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P3.03 - Biology (Not CME Accredited Session) (ID 969)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Presentations: 1
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
P3.03-07 - Co-Occurring Genomic Alterations in EGFR Altered Chinese Lung Adenocarcinoma Patients (ID 14340)
12:00 - 13:30 | Author(s): Lei Wang
EGFR mutation is one of the most common driver gene mutations in non-small cell lung cancer (NSCLC) patients, especially in adenocarcinoma. Increasing numbers of rare alterations of EGFR such as kinase domain duplication and fusion have been identified with the clinical applications of next generation sequencing (NGS). However, co-occurring genomic alterations of EGFR have not been fully understood in Chinese lung adenocarcinoma patients.a9ded1e5ce5d75814730bb4caaf49419 Method
FFPE tumor and matched blood samples of 989 Chinese patients with confirmed histology subtype of adenocarcinoma, consisting of 503 males and 486 females with a median age of 60 years, were collected for NGS-based 450 cancer genes panel assay. Genomic alterations including single nucleotide variations (SNV), short and long insertions/deletions (Indel), copy number variations (CNV) and gene rearrangements in selected genes were assessed.4c3880bb027f159e801041b1021e88e8 Result
About 57% of Chinese lung adenocarcinoma patients harbored at least one EGFR genomic alteration, which was mainly composed of patient with SNVs and Indels (74%), both gene amplifications and SNVs/Indels (23%), gene amplifications only (2.7%) and gene rearrangements (0.5%). 20% of the patients with SNVs and Indels in EGFR carried more than one EGFR mutations. Moreover, EGFR gene rearrangement was mutually exclusive with other types of genomic alterations.
Exon 19 deletions and L858R substitution were the most common EGFR mutations, which accounted for 37.9% and 33.7% of all EGFR alterations, respectively. Exon 20 insertions, the mostly insensitive variant to EGFR-TKIs, amounted to 3.7%, and the most common resistant alteration T790M accounted for 5.9%. Uncommon EGFR mutations including L861Q, G719X, S768I and others were identified in 18.9% of patients with EGFR mutations.
Further analysis of co-occurring EGFR mutations and kinase receptor fusions revealed that 1.1% (6 of 559) of EGFR mutated Chinese NSCLC patients harbored both EGFR mutations and known druggable kinase receptor fusions including ROS1, RET and NTRK. Three of the six patients received EGFR-TKI as the standard treatment. One patient achieved partial response for 10 months and two achieved stable disease for 5 and 4 months, respectively.8eea62084ca7e541d918e823422bd82e Conclusion
About 38% of Chinese lung adenocarcinoma patients harbored more than one EGFR genomic alterations, and 19% of EGFR mutations identified in Chinese lung adenocarcinoma patients were uncommon mutations. In addition, 1.1% of EGFR mutated patients also harbored known druggable kinase receptor fusions. Though our preliminary data showed that the co-existence of EGFR mutations and kinase receptor fusions might be associated with shorter response time to EGFR-TKIs, further large cohort study is needed to validate this finding.6f8b794f3246b0c1e1780bb4d4d5dc53