The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
First-Line Gefitinib in Patients With Advanced Non–Small-Cell Lung Cancer Harboring Somatic EGFR Mutations
Abstract
PURPOSE: Somatic mutations in the epidermal growth factor receptor (EGFR) correlate with increased response in patients with non-small-cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). The multicenter iTARGET trial prospectively examined first-line gefitinib in advanced NSCLC patients harboring EGFR mutations and explored the significance of EGFR mutation subtypes and TKI resistance mechanisms. PATIENTS AND METHODS: Chemotherapy-naïve patients with advanced NSCLC with >or= 1 clinical characteristic associated with EGFR mutations underwent direct DNA sequencing of tumor tissue EGFR exons 18 to 21. Patients found to harbor any EGFR mutation were treated with gefitinib 250 mg/d until progression or unacceptable toxicity. The primary outcome was response rate. RESULTS: Ninety-eight patients underwent EGFR screening and mutations were detected in 34 (35%). EGFR mutations were primarily exon 19 deletions (53%) and L858R (26%) though 21% of mutation-positive cases had less common subtypes including exon 20 insertions, T790M/L858R, G719A, and L861Q. Thirty-one patients received gefitinib. The response rate was 55% (95% CI, 33 to 70) and median progression-free survival was 9.2 months (95% CI, 6.2 to 11.8). Therapy was well tolerated; 13% of patients had grade 3 toxicities including one grade 3 pneumonitis. Two patients with classic activating mutations exhibited de novo gefitinib resistance and had concurrent genetic anomalies usually associated with acquired TKI resistance, specifically the T790M EGFR mutation and MET amplification. CONCLUSION: First-line therapy with gefitinib administered in a genotype-directed fashion to patients with advanced NSCLC harboring EGFR mutations results in very favorable clinical outcomes with good tolerance. This strategy should be compared with combination chemotherapy, the current standard of care.
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“Most patients whose tumors harbor exon 19 deletions or L858R EGFR activating mutations have radiographic responses to monotherapy with the reversible adenosine triphosphate (ATP)-competitive EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib 17–23 and the irreversible EGFR TKI afatinib 24.”
From Structural, Biochemical, and Clinical Characterization of Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations in Lung Cancer (2013) · cites this paper as [17]
In the citing paper
“The discovery of EGFR mutations and the dramatic responses observed with EGFR TKIs in retrospective and small phase II studies [20, 61, 62] paved the way to a paradigm shift in the clinical trial design, favoring the development of clinically and then molecularly selected studies in NSCLC.”
From A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): Old successes and future perspectives (2015) · cites this paper as [20]
In the citing paper
“In this emerging era of targeted therapies, it is notable that most responses are not durable and that benefit is generally measured in months, not years.”
From Radiomics: Images Are More than Pictures, They Are Data (2016) · cites this paper as [16]
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Metadata
- Authors
- Sequist, L. V., Martins, R. G., Spigel, D., Grunberg, S. M., Spira, A., Jänne, P. A., Joshi, V. A., McCollum, D., Evans, T. L., Muzikansky, A., Kuhlmann, G. L., Han, M., Goldberg, J. S., Settleman, J., Iafrate, A. J., Engelman, J. A., Haber, D. A., Johnson, B. E., & Lynch, T. J.
- Affiliations
- Brigham and Women's Hospital (US)
- From the Massachusetts General Hospital Cancer Center; Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital; Department of Pathology, Massachusetts General Hospital; Department of Biostatistics, Massachusetts General Hospital, Boston; Harvard Medical School/Partners Health Care Center for Genetics and Genomics, Cambridge, MA; University of Washington, Seattle, WA; Sarah Cannon Research Institute, Nashville, TN; Fletcher Allen Health Care, Burlington, VT; Fairfax-Northern...
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2008-05-20
- Volume
- 26
- Issue
- 15
- Pages
- 2442-2449
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2101329867
- Cited by
- 820
- References
- 46
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 9 · 2023: 11 · 2022: 20 · 2021: 22 · 2020: 34 · 2019: 29 · 2018: 51 · 2017: 51 · 2016: 54 · 2015: 57 · 2014: 68 · 2013: 69 · 2012: 60
- FWCI
- 81.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical 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
- gefitinib, non-small cell lung cancer, EGFR mutation, first-line therapy, EGFR tyrosine kinase inhibitors, exon 19 deletion, L858R mutation, T790M mutation, MET amplification, progression-free survival, response rate, pneumonitis, genotype-directed therapy
- MeSH terms
- Gefitinib, Adenocarcinoma, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Neoplasm Staging, Prospective Studies, Quinazolines, Survival Rate, Central Nervous System Neoplasms, Treatment Outcome, In Situ Hybridization, Fluorescence, Carcinoma, Large Cell, Disease-Free Survival, ErbB Receptors
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