin or lomustine. NCT01934361.
DOI: 10.1136/esmoopen-2020-000672
ORCID: 0000-0003-1152-6764
Journal: ESMO Open
PubMed URL: 32665311
Type: Journal Article
Subjects: BKM120
recurrent glioblastoma
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