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

Andrew B Lassman¹, Kenneth D Aldape^{2

3}, Peter J Ansell⁴, Earle Bain⁴, Walter J Curran⁵, Marica Eoli⁶, Pim J French⁷, Manabu Kinoshita⁸, Jim Looman⁴, Minesh Mehta⁹, Yoshihiro Muragaki¹⁰, Yoshitaka Narita¹¹, Christopher Ocampo⁴, Lisa Roberts-Rapp⁴, Minghao Song¹², Michael A Vogelbaum^{13

14}, Annemiek M E Walenkamp¹⁵, Tony J C Wang¹⁶, Peixin Zhang^{17

18}, Martin J van den Bent⁷

Affiliations

¹ Department of Neurology & Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 710 West 168th Street, New York, NY, 10032, USA. ABL7@cumc.columbia.edu.
² Department of Pathology, Toronto General Hospital/Research Institute, Toronto, ON, Canada.
³ Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
⁴ Abbvie, Inc, North Chicago, IL, USA.
⁵ Winship Cancer Institute, Emory University, Atlanta, GA, USA.
⁶ Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
⁷ Department of Neurology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
⁸ Department of Neurosurgery, Osaka International Cancer Institute, Osaka, Japan.
⁹ Miami Cancer Institute, Baptist Hospital, Miami, FL, USA.
¹⁰ Tokyo Women's Medical University Hospital, Shinjuku-ku, Tokyo, Japan.
¹¹ Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
¹² Abbott Molecular, Des Plaines, IL, USA.
¹³ Burkhardt Brain Tumor Center, Cleveland Clinic, Cleveland, OH, USA.
¹⁴ Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, FL, USA.
¹⁵ Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁶ Department of Radiation Oncology & Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.
¹⁷ RTOG Foundation Statistics and Data Management Center, American College of Radiology, Philadelphia, PA, USA.
¹⁸ Jazz Pharmaceuticals, Inc, Philadelphia, PA, USA.

PMID: 31273577
PMCID: PMC8082754
DOI: 10.1007/s11060-019-03222-y

Clinical Trial

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

Andrew B Lassman et al. J Neurooncol. 2019 Aug.

. 2019 Aug;144(1):205-210.

doi: 10.1007/s11060-019-03222-y. Epub 2019 Jul 4.

Authors

Affiliations

¹ Department of Neurology & Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 710 West 168th Street, New York, NY, 10032, USA. ABL7@cumc.columbia.edu.
² Department of Pathology, Toronto General Hospital/Research Institute, Toronto, ON, Canada.
³ Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
⁴ Abbvie, Inc, North Chicago, IL, USA.
⁵ Winship Cancer Institute, Emory University, Atlanta, GA, USA.
⁶ Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
⁷ Department of Neurology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
⁸ Department of Neurosurgery, Osaka International Cancer Institute, Osaka, Japan.
⁹ Miami Cancer Institute, Baptist Hospital, Miami, FL, USA.
¹⁰ Tokyo Women's Medical University Hospital, Shinjuku-ku, Tokyo, Japan.
¹¹ Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
¹² Abbott Molecular, Des Plaines, IL, USA.
¹³ Burkhardt Brain Tumor Center, Cleveland Clinic, Cleveland, OH, USA.
¹⁴ Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, FL, USA.
¹⁵ Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁶ Department of Radiation Oncology & Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.
¹⁷ RTOG Foundation Statistics and Data Management Center, American College of Radiology, Philadelphia, PA, USA.
¹⁸ Jazz Pharmaceuticals, Inc, Philadelphia, PA, USA.

PMID: 31273577
PMCID: PMC8082754
DOI: 10.1007/s11060-019-03222-y

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.

Keywords: Biomarker; Depatux-m; EGFR; GBM; Screening.

PubMed Disclaimer

References

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

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

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