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Epidermal growth factor receptor (EGFR) amplification rates observed in screening patients for randomized trials in glioblastoma

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Abstract

Purpose

Epidermal growth factor receptor (EGFR) amplification has been reported to occur in ~ 50% of glioblastomas (GBMs). We are conducting several global studies that require central testing for EGFR amplification during screening, representing an opportunity to confirm the frequency of amplification in GBM in a large cohort and to evaluate whether EGFR amplification differs by region of the world.

Methods

EGFR amplification was measured by fluorescence in situ hybridization during screening for therapeutic trials of an EGFR antibody–drug conjugate: two Phase 2/3 global trials (INTELLANCE-1, INTELLANCE-2), and a Japanese Phase 1/2 trial (INTELLANCE-J). We evaluated the proportion of tumor tissue samples harboring EGFR amplification among those tested and differences in amplification frequency by geography.

Results

EGFR was amplified in 54% of 3150 informative cases screened for INTELLANCE-1 and -2, consistent with historic controls, but was significantly lower in patients from Asia versus the rest of the world (35% vs. 56%, P < 0.0030). The independent INTELLANCE-J trial validated this finding (33% amplified of 153 informative cases).

Conclusions

EGFR amplification occurs less frequently in patients from Asia than elsewhere. Further study is required to understand biological differences to optimize treatment in glioblastoma.

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Acknowledgements

The authors and AbbVie would like to thank patients and their families/caregivers; study investigators and staff; Mrinal Y. Shah, PhD for medical writing support, and Yan Sun, PhD for statistical support, both employees of AbbVie, Inc.

Funding

AbbVie provided financial support for these studies (NCT02573324, NCT02343406, NCT02590263) and participated in the design, study conduct, analysis and interpretation of the data, as well as the writing, review, and approval of the manuscript. All authors were involved in the data gathering, analysis, review, interpretation and manuscript preparation and approval. A.B. Lassman was supported in part Voices Against Brain Cancer, the William Rhodes and Louise Tilzer-Rhodes Center for Glioblastoma at NewYork-Presbyterian Hospital, and grants P30CA013696 and UG1CA189960 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute/National Institutes of Health.

Author information

Author notes

  1. Michael A. Vogelbaum

    Present address: Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, FL, USA

  2. Peixin Zhang

    Present address: Jazz Pharmaceuticals, Inc, Philadelphia, PA, USA

Authors and Affiliations

  1. Department of Neurology & Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 710 West 168th Street, New York, NY, 10032, USA

    Andrew B. Lassman

  2. Department of Pathology, Toronto General Hospital/Research Institute, Toronto, ON, Canada

    Kenneth D. Aldape

  3. Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    Kenneth D. Aldape

  4. Abbvie, Inc, North Chicago, IL, USA

    Peter J. Ansell, Earle Bain, Jim Looman, Christopher Ocampo & Lisa Roberts-Rapp

  5. Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Walter J. Curran

  6. Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

    Marica Eoli

  7. Department of Neurology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands

    Pim J. French & Martin J. van den Bent

  8. Department of Neurosurgery, Osaka International Cancer Institute, Osaka, Japan

    Manabu Kinoshita

  9. Miami Cancer Institute, Baptist Hospital, Miami, FL, USA

    Minesh Mehta

  10. Tokyo Women’s Medical University Hospital, Shinjuku-ku, Tokyo, Japan

    Yoshihiro Muragaki

  11. Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan

    Yoshitaka Narita

  12. Abbott Molecular, Des Plaines, IL, USA

    Minghao Song

  13. Burkhardt Brain Tumor Center, Cleveland Clinic, Cleveland, OH, USA

    Michael A. Vogelbaum

  14. Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Annemiek M. E. Walenkamp

  15. Department of Radiation Oncology & Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA

    Tony J. C. Wang

  16. RTOG Foundation Statistics and Data Management Center, American College of Radiology, Philadelphia, PA, USA

    Peixin Zhang

Authors
  1. Andrew B. Lassman
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  2. Kenneth D. Aldape
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  6. Marica Eoli
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  9. Jim Looman
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  10. Minesh Mehta
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  11. Yoshihiro Muragaki
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  12. Yoshitaka Narita
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  14. Lisa Roberts-Rapp
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  15. Minghao Song
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  16. Michael A. Vogelbaum
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  19. Peixin Zhang
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  20. Martin J. van den Bent
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Contributions

Contribution to study design—ABL, PJA, EB, WC, PJF, JL, MM, CO, MAV, TJCW, PZ, MJvdB. Study conduct and patient treatment—ABL, KDA, EB, WC, ME, MK, JL, YM, YN, CO, MAV, AMEW, TJCW, MJvdB. Data collection, analysis, and interpretation—ABL, PJA, LRR, MS, MJvdB. Manuscript review and approval of the final version for submission—All authors.

Corresponding author

Correspondence to Andrew B. Lassman.

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Conflict of interest

Andrew B. Lassman: In the last 36 months, Dr. Lassman reports grants, personal fees and non-financial support from AbbVie, during the conduct of the study; personal fees and non-financial support from Orbus, grants, personal fees and non-financial support from Karyopharm, personal fees and non-financial support from NW Biotherapeutics, grants and non-financial support from Oncoceutics, personal fees and non-financial support from Agios, personal fees and non-financial support from Celgene, personal fees and non-financial support from Novocure, non-financial support from Tocagen, non-financial support from BMS, grants, personal fees and non-financial support from Kadmon, grants, personal fees and non-financial support from Roche/Genentech, grants and non-financial support from Amgen, grants and non-financial support from Millenium, grants and non-financial support from Celldex, grants and non-financial support from Novartis, grants and non-financial support from Pfizer, non-financial support from Keryx/Aeterna Zentaris, grants and non-financial support from VBI Vaccines, grants and non-financial support from Beigene, personal fees from Bioclinica as an expert blinded independent reviewer of clinical and imaging data for a BMS-sponsored trial, personal fees from prIME Oncology, personal fees from Sapience, personal fees from WebMD, personal fees from Physicians' Education Resource/Chemotherapy Foundation Symposium, personal fees from Astra Zeneca, personal fees from Cortice, outside the submitted work. Kenneth D. Aldape: Nothing to disclose. Peter J. Ansell, Earle Bain, Jim Looman, Christopher Ocampo, Lisa Roberts-Rapp: Employees of AbbVie and may own stock/options. Walter J. Curran: Consultant for AstraZeneca and BMS; ownership shares of Nanthealth. Marica Eoli: Nothing to disclose. Pim J. French: Research funding from AbbVie. Manabu Kinoshita: Honoraria from Eisai, BrainLab, Nihon Medi-Physics, Canon Medical Systems, Integra Japan, Novocure, Daiichi-Sankyo, Chugai; research grants from Chugai, Daiichi-Sankyo, Takeda, Ohtsuka. Minesh Mehta: Consultant for Agenus, Insys, Remedy, IBA, Varian, Celgene, AbbVie, AstraZeneca, Tocagen, Blue Earth Diagnostics; board of directors with stock options, Oncoceutics. Yoshihiro Muragaki: Consulting/advisory role for AbbVie, Daiichi Sankyo; speakers’ bureau for MSD, Daiichi Sankyo, Chugai Pharma, Otsuka, Eisai, Novartis, Hitachi, Bristol-Myers Squibb Japan; research funding to institution from MSD, Daiichi Sankyo, Chugai Pharma, Otsuka, Eisai, Hitachi. Yoshitaka Narita: Grants and lectures fees from Chugai Pharmaceutical Co., Ono Pharmaceutical Co., AbbVie, Dainippon-Sumitomo, Daiichi Sankyo, Eisai, Stella-Pharma, Ohtuka, Meiji-Seika, SBI Pharma. Minghao Song: Employee of Abbott Molecular and may own stock/options. Michael A. Vogelbaum: Indirect equity and royalty interests in Infuseon Therapeutics, Inc. Annemiek Walenkamp: Research grants from Novartis, Ipsen; advisory board member for Ipsen, Novartis, Polyphor, Karyopharm; study budget from Karyopharm, BMS, Genzyme, Roche. Tony J. C. Wang: Personal fees and non-financial support from AbbVie; outside of the submitted work, consultant for Elekta, Merck, Doximity; advisory board and travel expenses for Novocure, AstraZeneca; honoraria from Elekta, Cancer Panels; stock options from Doximity; royalties from Wolters Kluwer. Peixin Zhang: Nothing to disclose. Martin J. van den Bent: Personal fees from AbbVie, Celgene, Genenta, BMS, Agios, Boehringer Ingelheim; research funding from AbbVie.

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Lassman, A.B., Aldape, K.D., Ansell, P.J. et al. Epidermal growth factor receptor (EGFR) amplification rates observed in screening patients for randomized trials in glioblastoma. J Neurooncol 144, 205–210 (2019). https://doi.org/10.1007/s11060-019-03222-y

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