% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @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}, }