Clinical efficacy of first-generation EGFR-TKIs in patients with advanced non-small-cell lung cancer harboring EGFR exon 20 mutations
Open accessAbstract
PURPOSE: Subsets of non-small-cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations carry uncommon subtypes. We evaluated the efficacy of first-generation EGFR-tyrosine kinase inhibitors (TKIs; erlotinib, gefitinib, and icotinib) in patients with non-small-cell lung cancer carrying insertions and T790M and S768I mutations in EGFR exon 20. PATIENTS AND METHODS: Patients carrying EGFR exon 20 insertion/T790M/S768I mutations and treated with EGFR-TKIs were evaluated from 2005 to 2014 in Zhejiang Cancer Hospital. The efficacy was evaluated using the Kaplan-Meier method and compared with the log-rank test. RESULTS: Sixty-two patients with exon 20 insertion/T790M/S768I mutations were enrolled. Mutations including exon 20 insertions and T790M and S768I mutations were observed in 29, 23, and ten patients, respectively. In total, the response rate and median progression-free survival (PFS) were 8.1% and 2.1 months, respectively. Patients with S768I mutation manifested the longest median PFS (2.7 months), followed by those with T790M (2.4 months) and exon 20 insertions (1.9 months; P=0.022). Patients with complex mutations show a better PFS than those with single mutations (2.7 months vs 1.9 months; P=0.034). CONCLUSION: First-generation EGFR-TKIs are less effective in patients with exon 20 uncommon mutations than in those with common mutations. Patients with complex mutations benefited more from first-generation EGFR-TKIs than those with single mutations.
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Most exon 20 insertion mutations, except the rare A763_Y764insFQEA, make tumors resistant to the standard first-line EGFR inhibitors erlotinib, gefitinib, and afatinib.
“EGFR Ex20Ins tumors are generally unresponsive to 1st and 2nd generation EGFR inhibitors”
From Antitumor Activity of Osimertinib, an Irreversible Mutant-Selective EGFR Tyrosine Kinase Inhibitor, in NSCLC Harboring EGFR Exon 20 Insertions (2018) · cites this paper as [5]
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- Authors
- Cheng, G., Song, Z., & Chen, D.
- Affiliations
- Zhejiang Cancer Hospital (CN)
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Corresponding author
- Cheng, Guoping
- Song, Zhengbo
- Venue
- OncoTargets and Therapy
- Publisher
- Informa UK Limited
- Published
- 2016-07
- Volume
- Volume 9
- Pages
- 4181-4186
- ISSN
- 1178-6930 (ISSN-L)
- PMC
- PMC4944908
- OpenAlex
- W2461029491
- Cited by
- 77
- References
- 26
- Citations by year
- 2025: 8 · 2024: 10 · 2023: 8 · 2022: 7 · 2021: 8 · 2020: 13 · 2019: 7 · 2018: 6 · 2017: 9 · 2016: 1
- FWCI
- 6.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- OncoTargets and Therapy (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- EGFR exon 20 insertion, T790M mutation, advanced non-small cell lung cancer, erlotinib, gefitinib, icotinib, progression-free survival, treatment response
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