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Acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) is a prevalent clinical problem in the management of advanced non-small cell lung cancer (NSCLC) with TKI-sensitizing mutations in the EGFR gene. Third-generation EGFR-TKIs have demonstrated potent activity against TKI resistance mediated by the EGFR T790M mutation, and standard re-biopsy and liquid biopsy are utilized to assess the T790M status of the NSCLC patients who experienced progressive disease. Here, we conducted a retrospective study to assess 375 patients whose initial biopsy indicated a TKI-sensitizing mutation (either EGFR 19del or L858R) and who developed progressive disease after treatment with first-generation TKIs, and assayed for T790M status. We adopted a combination approach in which tissue re-biopsy is preferred, utilizing liquid biopsies when tissue re-biopsy is not feasible. We analyzed the potential predictive clinical factors affecting T790M detection, evaluated the standard re-biopsy and liquid biopsy methods in T790M genotyping, and reported the clinical performance of osimertinib. Our results suggested that primary EGFR 19del, brain metastasis, and longer progression-free survival of initial EGFR-TKI treatment are associated with acquired T790M resistance. T790M positive patients significantly benefited from osimertinib. In conclusion, the real-world clinical adoption of the combination approach with both tissue re-biopsy and liquid biopsy for T790M genotyping may provide significant benefits to patients who have developed progressive disease after first-generation TKI treatments.
This article was published in the following journal.
Name: Molecular oncology
Liquid biopsy offers a potential alternative to tissue biopsy for detection of genetic alterations in cancer, and it has been introduced into clinical practice to detect the tyrosine kinase inhibitor ...
After sequential treatment with first- and third-generation EGFR tyrosine kinase inhibitors (TKIs), EGFR-mutant non-small cell lung cancers frequently harbor multiple resistance mutations in exon 20 o...
Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Durvalumab is an anti-PD-L1 monoclonal antibody. The Phase III open-label CAURAL trial (NCT0245...
Lung cancer is the predominant cause of cancer deaths on a worldwide scale. A mutation in the epidermal growth factor receptor (EGFR) can cause non-small cell lung cancer (NSCLC). The L858R one-point ...
Mutations in the EGFR occur in approximately 10-35% of non-small-cell lung cancer (NSCLC) patients. Osimertinib is a third-generation oral small molecule inhibitor of EGFR, active against the common t...
This is a single arm, open label, multicentric proof-of-concept, phase II study in patients with EGFR-mutated non-small-cell lung cancer (NSCLC) with acquired TKI resistance who are "unkno...
The study is being done to determine if non-invasive testing (urine and blood testing) is as effective as tissue testing in identifying epidermal growth factor receptor (EGFR) T790M mutati...
To describe the T790M mutation status of patients with locally advanced/metastatic NSCLC who progressed on previous EGFR TKI treatment in a real-world setting.
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A 1974 Federal act which preempts states' rights with regard to workers' pension benefits and employee benefits. It does not affect the benefits and rights of employees whose employer is self-insured. (From Slee & Slee, Health Care Reform Terms, 1993)
The remuneration paid or benefits granted to an employee.
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GILOTRIF (afatinib) is a kinase inhibitor indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L8...