CoChat
Sign Up
Cited by 37Lung Cancer Treatments and MutationsLung Cancer Diagnosis and TreatmentHER2/EGFR in Cancer Research

Uncommon EGFR mutations in a cohort of Chinese NSCLC patients and outcomes of first-line EGFR-TKIs and platinum-based chemotherapy

Open access
Shi, Jinpeng, Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai 200433, China, Yang, Hui, Jiang, Tao, Li, Xuefei, Zhao, Chao, Zhang, Limin, Zhao, Sha +9 more·2017·Chinese Journal of Cancer Research
DOI 10.21147/j.issn.1000-9604.2017.06.09PMC PMC5775013
Open this paper in CoChat — free account

Abstract

Abstract Objective: Data on the clinical activity of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung cancer (NSCLC) and uncommon EGFR mutations remain insufficient. This study aimed to investigate the effect of first-line EGFR-TKIs or platinum-based chemotherapy in NSCLC patients with uncommon EGFR mutations. Methods: We retrospectively enrolled 504 patients with EGFR-mutant NSCLC. The clinical characteristics and treatment outcomes were collected and compared between patients with common and uncommon EGFR-mutant NSCLC. Results: Seventy patients (13.9%) harboring uncommon EGFR mutations were included. Thirty of these patients received EGFR-TKIs and 40 received platinum-based chemotherapy as first-line therapy. The objective response rate (ORR) and median progression-free survival (mPFS) of patients treated with TKIs in the uncommon mutation group was significantly inferior to that in the common mutation group (ORR: 23.3% vs. 51.8%, P=0.003; mPFS: 7.1 vs. 10.9 months, P<0.001). In the uncommon group, mPFS was similar between first-line EGFR-TKIs treatment and platinum-based chemotherapy (7.1vs. 6.1 months, P=0.893). In patients with EGFR G719X or L861Q mutations, the mPFS was longer in the first-line EGFR-TKIs treatment group than in the chemotherapy group, but the difference was not statistically significant (G719X: 8.2 vs. 5.8 months, P=0.061; L861Q: 7.6 vs. 4.1 months, P=0.872). Multivariate analyses identified adenocarcinoma (P=0.003) as the independent predictive factor for PFS in patients with uncommon EGFR mutations who were treated with first-line EGFR-TKIs. Conclusions: The current study demonstrated that the effect of first-line EGFR-TKIs was similar to that of platinum-based chemotherapy in patients with uncommon EGFR-mutant NSCLC. Adenocarcinoma was the independent predictive factor for PFS in uncommon EGFR-mutant NSCLC patients treated with first-line EGFR-TKIs.

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.1000-9604.2017.06.09

Cites

7 of 7 references verified0 citation errors · 0 not checkable

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?

  • Clinical trial design and treatment of patients with atypical EGFR mutations often rely on mutated-exon location to predict treatment, although heterogeneity in drug sensitivity across a single exon has been observed.

    “Clinical trial design and treatment of patients with atypical EGFR mutations often rely on mutated-exon location to predict treatment, although heterogeneity in drug sensitivity across a single exon has been observed1,8,17.”

    From Structure-based classification predicts drug response in EGFR-mutant NSCLC (2021) · cites this paper as [17]

Self-check

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

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

Cites

Flagged first, then by citations

Research works printed but not linked: 38

  1. Chen W, Zheng R, Zuo T, et al. National cancer incidence and mortality in China, 2012. Chin J Cancer Res 2016;28:1-11. 1 .
  2. Chen Z, Fillmore CM, Hammerman PS, et al. Nonsmall-cell lung cancers: a heterogeneous set of diseases. Nat Rev Cancer 2014;14:535-46. 2 .
  3. Castellanos E, Feld E, Horn L. Driven by mutations: the predictive value of mutation subtype in EGFRmutated non-small cell lung cancer. J Thorac Oncol 2017;12:612-23. 3 .
  4. 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 l ung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011;12:735-42. 4 .
  5. Chan SK, Gullick WJ, Hill ME. Mutations of the epidermal growth factor receptor in non-small cell lung cancer - search and destroy. Eur J Cancer 2006;42:17-23. 5 .
  6. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361:947-57. 6 .
  7. Pallis AG, Voutsina A, Kalikaki A, et al. 'Classical' but not 'other' mutations of EGFR kinase domain are associated with clinical outcome in gefitinib-treated patients with non-small cell lung cancer. Br J Cancer 2007;97:1560-6. 7 .
  8. Shigematsu H, Lin L, Takahashi T, et al. Clinical and biological features associated with epidermal growth 8 . factor receptor gene mutations in lung cancers. J Natl Cancer Inst 2005;97:339-46.
  9. 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. 9 .
  10. Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362:2380-8. 10 .
  11. Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with nonsmall-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. 11 .
  12. Arcila ME, Nafa K, Chaft JE, et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther 2013;12:220-9. 12 .
  13. Beau-Faller M, Prim N, Ruppert AM, et al. Rare EGFR exon 18 and exon 20 mutations in non-smallcell lung cancer on 10 117 patients: a multicentre observational study by the French ERMETIC-IFCT network. Ann Oncol 2014;25:126-31. 13 .
  14. Sasaki H, Endo K, Takada M, et al. EGFR exon 20 insertion mutation in Japanese lung cancer. Lung Cancer 2007;58:324-8. 15 .
  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. 16 .
  16. Watanabe S, Minegishi Y, Yoshizawa H, et al. Effectiveness of gefitinib against non-small-cell lung cancer with the uncommon EGFR mutations G719X and L861Q. J Thorac Oncol 2014;9:189-94. 19 .
  17. Jiang T, Su C, Li X, et al. EGFR TKIs plus WBRT demonstrated no survival benefit other than that of TKIs alone in patients with NSCLC and EGFR mutation and brain metastases. J Thorac Oncol 2016;11:1718-28. 20 .
  18. Li X, Ren R, Ren S, et al. Peripheral blood for epidermal growth factor receptor mutation detection in non-small cell lung cancer patients. Transl Oncol 2014;7:341-8. 21 .
  19. Wu C, Zhao C, Yang Y, et al. High discrepancy of driver mutations in patients with NSCLC and synchronous multiple lung ground-glass nodules. J Thorac Oncol 2015;10:778-83. 22 .
  20. Zhao M, Zhang Y, Cai W, et al. The Bim deletion polymorphism clinical profile and its relation with tyrosine kinase inhibitor resistance in Chinese patients with non-small cell lung cancer. Cancer 2014;120:2299-307. 23 .
  21. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47. 24 .
  22. Wu YL, Zhou C, Liam CK, et al. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol 2015;26:1883-9. 26 .
  23. Li L, Zhang Z, Bie Z, et al. Epidermal growth factor receptor mutation analysis in cytological specimens and responsiveness to gefitinib in advanced non-small cell lung cancer patients. Chin J Cancer Res 2015;27:294-300. 27 .
  24. Zhou C, Wu YL, Chen G, et al. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol 2015;26:1877-83. 28 .
  25. Arrieta O, Cardona AF, Corrales L, et al. The impact of common and rare EGFR mutations in response to EGFR tyrosine kinase inhibitors and platinum-based chemotherapy in patients with non-small cell lung cancer. Lung Cancer 2015;87:169-75. 29 .
  26. 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. 31 .
  27. Lohinai Z, Hoda MA, Fabian K, et al. Distinct epidemiology and clinical consequence of classic versus rare EGFR mutations in lung adenocarcinoma. J Thorac Oncol 2015;10:738-46. 32 .
  28. Stone E, Allen HA, Saghaie T, et al. High proportion of rare and compound epidermal growth factor receptor mutations in an Australian population of non-squamous non-small-cell lung cancer. Intern Med J 2014;44:1188-92. 33 .
  29. 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. 34 .
  30. Zhang Y, Wang Z, Hao X, et al. Clinical characteristics and response to tyrosine kinase inhibitors of patients with non-small cell lung cancer harboring uncommon epidermal growth factor receptor mutations. Chin J Cancer Res 2017;29: 18-24. 35 .
  31. Cite this article as: Shi J, Yang H, Jiang T, Li X, Zhao C, Zhang L, Zhao S, Liu X, Jia Y, Wang Y, Xi L, Zhang S, Su C, Ren S, Zhou C. Uncommon EGFR mutations in a cohort of Chinese NSCLC patients and outcomes of first-line EGFRTKIs and platinum-based chemotherapy. Chin J Cancer Res 2017;29(6):543-552. doi: 10.21147/j.issn.1000-9604.2017.06.09
  32. 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. 37 .
  33. 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. 38 .
  34. 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. 39 .
  35. 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. 41 .
  36. 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. 42 .
  37. Yang CH, Yu CJ, Shih JY, et al. Specific EGFR mutations predict treatment outcome of stage IIIB/IV patients with chemotherapy-naive non-small-cell lung cancer receiving first-line gefitinib monotherapy. J Clin Oncol 2008;26:2745-53. 43 .
  38. Zhu X, Bai Q, Lu Y, et al. Response to tyrosine kinase inhibitors in lung adenocarcinoma with the rare epidermal growth factor receptor mutation S768I: a retrospective analysis and literature review. Target Oncol 2017;12:81-8. 44 .

Cited by

Sorted by citations

Authors
Shi, J., Department of Medical Oncology, S. P. H. &. T. C. I., Yang, H., Jiang, T., Li, X., Zhao, C., Zhang, L., Zhao, S., Liu, X., Jia, Y., Wang, Y., Xi, L., Zhang, S., Su, C., Ren, S., Zhou, C., & Department of Lung Cancer and Immunology, S. P. H.
Affiliations
Tongji University (CN)
ORCID
Venue
Chinese Journal of Cancer Research
Publisher
Chinese Journal of Cancer Research
Published
2017
Volume
29
Issue
6
Pages
543-552
ISSN
1000-9604 (ISSN-L)
DOI
10.21147/j.issn.1000-9604.2017.06.09
PMC
PMC5775013
OpenAlex
W2782686933
Cited by
37
References
7
Citations by year
2026: 1 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 9 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 1
FWCI
2.47
Type
journal article
Language
en
Open access
Locations
  • Chinese Journal of Cancer Research (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81402486, 81372392)
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 mutation, non-small cell lung cancer, EGFR tyrosine kinase inhibitors, platinum-based chemotherapy, first-line therapy, uncommon EGFR mutations, progression-free survival, objective response rate, adenocarcinoma, predictive factors, Chinese patients, treatment outcomes comparison, predictive biomarkers

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