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Journal of Neuro-Oncology

, Volume 126, Issue 1, pp 185–192 | Cite as

A phase II study of bevacizumab and erlotinib after radiation and temozolomide in MGMT unmethylated GBM patients

  • J. J. Raizer
  • P. Giglio
  • J. Hu
  • M. Groves
  • R. Merrell
  • C. Conrad
  • S. Phuphanich
  • V. K. Puduvalli
  • M. Loghin
  • N. Paleologos
  • Y. Yuan
  • D. Liu
  • A. Rademaker
  • W. K. Yung
  • B. Vaillant
  • J. Rudnick
  • M. Chamberlain
  • N. Vick
  • S. Grimm
  • I. W. Tremont-Lukats
  • J. De Groot
  • K. Aldape
  • M. R. Gilbert
  • Brain Tumor Trials Collaborative
Clinical Study

Abstract

Survival for glioblastoma (GBM) patients with an unmethyated MGMT promoter in their tumor is generally worse than methylated MGMT tumors, as temozolomide (TMZ) response is limited. How to better treat patients with unmethylated MGMT is unknown. We performed a trial combining erlotinib and bevacizumab in unmethylated GBM patients after completion of radiation (RT) and TMZ. GBM patients with an unmethylated MGMT promoter were trial eligible. Patient received standard RT (60 Gy) and TMZ (75 mg/m2 × 6 weeks) after surgical resection of their tumor. After completion of RT they started erlotinib 150 mg daily and bevacizumab 10 mg/kg every 2 weeks until progression. Imaging evaluations occurred every 8 weeks. The primary endpoint was overall survival. Of the 48 unmethylated patients enrolled, 46 were evaluable (29 men and 17 women); median age was 55.5 years (29–75) and median KPS was 90 (70–100). All patients completed RT with TMZ. The median number of cycles (1 cycle was 4 weeks) was 8 (2–47). Forty-one patients either progressed or died with a median progression free survival of 9.2 months. At a follow up of 33 months the median overall survival was 13.2 months. There were no unexpected toxicities and most observed toxicities were categorized as CTC grade 1 or 2. The combination of erlotinib and bevacizumab is tolerable but did not meet our primary endpoint of increasing survival. Importantly, more trials are needed to find better therapies for GBM patients with an unmethylated MGMT promoter.

Keywords

MGMT Glioblastoma Erlotinib Bevacizumab 

Notes

Author contributions

Statistical Analysis was performed by (YY, DL and AR), Drafting/revising the manuscript-all authors. Study concept or design-JJR, AR, YY, MG. Analysis or interpretation of data-JJR, YY, DL, MG. Statistical Analysis was performed by (YY, DL and AR)

Compliance with ethical standards

Conflict of interest

JJR-Research Support: Genentech, Novartis, Plexxikon, Celldex, Diffusion, Stemline; Advisory Board: Stemline, Novocure, Midatech, AbbVie, Proximagen; Speakers Bureau: Genentech. MG-Research Support: GSK. Speakers Bureau: Foundation Medicine; Advisory Board: Incyte, Genentech, Foundation Medicine. VKP-Advisory board and honoraria: Nektar therapeutics, Orbus Pharma, Celgene, Genentech, Foundation Medicine; Speaker: Depuy Synthes. AY-Consultant: Merck, Actelion, DNAtrix; Honoraria: Merck, Actalion; Research Fund, None. JR-Advisory Board: Novocure. SG-Advisory Board: AbbVie and Novocure, JD-Advisory Board: Genentech, Novartis, Celldex, Foundation Medicine, Celldex, Deciphera Pharmaceuticals. Research Support: Sanofi-Aventis, AstraZeneca, EMD-Serono, Eli Lilly, Novartis, Deciphera Pharmaceuticals. PG, JH, RM, CC, SP, ML, NP, YY, DL, AR, BV, MC, NV, IWT-L, KA, MRG—none.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • J. J. Raizer
    • 1
  • P. Giglio
    • 2
  • J. Hu
    • 3
  • M. Groves
    • 4
  • R. Merrell
    • 5
  • C. Conrad
    • 4
  • S. Phuphanich
    • 3
  • V. K. Puduvalli
    • 2
  • M. Loghin
    • 6
  • N. Paleologos
    • 7
  • Y. Yuan
    • 8
  • D. Liu
    • 8
  • A. Rademaker
    • 9
  • W. K. Yung
    • 6
  • B. Vaillant
    • 10
  • J. Rudnick
    • 3
  • M. Chamberlain
    • 11
  • N. Vick
    • 5
  • S. Grimm
    • 1
  • I. W. Tremont-Lukats
    • 6
  • J. De Groot
    • 6
  • K. Aldape
    • 12
  • M. R. Gilbert
    • 13
  • Brain Tumor Trials Collaborative
  1. 1.Department of NeurologyNorthwestern UniversityChicagoUSA
  2. 2.James Cancer HospitalOhio State UniversityColumbusUSA
  3. 3.Departments of Neurology and NeurosurgeryCedars-Sinai Medical CenterLos AngelesUSA
  4. 4.Austin Brain Tumor CenterAustinUSA
  5. 5.Department of NeurologyNorthShore University Health SystemEvanstonUSA
  6. 6.Department of Neuro-OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  7. 7.Department of NeurologyRush University Medical CenterChicagoUSA
  8. 8.Department of BiostatisticsUniversity of Texas MD Anderson Cancer CenterHoustonUSA
  9. 9.Department of Preventive MedicineNorthwestern UniversityChicagoUSA
  10. 10.Dell Medical SchoolThe University of TexasAustinUSA
  11. 11.Department of NeurologyUniversity of WashingtonSeattleUSA
  12. 12.Department of PathologyPrincess Margaret Cancer CentreTorontoCanada
  13. 13.Neuro-Oncology BranchNIHBethesdaUSA

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