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EGFR mutations as a prognostic and predictive marker in non-small-cell lung cancer.

ABSTRACT: Non-small-cell lung cancer (NSCLC) has entered the age of individual treatment, and increasing point mutations of specific oncogenes and rearrangement of some chromosomes are biomarkers used to predict the therapeutic effect of targeted therapy. At present, there is a consensus among clinicians that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown favorable efficacy in NSCLC patients with EGFR mutation, and some relevant research has suggested that the presence of EGFR mutations is a favorable prognostic marker. However, the association of EGFR mutation status with the responsiveness to conventional chemotherapy agents and survival in NSCLC patients is still unclear. This review provides an overview of and assesses the role of EGFR as a prognostic marker for postoperative patients and as a predictive marker for response to cytotoxic chemotherapy. In addition, we review the comparison of response to chemotherapy between EGFR mutations in exon 19 and in exon 21 and the predictive role of p.T790M mutation.

SUBMITTER: Fang S

PROVIDER: S-EPMC4189714 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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EGFR mutations as a prognostic and predictive marker in non-small-cell lung cancer.

Fang Shu S Wang Zhehai Z

Drug design, development and therapy 20140926

Non-small-cell lung cancer (NSCLC) has entered the age of individual treatment, and increasing point mutations of specific oncogenes and rearrangement of some chromosomes are biomarkers used to predict the therapeutic effect of targeted therapy. At present, there is a consensus among clinicians that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown favorable efficacy in NSCLC patients with EGFR mutation, and some relevant research has suggested that the presenc ...[more]

PMID: 25302015

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Project description:BackgroundEpidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard treatments for advanced EGFR-mutated non-small cell lung cancer (NSCLC) patients. Osimertinib is an effective therapy for NSCLC patients with acquired resistance due to T790M mutation after first- and second-generation EGFR-TKI treatment. This study aimed to analyze the clinical outcomes of sequential therapy following first-line EGFR-TKIs and the predictive factors of an acquired T790M mutation.MethodsBetween January 2014 and December 2018, data from 2190 advanced NSCLC patients with common EGFR mutations (exon 19 deletion and L858R) receiving first- and second-generation EGFR-TKIs in Linkou, Kaohsiung, Chiayi and Keelung Chang Gung Memorial Hospitals were retrospectively retrieved and analyzed.ResultsUntil August 2021, among 1943 patients who experienced progressive disease, 526 underwent T790M mutation tests, and their T790M-positive rate was 53.6%. Exon 19 deletion mutation and progression-free survival (PFS) of >12 months were positively associated with secondary T790M mutation. Different first-line first- and second-generation EGFR-TKI therapies did not affect the appearance of acquired T790M mutations. The median overall survival (OS) was 58.3 [95% confidence interval (CI): 49.0-67.5] months among the patients with T790M mutation who received second-line osimertinib therapy compared with 31.0 (95% CI: 27.5-34.5) months among the patients without T790M mutation who received chemotherapy alone. The multivariate analysis showed that a poor performance status (score: >2), nonadenocarcinoma histology, stage IV cancer, liver metastasis, brain metastasis, PFS while on first-line EGFR-TKIs, and subsequent chemotherapy without third-generation EGFR-TKIs were significant independent unfavorable prognostic factors for OS.ConclusionThis study demonstrated the efficacy of first-line EGFR-TKIs and sequential osimertinib therapy. The results of our study suggest that T790M mutation tests are important for the use of subsequent osimertinib, which yielded favorable survival outcomes.

Dataset Information

EGFR mutations as a prognostic and predictive marker in non-small-cell lung cancer.

Publications

EGFR mutations as a prognostic and predictive marker in non-small-cell lung cancer.

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