Journal of Neuro-Oncology

, Volume 136, Issue 1, pp 115–125 | Cite as

Randomized phase II trial comparing axitinib with the combination of axitinib and lomustine in patients with recurrent glioblastoma

  • J. DuerinckEmail author
  • S. Du Four
  • F. Bouttens
  • C. Andre
  • V. Verschaeve
  • F. Van Fraeyenhove
  • C. Chaskis
  • N. D’Haene
  • M. Le Mercier
  • A. Rogiers
  • A. Michotte
  • I. Salmon
  • B. Neyns
Clinical Study


Axitinib is a small molecule tyrosine kinase inhibitor with high affinity and specificity for the family of vascular endothelial growth factor receptors. It has previously demonstrated anti-tumor activity in a small cohort of patients with recurrent glioblastoma (rGB). We conducted a non-comparative randomized phase II clinical trial investigating axitinib monotherapy versus axitinib plus lomustine (LOM) in patients with rGB. Primary endpoint was 6 month progression-free survival (6mPFS). Patients who progressed on axitinib-monotherapy were allowed to cross-over. Between August 2011 and July 2015, 79 patients were randomized and initiated axitinib monotherapy (n = 50; AXI) or axitinib plus lomustine (n = 29; AXILOM). Median age was 55y [range 18–80], 50M/28F. Baseline characteristics were well balanced between study arms. Nineteen patients in the AXI-arm crossed-over at the time of progression. Treatment was generally well tolerated. AXILOM patients were at higher risk for grade 3/4 neutropenia (0 vs. 21%) and thrombocytopenia (4 vs. 29%). Best Overall Response Rate (BORR) in the AXI-arm was 28 vs. 38% in the AXILOM-arm. 6mPFS was 26% (95% CI 14–38) versus 17% (95% CI 2–32) for patients treated in the AXI versus AXILOM-arms, respectively. Median overall survival was 29 weeks (95% CI 20–38) in the AXI-arm and 27.4 weeks (95% CI 18.4–36.5) in the AXILOM-arm. MGMT-promoter hypermethylation and steroid treatment at baseline correlated significantly with PFS and OS. We conclude from these results that axitinib improves response rate and progression-free survival in patients with rGB compared to historical controls. There is no indication that upfront combination of axitinib with LOM improves results (European Clinical Trials Database (EudraCT) Study Number: 2011-000900-16).


Glioblastoma Recurrent Axitinib Lomustine 



We would like to acknowledge the patients who consented to participate in this study, their families and professional health care providers. Pfizer Belgium for the provision of axitinib study medication and a research grant. We would also like to thank the data manager Katrien Van den Bossche and Kathleen Mooren (UZ Brussel) for their help with the data collection and analysis, and Ludwig Van den Hove, PhD (Pfizer Belgium), for his support and critical review of the manuscript.

Supplementary material

11060_2017_2629_MOESM1_ESM.docx (21 kb)
Supplementary material 1 (DOCX 21 KB)


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • J. Duerinck
    • 1
    Email author
  • S. Du Four
    • 1
  • F. Bouttens
    • 2
  • C. Andre
    • 3
  • V. Verschaeve
    • 4
  • F. Van Fraeyenhove
    • 5
  • C. Chaskis
    • 6
  • N. D’Haene
    • 7
  • M. Le Mercier
    • 7
  • A. Rogiers
    • 8
  • A. Michotte
    • 9
  • I. Salmon
    • 7
  • B. Neyns
    • 10
  1. 1.Department of NeurosurgeryUniversitair Ziekenhuis BrusselBrusselsBelgium
  2. 2.Department of Medical and Radiation OncologyAZ Sint-Lucas GentGhentBelgium
  3. 3.Department of Medical OncologyCHU LiègeLiègeBelgium
  4. 4.Department of Medical OncologyGHDCCharleroiBelgium
  5. 5.Department of Medical OncologyZNA MiddelheimAntwerpBelgium
  6. 6.Department of NeurosurgeryCHU CharleroiCharleroiBelgium
  7. 7.Department of PathologyHopital Erasme Université Libre de BruxellesBrusselsBelgium
  8. 8.Department of PsychiatryCHU BrugmannBrusselsBelgium
  9. 9.Departments of Pathology and NeurologyUniversitair Ziekenhuis BrusselBrusselsBelgium
  10. 10.Department of Medical OncologyUniversitair Ziekenhuis BrusselBrusselsBelgium

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