Impact of Concomitant Genetic Alterations in EGFR Mutated Adenocarcinoma by NGS Analysis: A Multicenter Study

Study Overview
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Brief Summary
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The concomitant co-mutation with epidermal growth factor receptor (EGFR) mutation might influence the clinical outcomes. The investigators will identify the impact of concommitant mutation on clinical outcome in patients with advanced -EGFR mutated adenocarcinoma. The investigators will compare the genetic alterations between tumors of pre and post Tyrosin Kinase Inhibitor(TKI) treatments and predict the resistance mechanism for EGFR-TKIs by next-generation sequencing(NGS) analysis.

Detailed Description
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The current standard therapies in the treatment of advanced EGFR-mutated lung cancer patients are the 1st or 2nd EGFR-TKIs. Although 70-80% of patients treated by EGFR-TKIS show good responses, they have progression after around 12 months. The concomitant co-mutation with EGFR mutation might influence the drug response of EGFR TKI. The investigators will compare the progression-free survival (PFS) of EGFR-TKI according to co-occuring mutations. The patients experience the change of molecular profiles after using the TKI. Therefore, the investigators will investigate the molecular profiles through NGS panel with foundation medicine in the tissue of pre/post EGFR-TKI, compare the change of the molecular profiles and tumor mutation burden(TMB), and identify novel mechanisms of drug resistance. The investigators will collect the tumor tissues and blood of around 80 patients in multi-centers prospectively. Then, They will be sent to FoundationOne in the US and perform NGS analysis. The type of EGFR-TKIs would be selected according to physicians' preference. NGS will be performed twice before the EGFR-TKIs treatment and after the progression.

Official Title
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A Next-generation Sequencing Analysis to Investigate the Clinical Impact of Concomitant Genetic Alterations in the Patients With Advanced EGFR-mutated Lung Adenocarcinoma: A Multicenter Study.

Conditions
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Adenocarcinoma of Lung, EGFR Activating Mutation

Intervention / Treatment
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* Other: Next generation sequencing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Form Age ≥19 years EGFR-mutated stage IV lung adenocarcinoma patients Archival biopsy tissues which are from core needle biopsies, endobronchial ultrasound (EBUS) guided- lymph node biopsy or lymph node excisional biopsy at baseline and at radiologic progression Availability of the 10 unstained slides and 1 H&E slides at pre/ post TKI treatment Samples should contain a minimum of 20% viable tumor cells that preserve Exclusion Criteria: Tumor tissue from bone metastases that have been decalcified are not acceptable. -

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Next generation sequencing|observational study|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of mutation profiles between pre/post TKI treatment | Comparison of the kinds of the mutation between pre- and post TKI treatment | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS according to the co-occurring mutations with pre-TKI treatment | The investigators will compared the PFS according to the kinds of co-occuring genetic alteration in patient with EGFR -mutated adenocarcinoma before the EGFR TKI treatment | through study completion, an average of 1 year | 
| The number and the kinds of co-occurring mutations on tumors before and after TKI treatment | The investigators will collect the information about the number and the kinds of co-occurring mutations on tumors before and after TKI treatment in Foundation medicine NGS | through study completion, an average of 1 year | 
| The correlation between the change of variant allele frequency(VAF) and drug response in matched tumors tissues before and after TKI treatment | The investigators will analyze the correlation with the change of the VAF and PFS in matched tumors tissues before and after TKI treatment | through study completion, an average of 1 year | 
| Tumor mutation burden in tumors tissues before and after TKI treatment | The investigators will compare the TMB in tumors tissues before and after TKI | through study completion, an average of 1 year | 
| The concordance the the mutation profiles in the NGS results of tissue and blood in the same patients | The investigators will compare the concordance of the mutation profile in tumors and blood before TKI treatment | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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next generation sequencing