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01-09-2019 | Glioblastoma | Clinical Study

Phase I/II study of bevacizumab with BKM120, an oral PI3K inhibitor, in patients with refractory solid tumors (phase I) and relapsed/refractory glioblastoma (phase II)

Authors: John D. Hainsworth, Kevin P. Becker, Tarek Mekhail, Sajeel A. Chowdhary, Janice Faulkner Eakle, David Wright, Robert M. Langdon, Kathleen J. Yost, Gilbert Darin Anthony Padula, Kimberly West-Osterfield, Meredith Scarberry, Candice A. Shaifer, Mythili Shastry, Howard A. Burris III, Kent Shih

Published in: Journal of Neuro-Oncology | Issue 2/2019

Abstract

Background

Current bevacizumab-based regimens have failed to improve survival in patients with recurrent glioblastoma. To improve treatment efficacy, we evaluated bevacizumab + BKM120, an oral pan-class I PI3K inhibitor, in this patient population.

Methods

A brief phase I study established the optimal BKM120 dose to administer with standard-dose bevacizumab. BKM120 60 mg PO daily + bevacizumab 10 mg/kg IV every 2 weeks in 28-day cycles was then administered to patients with relapsed/refractory glioblastoma in the phase II portion.

Results

Eighty-eight patients enrolled (phase I, 12; phase II, 76). In phase I, BKM120 80 mg PO daily produced dose limiting toxicity in 3 of 6 patients; a BKM120 dose of 60 mg PO daily was established as the maximum tolerated dose. In phase II, the median progression-free survival (PFS) was 4.0 months (95% CI 3.4, 5.4), PFS at 6 months was 36.5%, and the overall response rate was 26%. Forty-two patients (57%) experienced one or more serious treatment related toxicities. The most common CNS toxicities included mood alteration (17%) and confusion (12%); however, these were often difficult to classify as treatment- versus tumor-related.

Conclusions

The efficacy seen in this study is similar to the efficacy previously reported with single-agent bevacizumab. This regimen was poorly tolerated, despite the low daily dose of BKM120. Further development of this combination for the treatment of glioblastoma is not recommended.

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Title: Phase I/II study of bevacizumab with BKM120, an oral PI3K inhibitor, in patients with refractory solid tumors (phase I) and relapsed/refractory glioblastoma (phase II)
Authors: John D. Hainsworth
Kevin P. Becker
Tarek Mekhail
Sajeel A. Chowdhary
Janice Faulkner Eakle
David Wright
Robert M. Langdon
Kathleen J. Yost
Gilbert Darin Anthony Padula
Kimberly West-Osterfield
Meredith Scarberry
Candice A. Shaifer
Mythili Shastry
Howard A. Burris III
Kent Shih
Publication date: 01-09-2019
Publisher: Springer US
Keywords: Glioblastoma
Solid Tumor
Glioblastoma
Glioblastoma
Bevacizumab
Published in: Journal of Neuro-Oncology / Issue 2/2019
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-019-03227-7

At a glance: The STEP trials

Springer Medicine

Phase I/II study of bevacizumab with BKM120, an oral PI3K inhibitor, in patients with refractory solid tumors (phase I) and relapsed/refractory glioblastoma (phase II)

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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