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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)

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

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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Acknowledgements

The authors would like to thank participating patients, their families, and site personnel for their very important contributions to this clinical trial.

Funding

Novartis Pharmaceuticals providing funding for this study and the study drug, BKM120.

Author information

Authors and Affiliations

  1. Tennessee Oncology PLLC, 4220 Harding Road, Ste. 200, Nashville, TN, 37205, USA

    John D. Hainsworth

  2. Yale University, New Haven, CT, USA

    Kevin P. Becker

  3. Florida Cancer Specialists/SCRI, Ft. Myers, FL, USA

    Tarek Mekhail, Sajeel A. Chowdhary, Janice Faulkner Eakle & David Wright

  4. Nebraska Methodist Cancer Center, Omaha, NE, USA

    Robert M. Langdon

  5. Grand Rapids Oncology Program, Grand Rapids, MI, USA

    Kathleen J. Yost & Gilbert Darin Anthony Padula

  6. Sarah Cannon, Nashville, TN, USA

    Kimberly West-Osterfield, Meredith Scarberry, Candice A. Shaifer & Mythili Shastry

  7. Sarah Cannon Research Institute/Tennessee Oncology PLLC, Nashville, TN, USA

    Howard A. Burris III & Kent Shih

Authors
  1. John D. Hainsworth
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  2. Kevin P. Becker
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Correspondence to Kent Shih.

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Hainsworth, J.D., Becker, K.P., Mekhail, T. et al. 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). J Neurooncol 144, 303–311 (2019). https://doi.org/10.1007/s11060-019-03227-7

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  • DOI: https://doi.org/10.1007/s11060-019-03227-7

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