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Phase II study of Dovitinib in recurrent glioblastoma

  • Mayur Sharma
  • Cathy Schilero
  • David M. Peereboom
  • Brian P. Hobbs
  • Paul Elson
  • Glen H. J. Stevens
  • Keith McCrae
  • Andrew B. Nixon
  • Manmeet S. AhluwaliaEmail author
Clinical Study

Abstract

Introduction

Dovitinib is an oral, potent inhibitor of FGFR and VEGFR, and can be a promising strategy in patients with recurrent or progressive glioblastoma (GBM).

Methods

This was an open label phase II study of two arms: Arm 1 included anti-angiogenic naïve patients with recurrent GBM and Arm 2 included patients with recurrent GBM that had progressed on prior anti-angiogenic therapy. Nineteen subjects were enrolled in Arm 1 and 14 subjects in Arm 2. The primary endpoint was 6-month progression-free survival (PFS-6) in Arm 1 and time to progression (TTP) in Arm 2. The secondary endpoints were toxicity, objective response rate (ORR) and overall survival.

Results

Patients in Arm 2 (compared to Arm 1) tended to have longer intervals from diagnosis to study entry (median 26.9 vs. 8.9 months, p = 0.002), experienced more recurrences (64%, had 3–4 prior recurrences compared to 0, p < 0.0001) and tended to be heavily pretreated (71% vs. 26–32% p = 0.04 or 0.02). 6-month PFS was 12% ± 6% for the Arm 1 and 0% for Arm 2. TTP was similar in both treatment arms (median 1.8 months Arm 1 and 0.7–1.8 months Arm 2, p = 0.36). Five patients (15%) had grade 4 toxicities and 22 patients (67%) had grade 3 toxicities. There were no significant differences between the two arms with respect to the amount of change in the levels of biomarkers from baseline.

Conclusion

Dovitinib was not efficacious in prolonging the PFS in patients with recurrent GBM irrespective of prior treatment with anti-angiogenic therapy (including bevacizumab).

Keywords

Dovitinib Glioblastoma Recurrent Bevacizumab Anti-angiogenic therapy 

Notes

Funding

This study was supported by Novartis.

Compliance with ethical standards

Conflicts of interest

Dr. Ahluwalia’s disclosures are: receipt of grants/research supports: Astrazeneca, Abbvie, BMS, Bayer, Incyte, Pharmacyclics, Novocure, Merck. Receipt of honoraria or consultation fees: Elsevier, Wiley, Astrazeneca, Abvvie, VBI Vaccines, Flatiron, Varian Medical Systems, Prime Education, Bayer; Stock shareholder: Doctible, Mimivax. There are no potential conflicts of interest for other authors.

Supplementary material

11060_2019_3236_MOESM1_ESM.docx (15 kb)
Supplementary file1 (DOCX 14 kb)
11060_2019_3236_MOESM2_ESM.docx (17 kb)
Supplementary file2 (DOCX 17 kb)
11060_2019_3236_MOESM3_ESM.jpg (385 kb)
Supplementary file3 (JPG 385 kb). Correlation between biomarkers and progression free survival (PFS) a) BMP 9 [<27.0 (blue) vs >27.0 (red)] b) Baseline Endoglin [<250.0 (blue) vs > 250.0 (red)] c) Baseline CD73 [<1.2 (blue) vs >1.2 (red)] d) Baseline TSP 2 [<1800 (blue) vs >1800 (red)] e) Overall Change in TGFβ 2 at Cycle 1 Day 28 f) Overall Change in VEGF R3 at Cycle 1 Day 28. (Blue (-1) =decrease compared to baseline; red (1) =increase)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Mayur Sharma
    • 1
  • Cathy Schilero
    • 1
  • David M. Peereboom
    • 1
    • 2
  • Brian P. Hobbs
    • 3
  • Paul Elson
    • 3
  • Glen H. J. Stevens
    • 1
    • 2
  • Keith McCrae
    • 2
  • Andrew B. Nixon
    • 4
  • Manmeet S. Ahluwalia
    • 1
    • 2
    Email author
  1. 1.Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological InstituteCleveland ClinicClevelandUSA
  2. 2.Taussig Cancer InstituteCleveland ClinicClevelandUSA
  3. 3.Quantitative Health SciencesCleveland ClinicClevelandUSA
  4. 4.Duke Cancer InstituteDuke University Medical CenterDurhamUSA

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