Journal Article

DKFZ-2022-00448

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Treatment outcome of atypical EGFR mutations in the German National Network Genomic Medicine Lung Cancer (nNGM).

Janning, M. (First author)DKFZ* ; Süptitz, J. ; Albers-Leischner, C. ; Delpy, P.DKFZ* ; Tufman, A. ; Velthaus-Rusik, J.-L. ; Reck, M. ; Jung, A.DKFZ* ; Kauffmann-Guerrero, D. ; Bonzheim, I. ; Brändlein, S. ; Hummel, H.-D. ; Wiesweg, M. ; Schildhaus, H.-U. ; Stratmann, J. A. ; Sebastian, M. ; Alt, J. ; Buth, J. ; Esposito, I. ; Berger, J. ; Tögel, L. ; Saalfeld, F. C. ; Wermke, M. ; Merkelbach-Bruse, S. ; Hillmer, A. M. ; Klauschen, F. ; Bokemeyer, C. ; Buettner, R. ; Wolf, J. ; Loges, S. (Last author)DKFZ*

2022
Elsevier Amsterdam [u.a.

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Please use a persistent id in citations: doi:10.1016/j.annonc.2022.02.225

Abstract: Atypical EGFR mutations occur in 10-30% of NSCLC patients with EGFR mutations and their sensitivity to classical EGFR-tyrosine kinase inhibitors (TKI) is highly heterogeneous. Patients harboring one group of uncommon, recurrent EGFR mutations (G719X, S768I, L861Q) respond to EGFR-TKI. Exon 20 insertions are mostly insensitive to EGFR-TKI but display sensitivity to exon 20 inhibitors. Clinical outcome data of patients with very rare point and compound mutations upon systemic treatments are still sparse to date.In this retrospective, multi-center study of the national Network Genomic Medicine (nNGM) in Germany, 856 NSCLC cases with atypical EGFR mutations including co-occuring mutations were reported from 12 centers. Clinical follow-up data after treatment with different EGFR-TKI, chemotherapy and immune checkpoint inhibitors were available from 260 patients. Response to treatment was analyzed in three major groups: (1) uncommon mutations (G719X, S7681, L861Q and combinations), (2) exon 20 insertions and (3) very rare EGFR mutations (very rare single point mutations, compound mutations, exon 18 deletions, exon 19 insertions).Our study comprises the largest thus far reported real-world cohort of very rare EGFR single point and compound mutations treated with different systemic treatments. We validated higher efficacy of EGFR-TKI in comparison to chemotherapy in group 1 (uncommon), while most exon 20 insertions (group 2) were not EGFR-TKI responsive. In addition, we found TKI sensitivity of very rare point mutations (group 3) and of complex EGFR mutations containing exon 19 deletions or L858R mutations independent of the combination partner. Notably, treatment responses in group 3 (very rare) were highly heterogeneous. Co-occurring TP53 mutations exerted a non-significant trend for a detrimental effect on outcome in EGFR-TKI treated patients in groups 2 and 3 but not in group 1.Based on our findings we propose a novel nNGM classification of uncommon EGFR mutations.

Keyword(s): EGFR ; Non-small cell lung cancer ; uncommon EGFR mutations

Note: #EA:A420#LA:A420# / 2022 Jun;33(6):602-615

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Contributing Institute(s):

1. Personalisierte Medizinische Onkologie (A420)
2. Verbundinformationssysteme (E260)
3. DKTK MU LMU zentral (MU01)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2022

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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