Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor-sensitive Exon 19 Insertion and Exon 20 Insertion in Patients With Advanced Non–Small-cell Lung Cancer
Abstract
Background The clinical responsiveness to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients with exon 19 insertion and the specific exon 20 insertion (A763_Y764 insFQEA) are still not well known.Materials and methods We analyzed cancer specimens taken from NSCLC patients for EGFR mutations using RNA reverse transcription polymerase chain reaction or direct DNA sequencing. The clinical course and responsiveness to an EGFR TKI in patients with EGFR exon 19 insertion or exon 20 insertion (A763_Y764 insFQEA) were recorded. The published data regarding these mutations were also reviewed.Results From September 1995 to May 2015, we found 4 patients with an EGFR exon 19 insertion and 6 patients with an EGFR exon 20 insertion (A763_Y764 insFQEA) at the National Taiwan University Hospital. Among patients with an exon 19 insertion, 3 received an EGFR TKI. Of the 3 patients, 1 had a partial response, 1 had stable disease, and 1 had progressive disease. Of the 6 patients with the exon 20 insertion (A763_Y764 insFQEA), 3 received an EGFR TKI. Of those 3 patients, 2 had a partial response and 1 had progressive disease. A review of the published data, together with the data from our patients, patients with an exon 19 insertion and treated with an EGFR TKI (n = 18) had a response rate of 56% and a median time to progression of 10.4 months. Patients with the exon 20 insertion (A763_Y764 insFQEA) and treated with an EGFR TKI (n = 11) had a response rate of 73% and a median time to progression of 5.0 months.Conclusions Advanced NSCLC bearing the EGFR exon 19 insertion or exon 20 insertion (A763_Y764 insFQEA) is sensitive to EGFR TKIs.
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Exon 19 insertions are associated with in vitro and in vivo sensitivity to first-/second-generation EGFR TKIs, although ORR may be slightly lower (about 40-50%) than with classic mutations.
“These insertions exhibit structural similarities with exon 19 deletions and have been associated with in vitro and in vivo sensitivity to first-/second-generation EGFR TKIs [60], although the ORR may be slightly lower (about 40–50%) than reported with classic mutations [61,62]”
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- Authors
- Lin, Y.-T., Liu, Y.-N., Wu, S.-G., Yang, J. C.-H., & Shih, J.-Y.
- Affiliations
- National Taiwan University Hospital (TW)
- National Taiwan University (TW)
- Corresponding author
- Shih, Jin-Yuan
- Venue
- Clinical Lung Cancer
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 18
- Issue
- 3
- Pages
- 324-332.e1
- ISSN
- 1525-7304 (ISSN-L)
- OpenAlex
- W2561330651
- Cited by
- 43
- References
- 40
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 10 · 2019: 5 · 2018: 7 · 2017: 1 · 2014: 1
- FWCI
- 3.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Lung Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Health and Welfare (MOHW103-TDU-PB-211-144002)
- National Taiwan University (103R7601-3)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- EGFR tyrosine kinase inhibitors, EGFR exon 20 insertion, non-small cell lung cancer, EGFR mutation, treatment response, time to progression, advanced non-small cell lung cancer
- MeSH terms
- Erlotinib Hydrochloride, Aged, Carcinoma, Non-Small-Cell Lung, Drug Resistance, Exons, Female, Humans, Lung Neoplasms, Male, Middle Aged, Neoplasm Staging, Taiwan, Mutagenesis, Insertional, Genes, erbB-1, Protein Kinase Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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