Phase II study of PX-866 in recurrent glioblastoma
Marshall W Pitz, Elizabeth A Eisenhauer, Mary V MacNeil, Brian Thiessen, Jacob C Easaw, David R Macdonald, David D Eisenstat, Ankineedu S Kakumanu, Muhammad Salim, Haji Chalchal, Jeremy Squire, Ming Sound Tsao, Suzanne Kamel-Reid, Shantanu Banerji, Dongsheng Tu, Jean Powers, Diana F Hausman, Warren P Mason, Marshall W Pitz, Elizabeth A Eisenhauer, Mary V MacNeil, Brian Thiessen, Jacob C Easaw, David R Macdonald, David D Eisenstat, Ankineedu S Kakumanu, Muhammad Salim, Haji Chalchal, Jeremy Squire, Ming Sound Tsao, Suzanne Kamel-Reid, Shantanu Banerji, Dongsheng Tu, Jean Powers, Diana F Hausman, Warren P Mason
Abstract
Background: Glioblastoma (GBM) is the most aggressive malignancy of the central nervous system in adults. Increased activity of the phosphatidylinositol-3-OH kinase (PI3K) signal transduction pathway is common. We performed a phase II study using PX-866, an oral PI3K inhibitor, in participants with recurrent GBM.
Methods: Patients with histologically confirmed GBM at first recurrence were given oral PX-866 at a dose of 8 mg daily. An MRI and clinical exam were done every 8 weeks. Tissue was analyzed for potential predictive markers.
Results: Thirty-three participants (12 female) were enrolled. Median age was 56 years (range 35-78y). Eastern Cooperative Oncology Group performance status was 0-1 in 29 participants and 2 in the remainder. Median number of cycles was 1 (range 1-8). All participants have discontinued therapy: 27 for disease progression and 6 for toxicity (5 liver enzymes and 1 allergic reaction). Four participants had treatment-related serious adverse events (1 liver enzyme, 1 diarrhea, 2 venous thromboembolism). Other adverse effects included fatigue, diarrhea, nausea, vomiting, and lymphopenia. Twenty-four participants had a response of progression (73%), 1 had partial response (3%, and 8 (24%) had stable disease (median, 6.3 months; range, 3.1-16.8 months). Median 6-month progression-free survival was 17%. None of the associations between stable disease and PTEN, PIK3CA, PIK3R1, or EGFRvIII status were statistically significant.
Conclusions: PX-866 was relatively well tolerated. Overall response rate was low, and the study did not meet its primary endpoint; however, 21% of participants obtained durable stable disease. This study also failed to identify a statistically significant association between clinical outcome and relevant biomarkers in patients with available tissue.
Keywords: PI3K; clinical trial; glioblastoma.
© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Source: PubMed