EGFR tyrosine kinase inhibitor (TKI) in patients with advanced non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutations: A real-world study in China

Xu, Jianlin; Jin, Bo; Chu, Tianqing; Dong, Xue; Yang, Haitang; Zhang, Yanwei; Wu, Dan; Lou, Yuqing; Zhang, Xueyan; Wang, Huiming; Han, Baohui

doi:10.1016/j.lungcan.2016.01.018

Cited by 92Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchLung Cancer Diagnosis and Treatment

EGFR tyrosine kinase inhibitor (TKI) in patients with advanced non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutations: A real-world study in China

Xu, Jianlin, Jin, Bo, Chu, Tianqing, Dong, Xue, Yang, Haitang, Zhang, Yanwei, Wu, Dan, Lou, Yuqing +3 more·2016·Lung Cancer

DOI 10.1016/j.lungcan.2016.01.018

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Abstract

Introduction There are a number of uncommon EGFR mutations whose associations with TKIs are not well clarified. Here, we summarize the clinical data of patients with multiple uncommon EGFR mutations and their sensitivity to EGFR TKIs.Methods Between January 2009 and September 2014, we retrospectively examined stage IIIB/IV NSCLC patients harboring uncommon mutations in EGFR at the Shanghai Chest Hospital.Results A total of 123 NSCLC patients harboring uncommon EGFR mutations with treatment and survival details were included in this analysis. 95 Patients who received therapy that consisted of EGFR TKIs experienced a significantly improved overall survival (OS) compared with those who did not receive EGFR TKIs (18.96 months, 95% CI, 16.65-21.26 vs 12.22, 95% CI, 9.17-15.27, p=0.017). The median progression-free survival (PFS) for patients who harbored the L861Q, G719X, 20ins, Del-19+L858R, Del-19 or L858R+T790M, and the Del-19 or L858R+other mutations were 8.90 months (95% CI, 4.47-13.34), 5.98 months (95% CI, 1.53-10.42), 2.00 months (95% CI, 0.00-5.41), 9.53 months (95% CI, 0.00-19.41), 1.94 months (95% CI, 0.00-4.43), and 9.79 months (95% CI, 0.73-18.85), respectively. The best objective response rates (ORRs) for patients who harbored L861Q, G719X, 20ins, Del-19+L858R, Del-19 or L858R+T790M, Del-19 or L858R+others were 46.7%, 42.9%, 8.3%, 71.4%, 22.2%, and 55.6%, respectively.Conclusions These results suggest that EGFR TKI therapy is effective in patients with L861Q/G719X/Del-19+L858R/Del-19 or L858R+other mutations; less effective in patients with 20ins/Del-19 or L858R+T790M.

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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 [45]
Patients with complex mutations containing exon 19 deletions or exon 21 L858R point mutations are associated with a more favorable outcome than those containing rare mutations only, with the best objective rates seen in double exon 19 deletions/L858R.
“clinical evidence suggesting that patients with complex mutations containing exon 19 deletions or exon 21 L858R point mutations are associated with a more favorable outcome than those containing rare mutations only [22,43,47,91], with the best objective rates seen in double exon 19 deletions/L858R [45].”
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 [45]
De novo T790M mutations are observed in approximately 3% of all EGFR-mutated NSCLC patients with standard methods and are associated with reduced sensitivity to first- or second-generation EGFR TKIs, with an ORR of 14-33% and a median PFS of 1.94-2.9 months.
“De novo T790M mutations constitute a small subgroup of EGFR mutations, which are observed in approximately 3% of all EGFR-mutated NSCLC patients with standard methods [92], and are generally associated with reduced sensitivity to first- or second-generation EGFR TKIs, with an ORR of 14–33% and a median PFS of 1.94–2.9 months [37,45,91].”
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 [45]

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Authors: Xu, J., Jin, B., Chu, T., Dong, X., Yang, H., Zhang, Y., Wu, D., Lou, Y., Zhang, X., Wang, H., & Han, B.
Affiliations: Shanghai Jiao Tong University (CN)
Corresponding author: Han, Baohui
ORCID: Xu, Jianlin
Jin, Bo
Chu, Tianqing
Dong, Xue
Yang, Haitang
Zhang, Yanwei
Wu, Dan
Lou, Yuqing
Zhang, Xueyan
Wang, Huiming
Han, Baohui
Venue: Lung Cancer
Publisher: Elsevier BV
Published: 2016-06
Volume: 96
Pages: 87-92
ISSN: 0169-5002 (ISSN-L)
DOI: 10.1016/j.lungcan.2016.01.018
OpenAlex: W2255412755
Cited by: 92
References: 34
Citations by year: 2025: 7 · 2024: 6 · 2023: 10 · 2022: 17 · 2021: 6 · 2020: 14 · 2019: 12 · 2018: 7 · 2017: 10 · 2016: 2
FWCI: 9.26
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Lung Cancer (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: EGFR tyrosine kinase inhibitors, advanced non-small cell lung cancer, uncommon EGFR mutations, L858R mutation, T790M mutation, overall survival, progression-free survival, objective response rate, real-world evidence, treatment sensitivity, China
MeSH terms: Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, China, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Neoplasm Staging, Retrospective Studies, Treatment Outcome, Disease-Free Survival, Protein Kinase Inhibitors, ErbB Receptors

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EGFR tyrosine kinase inhibitor (TKI) in patients with advanced non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutations: A real-world study in China

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