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Updated: Aug 21, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Targeting exon 20 insertion mutations in lung cancer
1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing, China.
Purpose Of Review:
The application of tyrosine kinase inhibitor (TKI) has successfully changed the standard of care in epidermal growth factor receptor ( EGFR ) positive non-small cell lung cancer. However, clinical survivals for patients with EGFR exon 20 insertions have failed to improve over the long period and the mutation appeared resistant to EGFR -TKIs. This overview focused on the current treatment strategies, summarized the emerging regimens for patients with EGFR exon 20 insertions, and demonstrated historical challenges and future development.
Recent Finding:
Current clinical trials suggested that several regimens selectively-targeted EGFR exon 20 insertions presented potent antitumor activity, like mobocertinib and the bispecific anti- EGFR-MET monoclonal antibody amivantamab and were approved by Food and Drug Administration (FDA) in patients progressed beyond first-line treatment. Novel treatments, including DZD9008, CLN-081, revealed modest clinical efficacy as well and clinical trials are underway, which may lead to improvement of survival outcomes.
Summary:
Recent clinical evidence indicates that targeted therapies could improve survival benefits to some extent. More efforts on drug development are underway to bring higher response rates both extracranial and intracranial, sustained clinical remission, and better survival benefits.
Insights
New targeted therapies show promise for non-small cell lung cancer patients with EGFR exon 20 insertions, offering improved survival outcomes. Ongoing research aims to further enhance treatment efficacy and patient benefits.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have advanced non-small cell lung cancer (NSCLC) care.
- EGFR exon 20 insertions confer resistance to traditional EGFR-TKIs, limiting survival improvements.
- This review addresses challenges and advancements in treating NSCLC with EGFR exon 20 insertions.
Approach:
- Summarizing current treatment strategies for EGFR exon 20 insertion mutations.
- Reviewing emerging targeted therapies and their clinical efficacy.
- Discussing historical treatment challenges and future directions in NSCLC therapy.
Key Points:
- Mobocertinib and amivantamab demonstrate potent antitumor activity against EGFR exon 20 insertions.
- These agents are FDA-approved for post-first-line treatment in advanced NSCLC.
- Novel agents like DZD9008 and CLN-081 show promise in ongoing clinical trials.
Conclusions:
- Targeted therapies offer incremental survival benefits for NSCLC patients with EGFR exon 20 insertions.
- Continued drug development is crucial for achieving higher response rates and sustained remission.
- Future research focuses on improving both extracranial and intracranial efficacy for better patient outcomes.
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