TY  - JOUR
A1  - Janning, Melanie
A1  - Süptitz, Juliane
A1  - Albers-Leischner, Corinna
A1  - Delpy, Pierre
A1  - Tufman, Amanda L. H.
A1  - Velthaus-Rusik, Janna-Lisa
A1  - Reck, Martin
A1  - Jung, Andreas
A1  - Kauffmann-Guerrero, Diego
A1  - Bonzheim, Irina
A1  - Brändlein, Stephanie
A1  - Hummel, Horst-Dieter
A1  - Wiesweg, Marcel
A1  - Schildhaus, Hans-Ulrich
A1  - Stratmann, Jan Alexander
A1  - Sebastian, Martin
A1  - Alt, Jürgen
A1  - Buth, Juliane
A1  - Esposito, Irene
A1  - Berger, Johannes
A1  - Tögel, Lars
A1  - Saalfeld, Felix
A1  - Wermke, Martin
A1  - Merkelbach-Bruse, Sabine
A1  - Hillmer, Axel Maximilian
A1  - Klauschen, Frederick
A1  - Bokemeyer, Carsten
A1  - Büttner, Reinhard
A1  - Wolf, Jürgen
A1  - Loges, Sonja
T1  - Treatment outcome of atypical EGFR mutations in the German National Network Genomic Medicine Lung Cancer (nNGM)
T2  - Annals of oncology
N2  - Background: Atypical EGFR mutations occur in 10%-30% of non-small-cell lung cancer (NSCLC) patients with EGFR mutations and their sensitivity to classical epidermal growth factor receptor (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.
Patients and methods: In this retrospective, multicenter study of the national Network Genomic Medicine (nNGM) in Germany, 856 NSCLC cases with atypical EGFR mutations including co-occurring mutations were reported from 12 centers. Clinical follow-up data after treatment with different EGFR-TKIs, chemotherapy and immune checkpoint inhibitors were available from 260 patients. Response to treatment was analyzed in three major groups: (i) uncommon mutations (G719X, S7681, L861Q and combinations), (ii) exon 20 insertions and (iii) very rare EGFR mutations (very rare single point mutations, compound mutations, exon 18 deletions, exon 19 insertions).
Results: 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.
Conclusions: Based on our findings, we propose a novel nNGM classification of atypical EGFR mutations.
KW  - non-small-cell lung cancer
KW  - EGFR
KW  - atypical EGFR mutations
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63117
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-631177
SN  - 0923-7534
SN  - 1569-8041
N1  - This work was supported by German Cancer Aid (Deutsche Krebshilfe) [grant numbers 70112835, 70113510 and 70114428 to nNGM], the Hector Foundation II (no grant number) to SL and the Margarete Clemens Stiftung (no grant number) to MJ.
VL  - 33
IS  - 6
SP  - 602
EP  - 615
PB  - Elsevier
CY  - Amsterdam [u.a.]
ER  -