CoChat
Sign Up
Cited by 35Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchLung Cancer Diagnosis and Treatment

Clinical characteristics and response to tyrosine kinase inhibitors of patients with non-small cell lung cancer harboring uncommon epidermal growth factor receptor mutations

Open access
Zhang, Yan, Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China, Wang, Zheng, Hao, Xuezhi, Hu, Xingsheng, Wang, Hongyu, Wang, Yan, Ying, Jianming +2 more·2017·Chinese Journal of Cancer Research
DOI 10.21147/j.issn.1000-9604.2017.01.03PMC PMC5348472
Open this paper in CoChat — free account

Abstract

Abstract Objective: To investigate the clinical features of patients with non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor (EGFR) mutations, and the treatment outcomes of EGFR tyrosine kinase inhibitors (TKIs) in these patients. Methods: We retrospectively analyzed the data of 128 NSCLC patients pathologically diagnosed with uncommon EGFR mutation in the Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and Beijing Hospital from January 2010 to December 2015, including 40 advanced patients who received EGFR-TKI. Results: Among the total 128 patients, 11 patients were non-adenocarcinoma, including squamous carcinoma (3.9%), adenosquamous carcinoma (2.3%), large cell carcinoma (0.8%), and composite neuroendocrine carcinoma (1.6%). Single mutations accounted for 75.0% (96/128), including G719X (29.7%), S768I (18.0%), 20 exon insertion (13.3%), L861Q (12.5%), De novo T790M (0.8%), and T725 (0.8%). Thirty-two patients harbored complex mutations. Forty advanced patients received EGFR-TKI, the objective response rate (ORR) was 20.0%, the disease control rate (DCR) was 85.0%, and the progression-free survival (PFS) was 6.4 [95% confidence interval (95% CI), 4.8−7.9] months. The exploratory analysis of tumor response and PFS in 33 patients with G719X/S768I/L861Q subtypes showed that ORR was 21.2% (7/33), the DCR was 93.9% (31/33), and PFS was 7.6 (95% CI, 5.8−9.4) months. Patients with exon 20 insertion mutation and De novo T790M experienced rapid disease progression with PFS no more than 2.7 months. Conclusions: Uncommon EGFR-mutant NSCLCs are heterogeneous, EGFR-TKIs can have different efficacy in this specific subtype, and thus further individual assessment is required for each case.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.21147/j.issn.1000-9604.2017.01.03

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 31 · Cited by 35

Research works printed but not linked: 23

  1. 1.Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30. doi: 10.3322/caac.21332. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  2. [2]Chen W, Zheng R, Zuo T, et al. National cancer incidence and mortality in China, 2012. Chin J Cancer Res. 2016;28:1–11. doi: 10.3978/j.issn.1000-9604.2016.02.08. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  3. [3]Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–57. doi: 10.1056/NEJMoa0810699. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  4. [4]Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010;11:121–8. doi: 10.1016/S1470-2045(09)70364-X. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  5. [5]Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011;12:735–42. doi: 10.1016/S1470-2045(11)70184-X. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  6. [6]Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13:239–46. doi: 10.1016/S1470-2045(11)70393-X. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  7. [7]Shi Y, Li J, Zhang S, et al. Molecular epidemiology of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology - Mainland China subset analysis of the PIONEER study. PLoS One. 2015;10:e0143515. doi: 10.1371/journal.pone.0143515. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  8. [8]Chiu CH, Yang CT, Shih JY, et al. Epidermal growth factor receptor tyrosine kinase inhibitor treatment response in advanced lung adenocarcinomas with G719X/L861Q/S768I mutations. J Thorac Oncol. 2015;10:793–9. doi: 10.1097/JTO.0000000000000504. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  9. [10]Kancha RK, von Bubnoff N, Peschel C, et al. Functional analysis of epidermal growth factor receptor (EGFR) mutations and potential implications for EGFR targeted therapy. Clin Cancer Res. 2009;15:460–7. doi: 10.1158/1078-0432.CCR-08-1757. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  10. [11]Wu JY, Yu CJ, Chang YC, et al. Effectiveness of tyrosine kinase inhibitors on “uncommon” epidermal growth factor receptor mutations of unknown clinical significance in non-small cell lung cancer. Clin Cancer Res. 2011;17:3812–21. doi: 10.1158/1078-0432.CCR-10-3408. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  11. [13]Beau-Faller M, Prim N, Ruppert AM, et al. Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10,117 patients: a multicentre observational study by the French ERMETIC-IFCT network. Ann Oncol. 2014;25:126–31. doi: 10.1093/annonc/mdt418. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  12. [15]Wu JY, Wu SG, Yang CH, et al. Lung cancer with epidermal growth factor receptor exon 20 mutations is associated with poor gefitinib treatment response. Clin Cancer Res. 2008;14:4877–82. doi: 10.1158/1078-0432.CCR-07-5123. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  13. [16]Yasuda H, Kobayashi S, Costa DB. EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications. Lancet Oncol. 2012;13:e23–31. doi: 10.1016/S1470-2045(11)70129-2. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  14. [17]Oxnard GR, Jänne PA. Power in numbers: meta-analysis to identify inhibitor-sensitive tumor genotypes. Clin Cancer Res. 2013;19:1634–6. doi: 10.1158/1078-0432.CCR-13-0169. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  15. [18]Masago K, Fujita S, Irisa K, et al. Good clinical response to gefitinib in a non-small cell lung cancer patient harboring a rare somatic epidermal growth factor gene point mutation; codon 768 AGC > ATC in exon 20 (S768I) Jpn J Clin Oncol. 2010;40:1105–9. doi: 10.1093/jjco/hyq087. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  16. [19]Ettinger DS, Wood DE, Akerley W, et al. NCCN Guidelines insights: non-small cell lung cancer, Version 4.2016. J Natl Compr Canc Netw. 2016;14:255–64. doi: 10.6004/jnccn.2016.0031. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  17. [20]Mitsudomi T, Yatabe Y. Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS J. 2010;277:301–8. doi: 10.1111/j.1742-4658.2009.07448.x. [DOI] [PubMed] [Google Scholar] · DOI
  18. [22]Hsieh MH, Fang YF, Chang WC, et al. Complex mutation patterns of epidermal growth factor receptor gene associated with variable responses to gefitinib treatment in patients with non-small cell lung cancer. Lung Cancer. 2006;53:311–22. doi: 10.1016/j.lungcan.2006.06.005. [DOI] [PubMed] [Google Scholar] · DOI
  19. [24]Yu HA, Arcila ME, Hellmann MD, et al. Poor response to erlotinib in patients with tumors containing baseline EGFR T790M mutations found by routine clinical molecular testing. Ann Oncol. 2014;25:423–8. doi: 10.1093/annonc/mdt573. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  20. [25]Peng L, Song ZG, Jiao SC. Efficacy analysis of tyrosine kinase inhibitors on rare non-small cell lung cancer patients harboring complex EGFR mutations. Sci Rep. 2014;4:6104. doi: 10.1038/srep06104. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  21. [26]Kobayashi S, Canepa HM, Bailey AS, et al. Compound EGFR mutations and response to EGFR tyrosine kinase inhibitors. J Thorac Oncol. 2013;8:45–51. doi: 10.1097/JTO.0b013e3182781e35. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  22. [27]Liu Y, Wu BQ, Zhong HH, et al. Screening for EGFR and KRAS mutations in non-small cell lung carcinomas using DNA extraction by hydrothermal pressure coupled with PCR-based direct sequencing. Int J Clin Exp Pathol. 2013;6:1880–9. [PMC free article] [PubMed] [Google Scholar]
  23. [28]Keam B, Kim DW, Park JH, et al. Rare and complex mutations of epidermal growth factor receptor, and efficacy of tyrosine kinase inhibitor in patients with non-small cell lung cancer. Int J Clin Oncol. 2014;19:594–600. doi: 10.1007/s10147-013-0602-1. [DOI] [PubMed] [Google Scholar] · DOI · Paper page

Authors
Zhang, Y., Department of Medical Oncology, N. C. C. H., Wang, Z., Hao, X., Hu, X., Wang, H., Wang, Y., Ying, J., Department of Pathology, B. H., & Department of Pathology, N. C. C. H.
Affiliations
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • Beijing Hospital (CN)
Corresponding author
Ying, Jianming
ORCID
Venue
Chinese Journal of Cancer Research
Publisher
Chinese Journal of Cancer Research
Published
2017
Volume
29
Issue
1
Pages
18-24
ISSN
1000-9604 (ISSN-L)
DOI
10.21147/j.issn.1000-9604.2017.01.03
PMC
PMC5348472
OpenAlex
W2591703692
Cited by
35
References
31
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 4
FWCI
4.07
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • Chinese Journal of Cancer Research (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • 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
non-small cell lung cancer, EGFR mutation, EGFR tyrosine kinase inhibitors, uncommon EGFR mutations, exon 20 insertion, T790M, complex mutations, treatment response, progression-free survival, molecular heterogeneity, targeted therapy resistance

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review