Oncology research and treatment · 2015
Mutation Profiling of Lung Cancers with Long-Term Response to Gefitinib Therapy.
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Gautschi Oliver, Stadelmann Carola, Aebersold-Keller Franziska, König Katharina, Büttner Reinhard, Heukamp Lukas C, Betticher Daniel, Baumann Christa, Buser Katharina, Calderoni Antonello, Casty Adrian, DʼAddario Giannicola, Irlé Claudius, Mamot Christoph, Morant Rudolf, Trojan Andreas, Pellicioli Erica, Jehle-Schwertfeger Sonja, Aebi Stefan, Diebold Joachim
Аннотация
BACKGROUND: The role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and unknown EGFR mutation status has recently been questioned.
PATIENTS AND METHODS: We conducted a retrospective study of patients with unknown EGFR mutation status and long-term response (LTR) to gefitinib in the Swiss Iressa expanded access program (EAP). We assessed patient characteristics, and performed Sanger sequencing and next generation sequencing on archived tumor tissue. We hypothesized that EGFR mutations are prevalent in patients with LTR.
RESULTS: Of 430 patients in the EAP, 18 (4%) fulfilled our definition of LTR, and 16 of them had archived tumor tissue. Patient characteristics were as expected for age, sex, and smoking history. Median duration of therapy was 38 months (range 24-142 months). Sanger sequencing revealed EGFR exon 18-21 mutations in 6 (38%) of the tumors. Next generation sequencing revealed no further EGFR-mutated cases, but reported in 15 (94%) of the tumors mutations in other genes (ALK, BRAF, DDR2, KEAP1, MET, PTEN, STK11) previously associated with NSCLC.
CONCLUSION: Larger studies are needed to define the prognostic values of different driver mutations in patients with NSCLC.
PATIENTS AND METHODS: We conducted a retrospective study of patients with unknown EGFR mutation status and long-term response (LTR) to gefitinib in the Swiss Iressa expanded access program (EAP). We assessed patient characteristics, and performed Sanger sequencing and next generation sequencing on archived tumor tissue. We hypothesized that EGFR mutations are prevalent in patients with LTR.
RESULTS: Of 430 patients in the EAP, 18 (4%) fulfilled our definition of LTR, and 16 of them had archived tumor tissue. Patient characteristics were as expected for age, sex, and smoking history. Median duration of therapy was 38 months (range 24-142 months). Sanger sequencing revealed EGFR exon 18-21 mutations in 6 (38%) of the tumors. Next generation sequencing revealed no further EGFR-mutated cases, but reported in 15 (94%) of the tumors mutations in other genes (ALK, BRAF, DDR2, KEAP1, MET, PTEN, STK11) previously associated with NSCLC.
CONCLUSION: Larger studies are needed to define the prognostic values of different driver mutations in patients with NSCLC.
Предметные рубрики MeSH
AdultAge DistributionAgedAntineoplastic AgentsBiomarkers, TumorCarcinoma, Non-Small-Cell LungDNA Mutational AnalysisErbB ReceptorsFemaleGefitinibGene Expression ProfilingGenetic MarkersHumansLongitudinal StudiesLung NeoplasmsMaleMiddle AgedPolymorphism, Single NucleotidePrevalenceQuinazolinesRetrospective StudiesRisk FactorsSex DistributionSmokingSwitzerlandTreatment Outcome