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Epidemiological characteristics and therapeutic advances of EGFR exon 20 insertion mutations in non-small cell lung
Binyang Pan1, Jiaqi Liang1, Haochun Shi1
1Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Abstract:
The third most prevalent type of epidermal growth factor receptor (EGFR) mutation, EGFR exon 20 insertions (EGFRex20ins), involves 2%-12% of all cases of EGFR-positive non-small cell lung cancer (NSCLC). Approximately 90% of the mutations occur within the loop structure region, and the most frequently reported subtypes are A767_V769dup and S768_D770dup, which together account for almost 50% of instances. Apart from the unique subtype of A763_Y764insFQEA, NSCLCs with EGFRex20ins are resistant to approved EGFR tyrosine kinase inhibitors (TKIs) and are also insensitive to chemotherapy or immunotherapy. A new modality of treatment for NSCLC patients with EGFRx20ins has been established with the approval of mobocertinib and amivantamab. There are also numerous novel targeted treatments for NSCLC with EGFRex20ins in development, which are anticipated to improve this patient population's survival even further. This review provides a reference for the clinical management of these patients by summarizing the most recent epidemiological, and clinicopathological characteristics, diagnostic techniques, and therapeutic advances of EGFRex20ins in NSCLC.
Insights
Epidermal growth factor receptor (EGFR) exon 20 insertions are a common mutation in non-small cell lung cancer (NSCLC). This review details recent advances in diagnosing and treating this challenging NSCLC subtype.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- EGFR exon 20 insertions (EGFRex20ins) represent 2-12% of EGFR mutations in non-small cell lung cancer (NSCLC).
- Most EGFRex20ins mutations occur in the loop structure, with A767_V769dup and S768_D770dup being the most frequent subtypes.
- NSCLC with EGFRex20ins typically shows resistance to standard EGFR tyrosine kinase inhibitors, chemotherapy, and immunotherapy.
Purpose of the Study:
- To provide a comprehensive overview of EGFRex20ins in NSCLC.
- To summarize current epidemiological, clinicopathological, diagnostic, and therapeutic information.
- To offer a reference for clinical management of patients with EGFRex20ins NSCLC.
Main Methods:
- Literature review of epidemiological data.
- Analysis of clinicopathological characteristics.
- Summary of diagnostic techniques and therapeutic advances.
Main Results:
- EGFRex20ins is the third most prevalent EGFR mutation in NSCLC.
- Specific subtypes like A767_V769dup and S768_D770dup are common.
- Approved treatments like mobocertinib and amivantamab offer new therapeutic options, with more in development.
Conclusions:
- EGFRex20ins presents unique challenges in NSCLC treatment due to resistance to conventional therapies.
- The development of targeted therapies, including mobocertinib and amivantamab, has improved treatment paradigms.
- Ongoing research into novel targeted treatments holds promise for further improving survival for NSCLC patients with EGFRex20ins.
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