Uncommon mutation types of epidermal growth factor receptor and response to EGFR tyrosine kinase inhibitors in Chinese non-small cell lung cancer patients

Chen, Kaiyan; Yu, Xiaoqing; Wang, Haiyang; Huang, Zhiyu; Xu, Yanjun; Gong, Lei; Fan, Yun

doi:10.1007/s00280-017-3464-9

Cited by 31Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchLung Cancer Diagnosis and Treatment

Uncommon mutation types of epidermal growth factor receptor and response to EGFR tyrosine kinase inhibitors in Chinese non-small cell lung cancer patients

Chen, Kaiyan, Yu, Xiaoqing, Wang, Haiyang, Huang, Zhiyu, Xu, Yanjun, Gong, Lei, Fan, Yun·2017·Cancer Chemotherapy and Pharmacology

DOI 10.1007/s00280-017-3464-9

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Abstract

Purpose Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the standard therapy for advanced lung adenocarcinomas with common EGFR mutations. However, the efficacy of EGFR-TKIs in patients with uncommon EGFR mutations (other than exon 19 deletions or exon 21 L858R mutation) remains undetermined.Methods Seven hundred and fifty-five non-small cell lung cancer (NSCLC) patients with EGFR mutation analyses for TKI therapy were identified between October 2010 and December 2015 in East of China. And 66 patients bearing uncommon EGFR mutations were included to collect data from TKI response and prognosis. We categorised EGFR uncommon mutations as: sensitizing rare mutations (group 1: G719X, L861Q, S768I); Ex20 ins (group 2), or complex mutations (G719X + L861Q, G719X + S768I, 19 del + T790M, 19 del + L858R, L858R + S768I, and L858R + T790M; group 3).Results Of 66 patients given EGFR-TKI treatment, rare sensitive mutations, Ex20 ins, and complex mutations were identified in 37 (56.1%), 9 (13.6%), and 20 (33.3%) cases, respectively. TKI efficacy in patients harboring uncommon EGFR mutations exhibited a tumor response rate of 28.8% and a median progression-free survival (PFS) of 4.8 months. Additionally, patients with complex EGFR mutations had significantly longer PFS when compared with the remaining sensitizing rare mutations or Ex20 ins cases (8.6 vs. 4.1 vs. 3.1 months; p = 0.041). Importantly, complex EGFR mutations were independent predictors of increased overall survival (Hazard Ratios = 0.31; 95% confidence intervals: 0.11-0.90; p = 0.031). Among them, patients harboring Del-19 combined with L858R mutations showed a tendency to have higher response rate (RR) and improved PFS than those with other complex mutation patterns (RR: 66.7 vs. 14.3%, p = 0.021; PFS: 10.1 vs. 8.6 months, p = 0.232).Conclusions Personalized treatment should be evolving in different types of uncommon EGFR mutations. Clinical benefit from EGFR-TKIs was higher in NSCLC patients with complex EGFR mutations than those with other uncommon EGFR mutation types.

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Patients harboring exon 20 insertions have an ORR of 0-11% and a median PFS of 2-3 months when treated with first- or second-generation EGFR TKIs.
“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]”
From Heterogeneous Responses to Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) in Patients with Uncommon EGFR Mutations: New Insights and Future Perspectives in this Complex Clinical Scenario (2019) · cites this paper as [44]

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Authors: Chen, K., Yu, X., Wang, H., Huang, Z., Xu, Y., Gong, L., & Fan, Y.
Affiliations: Zhejiang Cancer Hospital (CN)
Zhejiang Chinese Medical University (CN)
Corresponding author: Fan, Yun
ORCID: Chen, Kaiyan
Yu, Xiaoqing
Wang, Haiyang
Huang, Zhiyu
Xu, Yanjun
Gong, Lei
Fan, Yun
Venue: Cancer Chemotherapy and Pharmacology
Publisher: Springer Science and Business Media LLC
Published: 2017-10-24
Volume: 80
Issue: 6
Pages: 1179-1187
ISSN: 0344-5704 (ISSN-L)
1432-0843
DOI: 10.1007/s00280-017-3464-9
OpenAlex: W2766513903
Cited by: 31
References: 37
Citations by year: 2024: 5 · 2023: 1 · 2022: 7 · 2021: 5 · 2020: 3 · 2019: 7 · 2018: 2
FWCI: 2.71
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (unspecified)
Locations: Cancer Chemotherapy and Pharmacology (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, EGFR tyrosine kinase inhibitors, non-small cell lung cancer, lung adenocarcinoma, exon 20 insertion, L858R, T790M, exon 19 deletion, G719X, S768I, L861Q, progression-free survival, overall survival
MeSH terms: Aged, Carcinoma, Non-Small-Cell Lung, China, Female, Humans, Lung Neoplasms, Male, Mutation, Protein Kinase Inhibitors, ErbB Receptors

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Uncommon mutation types of epidermal growth factor receptor and response to EGFR tyrosine kinase inhibitors in Chinese non-small cell lung cancer patients

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