Lung Cancer with Epidermal Growth Factor Receptor Exon 20 Mutations Is Associated with Poor Gefitinib Treatment Response

Wu, Jenn-Yu; Wu, Shang-Gin; Yang, Chih-Hsin; Gow, Chien-Hung; Chang, Yih-Leong; Yu, Chong-Jen; Shih, Jin-Yuan; Yang, Pan-Chyr

doi:10.1158/1078-0432.ccr-07-5123

Cited by 319Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchLung Cancer Diagnosis and Treatment

Lung Cancer with Epidermal Growth Factor Receptor Exon 20 Mutations Is Associated with Poor Gefitinib Treatment Response

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Wu, Jenn-Yu, Wu, Shang-Gin, Yang, Chih-Hsin, Gow, Chien-Hung, Chang, Yih-Leong, Yu, Chong-Jen, Shih, Jin-Yuan, Yang, Pan-Chyr·2008·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-07-5123

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Abstract

Purpose: Clinical reports about responsiveness to gefitinib treatment in patients of non-small cell lung cancer (NSCLC) with mutations in exon 20 of epidermal growth factor receptor (EGFR) are limited. To increase understanding of the influence of exon 20 mutations on NSCLC treatment with gefitinib, we investigated the clinical features of lung cancer in patients with exon 20 mutations and analyzed the gefitinib treatment response. Experimental Design: We surveyed the clinical data and mutational studies of NSCLC patients with EGFR exon 20 mutations in the National Taiwan University Hospital and reviewed the literature reports about EGFR exon 20 mutations and the gefitinib treatment response. Results: Twenty-three patients with mutations in exon 20 were identified. Nine (39%) had coexisting mutations in EGFR exons other than exon 20. Sixteen patients received gefitinib treatment, and a response was noted in 4 patients. The gefitinib response rate of NSCLC with exon 20 mutations was 25%, far lower than those with deletions in exon 19 and L858R mutations. Interestingly, different exon 20 mutations and coexisting mutations seemed to have a different influence on gefitinib response. Conclusions: EGFR exon 20 mutations of NSCLC patients result in poorer responsiveness to gefitinib treatment, but variability exists between different individuals.

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Several studies have shown that 1G EGFR-TKI are less effective in patients with NSCLC harboring uncommon EGFR mutations compared with patients harboring common EGFR mutations.
“Several studies, although very small, have shown that 1G EGFR‐TKI are less effective in patients with NSCLC harboring such uncommon EGFR mutations, compared with patients harboring common EGFR mutations.”
From Sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors of uncommon epidermal growth factor receptor mutations L861Q and S768I: What is the optimal epidermal growth factor receptor‐tyrosine kinase inhibitor? (2016) · cites this paper as [18]
Many studies have shown that uncommon EGFR mutations are less sensitive to 1G EGFR-TKIs (objective response rate less than 50%) compared with common EGFR mutations.
“many studies have shown that these uncommon EGFR mutations were less sensitive to 1G EGFR‐TKI (objective response rate, less than 50%), compared with common EGFR mutations.18, 19, 20, 21, 22, 23, 24, 25, 26”
From Sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors of uncommon epidermal growth factor receptor mutations L861Q and S768I: What is the optimal epidermal growth factor receptor‐tyrosine kinase inhibitor? (2016) · cites this paper as [18]
Considering these findings, afatinib might be optimal for patients with NSCLC harboring EGFR uncommon mutations including exon 18 mutations, L861Q and S768I in clinical settings.
“Considering these findings including our studies, 18, 19, 20, 21, 22, 23, 27, 28, 41 afatinib might be optimal for patients with NSCLC harboring the EGFR uncommon mutations including exon 18 mutations, L861Q and S768I in clinical settings.”
From Sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors of uncommon epidermal growth factor receptor mutations L861Q and S768I: What is the optimal epidermal growth factor receptor‐tyrosine kinase inhibitor? (2016) · cites this paper as [18]

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Authors: Wu, J.-Y., Wu, S.-G., Yang, C.-H., Gow, C.-H., Chang, Y.-L., Yu, C.-J., Shih, J.-Y., & Yang, P.-C.
Affiliations: 1Internal Medicine, Departments of
2Oncology, and
Luodong Poh-Ai Hospital (TW)
National Taiwan University Hospital (TW)
ORCID: Wu, Shang-Gin
Gow, Chien-Hung
Chang, Yih-Leong
Yu, Chong-Jen
Shih, Jin-Yuan
Yang, Pan-Chyr
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2008-08-01
Volume: 14
Issue: 15
Pages: 4877-4882
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-07-5123
OpenAlex: W2048733384
Cited by: 319
References: 47
Citations by year: 2026: 5 · 2025: 8 · 2024: 11 · 2023: 18 · 2022: 15 · 2021: 12 · 2020: 15 · 2019: 11 · 2018: 13 · 2017: 21 · 2016: 19 · 2015: 27 · 2014: 25 · 2013: 36 · 2012: 26
FWCI: 17.44
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Council (NSC-95-2314-B-002-113-MY3)
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 exon 20 mutations, non-small cell lung cancer, gefitinib, treatment response, EGFR tyrosine kinase inhibitors, exon 19 deletion, L858R mutation, predictive biomarkers
MeSH terms: Gefitinib, Aged, Aged, 80 and over, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Exons, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Quinazolines, Treatment Outcome, Drug Resistance, Neoplasm, ErbB Receptors

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Lung Cancer with Epidermal Growth Factor Receptor Exon 20 Mutations Is Associated with Poor Gefitinib Treatment Response

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