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@ARTICLE{Janning:179072,
      author       = {M. Janning$^*$ and J. Süptitz and C. Albers-Leischner and
                      P. Delpy$^*$ and A. Tufman and J.-L. Velthaus-Rusik and M.
                      Reck and A. Jung$^*$ and D. Kauffmann-Guerrero and I.
                      Bonzheim and S. Brändlein and H.-D. Hummel and M. Wiesweg
                      and H.-U. Schildhaus and J. A. Stratmann and M. Sebastian
                      and J. Alt and J. Buth and I. Esposito and J. Berger and L.
                      Tögel and F. C. Saalfeld and M. Wermke and S.
                      Merkelbach-Bruse and A. M. Hillmer and F. Klauschen and C.
                      Bokemeyer and R. Buettner and J. Wolf and S. Loges$^*$},
      title        = {{T}reatment outcome of atypical {EGFR} mutations in the
                      {G}erman {N}ational {N}etwork {G}enomic {M}edicine {L}ung
                      {C}ancer (n{NGM}).},
      journal      = {Annals of oncology},
      volume       = {33},
      number       = {6},
      issn         = {0923-7534},
      address      = {Amsterdam [u.a.},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2022-00448},
      pages        = {602-615},
      year         = {2022},
      note         = {#EA:A420#LA:A420# / 2022 Jun;33(6):602-615},
      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.},
      keywords     = {EGFR (Other) / Non-small cell lung cancer (Other) /
                      uncommon EGFR mutations (Other)},
      cin          = {A420 / E260 / MU01},
      ddc          = {610},
      cid          = {I:(DE-He78)A420-20160331 / I:(DE-He78)E260-20160331 /
                      I:(DE-He78)MU01-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35263633},
      doi          = {10.1016/j.annonc.2022.02.225},
      url          = {https://inrepo02.dkfz.de/record/179072},
}