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

• Type of Material: Article
• Authors: Andrew B. Lassman, Columbia University; Kenneth D. Aldape, Toronto General Hospital; Peter J. Ansell, Abbvie Inc; Earle Bain, Abbvie Inc; Walter Curran Jr, Emory University; Marica Eoli, Fondazione IRCCS Istituto Neurologico Carlo Besta; Pim J. French, Erasmus MC Cancer Institute; Manabu Kinoshita, Osaka International Cancer Institute; Jim Looman, Abbvie Inc; Minesh Mehta, Baptist Hospital Miami; Yoshihiro Muragaki, Tokyo Womens Medical University Hospital; Yoshitaka Narita, National Cancer Center Hospital; Christopher Ocampo, Abbvie Inc; Lisa Roberts-Rapp, Abbvie Inc; Minghao Song, Abbott Molecular; Michael A. Vogelbaum, Cleveland Clinic; Annemiek M. E. Walenkamp, University of Groningen; Tony J. C. Wang, Columbia University; Peixin Zhang, American College of Radiology; Martin J. van den Bent, Erasmus MC Cancer Institute
• Language: English
• Date: 2019-08-01
• Publisher: Springer
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 Springer Nature Switzerland AG. Part of Springer Nature.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1007/s11060-019-03222-y
• Title of Journal or Parent Work: Journal of Neuro-Oncology
• Volume: 144
• Issue: 1
• Start Page: 205
• End Page: 210
• Grant/Funding Information: 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.; 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.; ABL was supported in part by NIH/NCI Cancer Center Support Grants P30CA013696 and 5UG1CA189960.
• Keywords: Biomarker; Neurosciences & Neurology; Mutations; Oncology; Depatux-m; Screening; Cell lung-cancer; EGFR; Expression; GBM; Science & Technology; Clinical Neurology; IDH1; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Neuroscience; Health Sciences, Oncology; Health Sciences, Pathology

Abstract

Purpose 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 vs 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.