Impact of Concomitant Genetic Alterations in EGFR Mutated Adenocarcinoma by NGS Analysis: A Multicenter Study
- Conditions
- EGFR Activating MutationAdenocarcinoma of Lung
- Registration Number
- NCT04122833
- Lead Sponsor
- Konkuk University Medical Center
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 80
- 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
Tumor tissue from bone metastases that have been decalcified are not acceptable.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Change of mutation profiles between pre/post TKI treatment through study completion, an average of 1 year Comparison of the kinds of the mutation between pre- and post TKI treatment
- Secondary Outcome Measures
Name Time Method The number and the kinds of co-occurring mutations on tumors before and after TKI treatment through study completion, an average of 1 year 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
Tumor mutation burden in tumors tissues before and after TKI treatment through study completion, an average of 1 year The investigators will compare the TMB in tumors tissues before and after TKI
PFS according to the co-occurring mutations with pre-TKI treatment through study completion, an average of 1 year 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
The correlation between the change of variant allele frequency(VAF) and drug response in matched tumors tissues before and after TKI treatment through study completion, an average of 1 year The investigators will analyze the correlation with the change of the VAF and PFS in matched tumors tissues before and after TKI treatment
The concordance the the mutation profiles in the NGS results of tissue and blood in the same patients through study completion, an average of 1 year The investigators will compare the concordance of the mutation profile in tumors and blood before TKI treatment
Trial Locations
- Locations (2)
Asan medical center
🇰🇷Seoul, Korea, Republic of
Catholic university medical center, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of