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Phase II trials of erlotinib or gefitinib in patients with recurrent meningioma

  • Clinical Study - Patient Study
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Abstract

There are no established treatments for recurrent meningioma when surgical and radiation options are exhausted. The epidermal growth factor receptor (EGFR) is often over-expressed in meningiomas and may promote tumor growth. In open label, single arm phase II studies of the EGFR inhibitors gefitinib (NABTC 00-01) and erlotinib (NABTC 01-03) for recurrent malignant gliomas, we included exploratory subsets of recurrent meningioma patients. We have pooled the data and report the results here. Patients with recurrent histologically confirmed meningiomas with no more than 2 previous chemotherapy regimens were treated with gefitinib 500 mg/day or erlotinib 150 mg/day until tumor progression or unacceptable toxicity. Twenty-five eligible patients were enrolled with median age 57 years (range 29–81) and median Karnofsky performance status (KPS) score 90 (range 60–100). Sixteen patients (64%) received gefitinib and 9 (36%) erlotinib. Eight patients (32%) had benign tumors, 9 (36%) atypical, and 8 (32%) malignant. For benign tumors, the 6-month progression-free survival (PFS6) was 25%, 12-month PFS (PFS12) 13%, 6-month overall survival (OS6) 63%, and 12-month OS (OS12) 50%. For atypical and malignant tumors, PFS6 was 29%, PFS12 18%, OS6 71%, and OS12 65%. The PFS and OS were not significantly different by histology. There were no objective imaging responses, but 8 patients (32%) maintained stable disease. Although treatment was well-tolerated, neither gefitinib nor erlotinib appear to have significant activity against recurrent meningioma. The role of EGFR inhibitors in meningiomas is unclear. Evaluation of multi-targeted inhibitors and EGFR inhibitors in combination with other targeted molecular agents may be warranted.

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Acknowledgments

Grant Support: 5-U01CA62399-09 (J.J. Raizer, L.E. Abrey, A.B. Lassman and L.M. DeAngelis), NABTC # CA62399 and Member # CA62422, GCRC Grant # M01-RR00079 (S.M. Chang, K.R. Lamborn and M.D. Prados); CA62412, GCRC Grant # CA16672 (W.K.A. Yung and M.R. Gilbert); U01CA62407-08 (P.Y. Wen), U01CA62421–08, GCRC Grant # M01 RR03186 (M. Mehta and I.H. Robins); U01CA62405, GCRC Grant # M01-RR00056 (F. Lieberman); U01 CA62399, GCRC Grant # M01-RR0865 (T.F. Cloughesy).

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Authors and Affiliations

  1. Center for Neuro-Oncology, Dana-Farber Cancer Institute, 44 Binney St. SW430B, Boston, MA, 02115, USA

    Andrew D. Norden & Patrick Y. Wen

  2. Feinberg School of Medicine, Department of Neurology, Northwestern University, 710 N. Lake Shore Dr, Chicago, IL, 60611, USA

    Jeffrey J. Raizer

  3. Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY, 10021, USA

    Lauren E. Abrey, Andrew B. Lassman & Lisa M. DeAngelis

  4. Department of Neurological Surgery, University of California San Francisco, 400 Parnassus Ave, San Francisco, CA, 94143, USA

    Kathleen R. Lamborn, Susan M. Chang & Michael D. Prados

  5. Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    W. K. Alfred Yung, Mark R. Gilbert & Kenneth Aldape

  6. Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Howard A. Fine

  7. University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI, 53792, USA

    Minesh Mehta & H. Ian Robins

  8. Neuro-Oncology Program, David Geffen School of Medicine at UCLA, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA, 90095, USA

    Timothy F. Cloughesy

  9. Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Janet Dancey

  10. Neuro-Oncology Program, University of Pittsburgh Cancer Institute, 5150 Centre Ave, Pittsburgh, PA, 15232, USA

    Frank Lieberman

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  1. Andrew D. Norden
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  2. Jeffrey J. Raizer
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  3. Lauren E. Abrey
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  10. Minesh Mehta
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  11. Lisa M. DeAngelis
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  12. Timothy F. Cloughesy
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  13. H. Ian Robins
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  14. Kenneth Aldape
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  15. Janet Dancey
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  16. Michael D. Prados
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  17. Frank Lieberman
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  18. Patrick Y. Wen
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Corresponding author

Correspondence to Patrick Y. Wen.

Additional information

This study is conducted on behalf of the North American Brain Tumor Consortium.

Andrew D. Norden and Jeffrey J. Raizer contributed equally to this work.

Frank Lieberman and Patrick Y. Wen contributed equally to this work.

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Norden, A.D., Raizer, J.J., Abrey, L.E. et al. Phase II trials of erlotinib or gefitinib in patients with recurrent meningioma. J Neurooncol 96, 211–217 (2010). https://doi.org/10.1007/s11060-009-9948-7

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  • DOI: https://doi.org/10.1007/s11060-009-9948-7

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