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A comprehensive review of uncommon EGFR mutations in patients with non-small cell lung cancer
Abstract
Introduction Patients with non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor (EGFR) mutations are a heterogeneous group exhibiting differential responses to EGFR inhibitors. This retrospective study reviews the prevalence of uncommon EGFR mutations in a Chinese NSCLC cohort and the clinical characteristics and efficacy of EGFR tyrosine kinase inhibitors (TKIs) associated with these patients.Materials andmethods A total of 5363 lung cancer patients were screened and underwent EGFR genotyping at the Guangdong Lung Cancer Institute. Of those with uncommon EGFR mutations, the clinical characteristics and responses to EGFR-TKIs were reviewed retrospectively.Results Uncommon EGFR mutations were observed in 218 patients, comprising 11.9% of all patients with documented EGFR mutations. More smokers (30.7% vs. 24.3%, P=0.039) and males (54.1% vs. 44.4%, P=0.007) were among the patients with uncommon mutations compared with common mutations. The most frequent uncommon mutations were exon 20 insertions (30.7%, n=67), followed by G719X mutations (21.1%, n=46) and compound L858R mutations (17.0%, n=37). Favorable efficacy was observed in patients harboring compound L858R or G719X mutations, with a median progression-free survival (PFS) of 15.2 (95% CI: 8.7-21.7) or 11.6 (95% CI: 3.6-19.6) months, respectively. The median PFS of those with the T790M mutation or an exon 20 insertion was 1.0 (95% CI: 0.0-2.2) and 3.0 (95% CI: 1.3-4.7) months, respectively.Conclusion This study reviewed the prevalence of uncommon EGFR mutations and their sensitivity to EGFR-TKIs. Favorable responses were observed in patients with G719X and compound L858R mutations, indicating that they may benefit from EGFR-TKIs as a first-line therapy.
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In the citing paper
“Uncommon Epidermal Growth Factor Receptor (EGFR) mutations represent a distinct and highly heterogeneous subgroup of Non-Small Cell Lung Cancers (NSCLCs), that accounts for approximately 10% of all EGFR-mutated patients.”
In the citing paper
“the sensitivity of uncommon mutations to first- and second-generation EGFR Tyrosine Kinase Inhibitors (TKIs) is widely heterogeneous and less well known”
In the citing paper
“Patients with uncommon mutations define a small and highly heterogeneous subgroup of patients with EGFR mutations, with different sensitivity to first- and second-generation EGFR TKIs”
In the citing paper
“G719X is the most frequently observed exon 18 mutation for incidence and the second most frequently observed uncommon mutation, after exon 20 insertions.”
In the citing paper
“Patients harboring exon 20 insertions are associated with an ORR of 0–11% and a median progression-free survival (PFS) of 2–3 months when treated with first- or second-generation EGFR TKIs [19,21,37,44,45,70]”
In the citing paper
“lower overall response rate (ORR) (14–53%) in patients harboring G719X mutations, treated with first-generation EGFR TKIs [12,21,35,36]”
In the citing paper
“However, the true incidence of these genetic events is unknown, with a reported frequency of 4–14% of all EGFR mutations [21,36,46,47].”
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Metadata
- Authors
- Tu, H.-Y., Ke, E.-E., Yang, J.-J., Sun, Y.-L., Yan, H.-H., Zheng, M.-Y., Bai, X.-Y., Wang, Z., Su, J., Chen, Z.-H., Zhang, X.-C., Dong, Z.-Y., Wu, S.-P., Jiang, B.-Y., Chen, H.-J., Wang, B.-C., Xu, C.-R., Zhou, Q., Mei, P., Luo, D.-L., Zhong, W.-Z., Yang, X.-N., & Wu, Y.-L.
- Affiliations
- Guangdong General Hospital (CN)
- Southern Medical University (CN)
- Corresponding author
- Wu, Yi-Long
- ORCID
- Venue
- Lung Cancer
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 114
- Pages
- 96-102
- ISSN
- 0169-5002 (ISSN-L)
- OpenAlex
- W2768053061
- Cited by
- 182
- References
- 30
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 13 · 2023: 19 · 2022: 30 · 2021: 25 · 2020: 42 · 2019: 26 · 2018: 13
- FWCI
- 18.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Lung Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hangzhou Science and Technology Bureau (2014Y2-00050, 201402031)
- National Health and Family Planning Commission of the People's Republic of China (2014Y2-00050, 201402031)
- National Key Research and Development Program of China (2014Y2-00050, 201402031)
- 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 mutation, non-small cell lung cancer, EGFR tyrosine kinase inhibitors, exon 20 insertion, G719X mutation, T790M mutation, progression-free survival, treatment response, smoking, Chinese patients
- MeSH terms
- Erlotinib Hydrochloride, Gefitinib, Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Exons, Female, Genotype, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Predictive Value of Tests, Quinazolines, Retrospective Studies, Smoking, Disease-Free Survival, Asian People, Protein Kinase Inhibitors, ErbB Receptors
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