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@ARTICLE{Kraskowski:276100,
      author       = {O. Kraskowski and J. A. Stratmann and M. Wiesweg and W.
                      Eberhardt and M. Metzenmacher and K. W. Schmid$^*$ and T.
                      Herold and H.-U. Schildhaus$^*$ and K. Darwiche and C.
                      Aigner$^*$ and M. Stuschke$^*$ and K. Laue and G. Zaun and
                      S. Kasper$^*$ and J. Hense and M. Sebastian$^*$ and M.
                      Schuler$^*$ and M. Pogorzelski},
      title        = {{F}avorable survival outcomes in epidermal growth factor
                      receptor ({EGFR})-mutant non-small cell lung cancer
                      sequentially treated with a tyrosine kinase inhibitor and
                      osimertinib in a real-world setting.},
      journal      = {Journal of cancer research and clinical oncology},
      volume       = {149},
      number       = {11},
      issn         = {0301-1585},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2023-01000},
      pages        = {9243-9252},
      year         = {2023},
      note         = {2023 Sep;149(11):9243-9252},
      abstract     = {EGFR tyrosine kinase inhibitor (TKI) therapy in
                      EGFR-mutated lung cancer is limited by acquired resistance.
                      In half of the patients treated with first/second-generation
                      (1st/2nd gen) TKI, resistance is associated with EGFR
                      p.T790M mutation. Sequential treatment with osimertinib is
                      highly active in such patients. Currently, there is no
                      approved targeted second-line option for patients receiving
                      first-line osimertinib, which thus may not be the best
                      choice for all patients. The present study aimed to evaluate
                      the feasibility and efficacy of a sequential TKI treatment
                      with 1st/2nd gen TKI, followed by osimertinib in a
                      real-world setting.Patients with EGFR-mutated lung cancer
                      treated at two major comprehensive cancer centers were
                      retrospectively analyzed by the Kaplan-Meier method and log
                      rank test.A cohort of 150 patients, of which 133 received
                      first-line treatment with a first/second gen EGFR TKI, and
                      17 received first-line osimertinib, was included. Median age
                      was 63.9 years, $55\%$ had ECOG performance score of ≥ 1.
                      First-line osimertinib was associated with prolonged
                      progression-free survival (P = 0.038). Since the approval of
                      osimertinib (February 2016), 91 patients were under
                      treatment with a 1st/2nd gen TKI. Median overall survival
                      (OS) of this cohort was 39.3 months. At data cutoff, $87\%$
                      had progressed. Of those, $92\%$ underwent new biomarker
                      analyses, revealing EGFR p.T790M in $51\%.$ Overall, $91\%$
                      of progressing patients received second-line therapy, which
                      was osimertinib in $46\%.$ Median OS with sequenced
                      osimertinib was 50 months. Median OS of patients with
                      p.T790M-negative progression was 23.4 months.Real-world
                      survival outcomes of patients with EGFR-mutated lung cancer
                      may be superior with a sequenced TKI strategy. Predictors of
                      p.T790M-associated resistance are needed to personalize
                      first-line treatment decisions.},
      keywords     = {EGFR T790M mutation (Other) / EGFR-mutated NSCLC (Other) /
                      Osimertinib (Other) / Rebiopsy (Other) / Second line (Other)
                      / Sequential therapy (Other)},
      cin          = {ED01 / FM01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331 / I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37198447},
      doi          = {10.1007/s00432-023-04839-3},
      url          = {https://inrepo02.dkfz.de/record/276100},
}