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000179072 0247_ $$2doi$$a10.1016/j.annonc.2022.02.225
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000179072 041__ $$aEnglish
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000179072 1001_ $$0P:(DE-He78)0ef2b2f1cc7d11216e67ab9dc6599b31$$aJanning, Melanie$$b0$$eFirst author$$udkfz
000179072 245__ $$aTreatment outcome of atypical EGFR mutations in the German National Network Genomic Medicine Lung Cancer (nNGM).
000179072 260__ $$aAmsterdam [u.a.$$bElsevier$$c2022
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000179072 500__ $$a#EA:A420#LA:A420# / 2022 Jun;33(6):602-615
000179072 520__ $$aAtypical 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.
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000179072 650_7 $$2Other$$aEGFR
000179072 650_7 $$2Other$$aNon-small cell lung cancer
000179072 650_7 $$2Other$$auncommon EGFR mutations
000179072 7001_ $$aSüptitz, J.$$b1
000179072 7001_ $$aAlbers-Leischner, C.$$b2
000179072 7001_ $$0P:(DE-He78)a1f51aac6b23daf72353f16ad266d640$$aDelpy, P.$$b3$$udkfz
000179072 7001_ $$aTufman, A.$$b4
000179072 7001_ $$aVelthaus-Rusik, J-L$$b5
000179072 7001_ $$aReck, M.$$b6
000179072 7001_ $$0P:(DE-He78)8649a248223437c9ddfd2df8c2049bd0$$aJung, Andreas$$b7$$udkfz
000179072 7001_ $$aKauffmann-Guerrero, D.$$b8
000179072 7001_ $$aBonzheim, I.$$b9
000179072 7001_ $$aBrändlein, S.$$b10
000179072 7001_ $$aHummel, H-D$$b11
000179072 7001_ $$aWiesweg, M.$$b12
000179072 7001_ $$aSchildhaus, H-U$$b13
000179072 7001_ $$aStratmann, J. A.$$b14
000179072 7001_ $$aSebastian, M.$$b15
000179072 7001_ $$aAlt, J.$$b16
000179072 7001_ $$aButh, J.$$b17
000179072 7001_ $$aEsposito, I.$$b18
000179072 7001_ $$aBerger, J.$$b19
000179072 7001_ $$aTögel, L.$$b20
000179072 7001_ $$aSaalfeld, F. C.$$b21
000179072 7001_ $$aWermke, M.$$b22
000179072 7001_ $$aMerkelbach-Bruse, S.$$b23
000179072 7001_ $$aHillmer, A. M.$$b24
000179072 7001_ $$aKlauschen, F.$$b25
000179072 7001_ $$aBokemeyer, C.$$b26
000179072 7001_ $$aBuettner, R.$$b27
000179072 7001_ $$aWolf, J.$$b28
000179072 7001_ $$0P:(DE-He78)1eee9e84c0f8c90a97fe40b6e8252a23$$aLoges, Sonja$$b29$$eLast author$$udkfz
000179072 773__ $$0PERI:(DE-600)2003498-2$$a10.1016/j.annonc.2022.02.225$$gp. S0923753422003611$$n6$$p602-615$$tAnnals of oncology$$v33$$x0923-7534$$y2022
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