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Cancer Research and Treatment > Epub ahead of print
doi: https://doi.org/10.4143/crt.2023.1177    [Epub ahead of print]
Comparison of Clinicopathogenomic Features and Treatment Outcomes of EGFR and HER2 Exon 20 Insertion Mutations in Non–Small Cell Lung Cancer: Single-Institution Experience
So Heun Lee1 , Hyehyun Jeong1 , Deok Hoon Kim2, Se Jin Jang2, Sang-We Kim1, Shinkyo Yoon1, Dae Ho Lee1
1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
2Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Correspondence  Dae Ho Lee ,Tel: 82-2-3010-3214, Fax: 82-2-3010-6961, Email: leedaeho@amc.seoul.kr
Received: November 1, 2023;  Accepted: January 28, 2024.  Published online: January 30, 2024.
*So Heun Lee and Hyehyun Jeong contributed equally to this work.
Exon 20 insertion mutations (E20ins) in epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) in non–small cell lung cancer (NSCLC) patients has become more important with emergence of novel agents targeting E20ins.
Materials and Methods
Advanced/Metastatic NSCLC patients with E20ins were included. EGFR E20ins was identified by two methods, next-generation sequencing (NGS) or real-time polymerase chain reaction (PCR), while HER2 E20ins was done by NGS only.
Between December 2013 and July 2021, E20ins were identified in 107 patients at Asan Medical Center; 67 EGFR E20ins and 40 HER2 E20ins. Out of 32 patients with EGFR E20ins who had tested both PCR and NGS, 17 were identified only through NGS and the other 15 through both tests, giving a discordance rate of 53.1%. There was no clinically significant difference in clinicopathologic features between EGFR and HER2 E20ins; both were observed more frequently in adenocarcinoma, female and never-smokers. Brain metastases were evident at diagnosis in 31.8% of EGFR E20ins and 27.5% of HER2 E20ins, respectively. Platinum-based doublets demonstrated objective response rates (ORR) of 13.3% with a median progression-free survival (PFS) of 4.2 months for EGFR E20ins and 35.3% with 4.7 months for HER2 E20ins, respectively. In contrast, novel EGFR E20ins-targeted agents exhibited an ORR of 46.2% with a median PFS of 5.4 months, while HER2-targeted agents showed an ORR of 50% with that of 7.0 months.
Identification of EGFR and HER2 E20ins is more important as their targeted therapies improved outcomes. Upfront NGS test as a comprehensive molecular approach is strongly warranted.
Key words: Non-small-cell lung carcinoma, Exon 20 insertion, EGFR, HER2, Targeted therapy
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