The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Activity of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Patients with Non-small Cell Lung Cancer Harboring Rare Epidermal Growth Factor Receptor Mutations
Open accessAbstract
Introduction Mutations of the epidermal growth factor receptor (EGFR) have been proven to predict activity of the EGFR-tyrosine kinase inhibitors (EGFR-TKI), gefitinib and erlotinib. Although the "common" EGFR mutations, such as the L858R point mutation in exon 21 and the in-frame deletional mutation in exon 19, have been definitively associated with response to EGFR-TKIs, the correlation with response to treatment for many other rarer mutations is still unclear. In this study, we report the results of treating patients with advanced non-small cell lung cancer harboring rare EGFR mutations treated with EGFR-TKIs.Methods The frequency of rare mutations has been investigated in 681 cases of non-small cell lung cancer screened between 2006 and 2010. Mutations in exons 18 and 20, uncommon mutations in exons 19 and 21, and/or the presence of different mutations in a single tumor (complex mutations) were considered rare.Results EGFR mutations were detected in 99 tumors (14.5%). Eighteen cases carried rare mutations, and 10 of these patients were treated with erlotinib or gefitinib. The clinical outcome was described case by case with references to the literature. Of note, we found two EGFR mutations never identified before and one of unknown response to EGFR-TKIs.Conclusions Gefitinib and erlotinib have different antitumor activity according to the type of the EGFR mutation borne. Report of cases harboring rare mutations can support the decision-making process in this subset of patients.
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“The majority of exon 20 insertion mutations present a reduced affinity for EGFR-TKIs, although some insertion mutations have demonstrated prolonged periods of disease control with reversible EGFR-TKIs suggesting at least intermediate sensitivity, such as the insertion EGFR-A763_Y764insFQEA, which is highly sensitive to EGFR-TKIs in vitro.20 21”
From Mechanisms of resistance to EGFR-targeted drugs: lung cancer (2016) · cites this paper as [21]
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“lower overall response rate (ORR) (14–53%) in patients harboring G719X mutations, treated with first-generation EGFR TKIs [12,21,35,36]”
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“Other rarer mutations may be identified in the exon 21, but their sensitivity is generally low (L861R, L862V, V851X, A859X) or uncertain (E866K, H825L, P848L, H870Y/R, and G836S) [35,49,54,63]”
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The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP
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Erlotinib in Lung Cancer — Molecular and Clinical Predictors of Outcome
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Mutations of the Epidermal Growth Factor Receptor Gene in Lung Cancer
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Yang, J. C.-H., Sequist, L. V., Geater, S. L., Tsai, C.-M., Mok, T. S. K., Schuler, M., Yamamoto, N., Yu, C.-J., Ou, S.-H. I., Zhou, C., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00026-1 · Cited by 1,002
Mechanisms of resistance to EGFR-targeted drugs: lung cancer
Morgillo, F., Della Corte, C. M., Fasano, M., & Ciardiello, F. (2016) · ESMO Open · doi:10.1136/esmoopen-2016-000060 · Cited by 476
Chiu, C.-H., Yang, C.-T., Shih, J.-Y., Huang, M.-S., Su, W.-C., Lai, R.-S., Wang, C.-C., Hsiao, S.-H., Lin, Y.-C., Ho, C.-L., et al. (2015) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000504 · Cited by 241
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Metadata
- Authors
- De Pas, T., Toffalorio, F., Manzotti, M., Fumagalli, C., Spitaleri, G., Catania, C., Delmonte, A., Giovannini, M., Spaggiari, L., de Braud, F., & Barberis, M.
- Affiliations
- European Institute of Oncology (IT)
- University of Milan (IT)
- ORCID
- Venue
- Journal of Thoracic Oncology
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 6
- Issue
- 11
- Pages
- 1895-1901
- ISSN
- 1556-0864 (ISSN-L)
- OpenAlex
- W2005728761
- Cited by
- 138
- References
- 32
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 7 · 2022: 8 · 2021: 12 · 2020: 12 · 2019: 11 · 2018: 5 · 2017: 15 · 2016: 9 · 2015: 10 · 2014: 13 · 2013: 13 · 2012: 11
- FWCI
- 10.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thoracic Oncology (publishedVersion)
- PubMed (publishedVersion)
- 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
- epidermal growth factor receptor, EGFR mutation, uncommon EGFR mutations, EGFR tyrosine kinase inhibitors, gefitinib, erlotinib, non-small cell lung cancer, exon 18 mutations, exon 20 mutations, complex mutations, treatment response, predictive biomarkers
- MeSH terms
- Erlotinib Hydrochloride, Gefitinib, Adenocarcinoma, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Neoplasm Staging, Quinazolines, Retrospective Studies, Review Literature as Topic, Treatment Outcome, ErbB Receptors
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