Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
March-2025 Volume 29 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-2025 Volume 29 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Patients with non‑small cell lung cancer with the exon 21 L858R mutation: From distinct mechanisms to epidermal growth factor receptor tyrosine kinase inhibitor treatments (Review)

  • Authors:
    • Jia-Yu Liu
    • Shou-Zheng Wang
    • Han-Qi Yuan
    • Jun-Ling Li
    • Pu-Yuan Xing
  • View Affiliations / Copyright

    Affiliations: Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China, Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing 101125, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 109
    |
    Published online on: December 20, 2024
       https://doi.org/10.3892/ol.2024.14855
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The most common oncogenic driver in non‑small cell lung cancer (NSCLC) is epidermal growth factor receptor (EGFR) gene mutations, which are more common in Asian (30‑50%) than in Caucasian (10‑15%) populations. Exon 19 deletion (ex19del) and exon 21 L858R (ex21 L858R) mutations account for ~45 and 40% of all EGFR mutations, respectively. Moreover, EGFR‑tyrosine kinase inhibitors (TKIs) may be more effective and improve the quality of life of patients with NSCLC more than chemotherapy regimens. By contrast, patients with the ex21 L858R mutation may have a lower sensitivity and duration of response to EGFR‑TKIs as well as a shorter survival compared with those with the ex19del mutation. However, current guidelines classify ex21 L858R and ex19del as the same condition and recommend the same treatment strategy for both. Aiming for precision medicine, the present review introduces and compares different EGFR‑TKIs for the ex21 L858R mutation to assess more personalized treatment options for the population with this mutation.
View Figures

Figure 1

View References

1 

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global Cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI

2 

Zheng R, Zhang S, Zeng H, Wang S, Sun K, Chen R, Li L, Wei W and He J: Cancer incidence and mortality in China, 2016. J Natl Cancer Cent. 2:1–9. 2022. View Article : Google Scholar : PubMed/NCBI

3 

Duma N, Santana-Davila R and Molina JR: Non-Small cell lung cancer: Epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc. 94:1623–1640. 2019. View Article : Google Scholar : PubMed/NCBI

4 

Nan X, Xie C, Yu X and Liu J: EGFR TKI as First-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer. Oncotarget. 8:75712–75726. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Yang CY, Yang JC and Yang PC: Precision management of advanced Non-small cell lung cancer. Annu Rev Med. 71:117–136. 2020. View Article : Google Scholar : PubMed/NCBI

6 

Mitchell RA, Luwor RB and Burgess AW: Epidermal growth factor receptor: Structure-function informing the design of anticancer therapeutics. Exp Cell Res. 371:1–19. 2018. View Article : Google Scholar : PubMed/NCBI

7 

Hellyer JA, White MN, Gardner RM, Cunanan K, Padda SK, Das M, Ramchandran K, Neal JW and Wakelee HA: Impact of tumor suppressor gene Co-mutations on differential response to EGFR TKI therapy in EGFR L858R and exon 19 deletion lung cancer. Clin Lung Cancer. 23:264–272. 2022. View Article : Google Scholar : PubMed/NCBI

8 

Hong W, Wu Q, Zhang J and Zhou Y: Prognostic value of EGFR 19-del and 21-L858R mutations in patients with non-small cell lung cancer. Oncol Lett. 18:3887–3895. 2019.PubMed/NCBI

9 

Tsai MF, Chang TH, Wu SG, Yang HY, Hsu YC, Yang PC and Shih JY: EGFR-L858R mutant enhances lung adenocarcinoma cell invasive ability and promotes malignant pleural effusion formation through activation of the CXCL12-CXCR4 pathway. Sci Rep. 5:135742015. View Article : Google Scholar : PubMed/NCBI

10 

Wang T, Zheng L, Wang Q and Xiao S: Single-cell analyses reveal tumor microenvironment differences between EGFR 19del and L858R mutations in lung adenocarcinoma. J Thorac Oncol. 17 (Suppl):S6062022. View Article : Google Scholar

11 

Rossi A and Mari E: EGFR-Mutant Non-small cell lung cancer: State-of-the-Art and future perspectives. EMJ. 7:112–122. 2022.

12 

Abourehab MAS, Alqahtani AM, Youssif BGM and Gouda AM: Globally approved EGFR inhibitors: Insights into their syntheses, target kinases, biological activities, receptor interactions, and metabolism. Molecules. 26:66772021. View Article : Google Scholar : PubMed/NCBI

13 

Amelia T, Kartasasmita RE, Ohwada T and Tjahjono DH: Structural insight and development of EGFR tyrosine kinase inhibitors. Molecules. 27:8192022. View Article : Google Scholar : PubMed/NCBI

14 

Girard N: Optimizing outcomes in EGFR mutation-positive NSCLC: Which tyrosine kinase inhibitor and when? Future Oncol. 14:1117–1132. 2018. View Article : Google Scholar : PubMed/NCBI

15 

Fukuoka M, Wu YL, Thongprasert S, Sunpaweravong P, Leong SS, Sriuranpong V, Chao TY, Nakagawa K, Chu DT, Saijo N, et al: Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 29:2866–2874. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, 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. 26:1883–1889. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, 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. 13:239–246. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Shi YK, Wang L, Han BH, Li W, Yu P, Liu YP, Ding CM, Song X, Ma ZY, Ren XL, et al: First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): A phase 3, open-label, randomized study. Ann Oncol. 28:2443–2450. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Li X, Zhang L, Jiang D, Wang Y, Zang A, Ding C, Zhao M, Su W, Zhang Y, Zhong D, et al: Routine-dose and High-dose icotinib in patients with advanced Non-small cell lung cancer harboring EGFR Exon 21-L858R mutation: The randomized, phase II, INCREASE trial. Clin Cancer Res. 26:3162–3171. 2020. View Article : Google Scholar : PubMed/NCBI

20 

Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, et al: Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 31:3327–3334. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, et al: Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): An open-label, randomised phase 3 trial. Lancet Oncol. 15:213–222. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, et al: Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): Analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 16:141–151. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, et al: Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): A phase 2B, open-label, randomised controlled trial. Lancet Oncol. 17:577–589. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Paz-Ares L, Tan EH, O'Byrne K, Zhang L, Hirsh V, Boyer M, Yang JC, Mok T, Lee KH, Lu S, et al: Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: Overall survival data from the phase IIb LUX-Lung 7 trial. Ann Oncol. 28:270–277. 2017. View Article : Google Scholar : PubMed/NCBI

25 

Lau SC, Chooback N, Ho C and Melosky B: Outcome differences between First- and Second-generation EGFR inhibitors in advanced EGFR mutated NSCLC in a large Population-based cohort. Clin Lung Cancer. 20:e576–e583. 2019. View Article : Google Scholar : PubMed/NCBI

26 

Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, et al: Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): A randomised, open-label, phase 3 trial. Lancet Oncol. 18:1454–1466. 2017. View Article : Google Scholar : PubMed/NCBI

27 

Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Lee M, Linke R, Rosell R, Corral J, et al: Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non-small-cell lung cancer and EGFR-Activating mutations. J Clin Oncol. 36:2244–2250. 2018. View Article : Google Scholar : PubMed/NCBI

28 

Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Chawla A, Rosell R, Corral J, Migliorino MR, et al: Updated overall survival in a randomized study comparing dacomitinib with gefitinib as First-line treatment in patients with advanced Non-Small-cell lung cancer and EGFR-activating mutations. Drugs. 81:257–266. 2021. View Article : Google Scholar : PubMed/NCBI

29 

Cheng Y, Mok TS, Zhou X, Lu S, Zhou Q, Zhou J, Du Y, Yu P, Liu X, Hu C, et al: Safety and efficacy of first-line dacomitinib in Asian patients with EGFR mutation-positive non-small cell lung cancer: Results from a randomized, open-label, phase 3 trial (ARCHER 1050). Lung Cancer. 154:176–185. 2021. View Article : Google Scholar : PubMed/NCBI

30 

Pluzanski A, Wu Y, Cheng Y, Zhou X, Migliorino MR, Niho S, Nakagawa K, Lee KH, Corral J, Rosell R, et al: Safety and efficacy of first-line dacomitinib in advanced non-small cell lung cancer by EGFR mutation subtype in ARCHER 1050. J Thorac Oncol. 16 (Suppl):S617–S618. 2021. View Article : Google Scholar

31 

Tanaka H, Sakamoto H, Akita T, Ohyanagi F, Kawashima Y, Tambo Y, Tanimoto A, Horiike A, Miyauchi E, Tsuchiya-Kawano Y, et al: Clinical efficacy of dacomitinib in rechallenge setting for patients with epidermal growth factor receptor mutant non-small cell lung cancer: A multicenter retrospective analysis (TOPGAN2020-02). Thorac Cancer. 13:1471–1478. 2022. View Article : Google Scholar : PubMed/NCBI

32 

Wang S, Wang Y, Wang L, Liu Y, Hu Y, Liu Z, Yao Y, Liang L, Liu J, Li J, et al: Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) 21L858R mutation: A multicenter, ambispective, consecutive case-series study. Ann Oncol. 34 (Suppl):S16972023. View Article : Google Scholar

33 

Cho BC, Felip E, Spira AI, Girard N, Lee JS, Lee SH, Ostapenko YV, Danchaivijitr P, Liu B, Alip A, et al: Amivantamab plus lazertinib vs osimertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results from MARIPOSA, a phase III, global, randomized, controlled trial. Ann Oncol. 34 (Suppl):S13062023. View Article : Google Scholar

34 

Ke EE, Zhou Q, Zhang QY, Su J, Chen ZH, Zhang XC, Xu CR, Yang JJ, Tu HY, Yan HH, et al: A higher proportion of the EGFR T790M mutation may contribute to the better survival of patients with exon 19 deletions compared with those with L858R. J Thorac Oncol. 12:1368–1375. 2017. View Article : Google Scholar : PubMed/NCBI

35 

Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ, Orme JP, Finlay MR, Ward RA, Mellor MJ, et al: AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 4:1046–1061. 2014. View Article : Google Scholar : PubMed/NCBI

36 

Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, et al: Osimertinib in untreated EGFR-Mutated advanced non-small-cell lung cancer. N Engl J Med. 378:113–125. 2018. View Article : Google Scholar : PubMed/NCBI

37 

Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, et al: Overall survival with osimertinib in untreated, EGFR-Mutated advanced NSCLC. N Engl J Med. 382:41–50. 2020. View Article : Google Scholar : PubMed/NCBI

38 

Lu S, Dong X, Jian H, Chen J, Chen G, Sun Y, Ji Y, Wang Z, Shi J, Lu J, et al: AENEAS: A randomized phase III trial of aumolertinib versus gefitinib as First-Line therapy for Locally Advanced or MetastaticNon-Small-Cell lung cancer with EGFR exon 19 deletion or L858R mutations. J Clin Oncol. 40:3162–3171. 2022. View Article : Google Scholar : PubMed/NCBI

39 

Sakata Y, Sakata S, Oya Y, Tamiya M, Suzuki H, Shibaki R, Okada A, Kobe H, Matsumoto H, Yokoi T, et al: Osimertinib as first-line treatment for advanced epidermal growth factor receptor mutation-positive non-small-cell lung cancer in a real-world setting (OSI-FACT). Eur J Cancer. 159:144–153. 2021. View Article : Google Scholar : PubMed/NCBI

40 

Ito K, Morise M, Wakuda K, Hataji O, Shimokawaji T, Takahashi K, Furuya N, Takeyama Y, Goto Y, Abe T, et al: A multicenter cohort study of osimertinib compared with afatinib as first-line treatment for EGFR-mutated non-small-cell lung cancer from practical dataset: CJLSG1903. ESMO Open. 6:1001152021. View Article : Google Scholar : PubMed/NCBI

41 

Gijtenbeek RGP, Damhuis RAM, van der Wekken AJ, Hendriks LEL, Groen HJM and van Geffen WH: Overall survival in advanced epidermal growth factor receptor mutated non-small cell lung cancer using different tyrosine kinase inhibitors in The Netherlands: a retrospective, nationwide registry study. Lancet Reg Health Eur. 27:1005922023. View Article : Google Scholar : PubMed/NCBI

42 

Lu X, Yu L, Zhang Z, Ren X, Smaill JB and Ding K: Targeting EGFR(L858R/T790M) and EGFR(L858R/T790M/C797S) resistance mutations in NSCLC: Current developments in medicinal chemistry. Med Res Rev. 38:1550–1581. 2018. View Article : Google Scholar : PubMed/NCBI

43 

Shum E, Elamin YY, Piotrowska Z, Spigel DR, Reckamp KL, Rotow JK, Tan DSW, Lim SM, Kim TM, Lin CC, et al: A phase 1/2 study of BLU-945 in patients with common activating EGFR-mutant non-small cell lung cancer (NSCLC): SYMPHONY trial in progress. J Clin Oncol. 40:TPS91562022. View Article : Google Scholar

44 

Wang S, Song Y and Liu D: EAI045: The fourth-generation EGFR inhibitor overcoming T790M and C797S resistance. Cancer Lett. 385:51–54. 2017. View Article : Google Scholar : PubMed/NCBI

45 

Takeda M, Okamoto I and Nakagawa K: Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer. Lung Cancer. 88:74–79. 2015. View Article : Google Scholar : PubMed/NCBI

46 

Díaz-Serrano A, Gella P, Jiménez E, Zugazagoitia J and Paz-Ares Rodríguez L: Targeting EGFR in lung cancer: Current standards and developments. Drugs. 78:893–911. 2018. View Article : Google Scholar : PubMed/NCBI

47 

Wang L, Li Y, Li L, Wu Z, Yang D, Ma H and Wang D: The effect of icotinib combined with chemotherapy in untreated non-small-cell lung cancer that harbored EGFR-sensitive mutations in a real-life setting: A retrospective analysis. Onco Targets Ther. 11:2345–2353. 2018. View Article : Google Scholar : PubMed/NCBI

48 

Shinomiya S, Kaira K, Yamaguchi O, Ishikawa K and Kagamu H: Osimertinib induced cardiomyopathy: A case report. Medicine (Baltimore). 99:e223012020. View Article : Google Scholar : PubMed/NCBI

49 

Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, et al: Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 361:947–957. 2009. View Article : Google Scholar : PubMed/NCBI

50 

Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, et al: Osimertinib or Platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 376:629–640. 2017. View Article : Google Scholar : PubMed/NCBI

51 

Montermini L, Meehan B, Garnier D, Lee WJ, Lee TH, Guha A, Al-Nedawi K and Rak J: Inhibition of oncogenic epidermal growth factor receptor kinase triggers release of exosome-like extracellular vesicles and impacts their phosphoprotein and DNA content. J Biol Chem. 290:24534–24546. 2015. View Article : Google Scholar : PubMed/NCBI

52 

Tjin Tham Sjin R, Lee K, Walter AO, Dubrovskiy A, Sheets M, Martin TS, Labenski MT, Zhu Z, Tester R, Karp R, et al: In vitro and in vivo characterization of irreversible mutant-selective EGFR inhibitors that are wild-type sparing. Mol Cancer Ther. 13:1468–1479. 2014. View Article : Google Scholar : PubMed/NCBI

53 

Kobayashi Y and Mitsudomi T: Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy. Cancer Sci. 107:1179–1186. 2016. View Article : Google Scholar : PubMed/NCBI

54 

Hochmair MJ, Morabito A, Hao D, Yang CT, Soo RA, Yang JC, Gucalp R, Halmos B, Märten A and Cufer T: Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: Final analysis of the GioTag study. Future Oncol. 16:2799–2808. 2020. View Article : Google Scholar : PubMed/NCBI

55 

Popat S, Jung HA, Lee SY, Hochmair MJ, Lee SH, Escriu C, Lee MK, Migliorino MR, Lee YC, Girard N, et al: Sequential afatinib and osimertinib in patients with EGFR mutation-positive NSCLC and acquired T790M: A global non-interventional study (UpSwinG). Lung Cancer. 162:9–15. 2021. View Article : Google Scholar : PubMed/NCBI

56 

Miura S, Jung HA, Lee SY, Lee SH, Lee MK, Lee YC, Hochmair MJ, Yang CT, Märten A, Yang JC, et al: Sequential afatinib and osimertinib in asian patients with EGFR Mutation-Positive non-small cell lung cancer and acquired T790M: Combined analysis of two global non-interventional studies. Onco Targets Ther. 15:873–882. 2022. View Article : Google Scholar : PubMed/NCBI

57 

Haratake N, Misumi T, Yamanaka T and Seto T: Optimizing sequential treatment with EGFR tyrosine kinase inhibitor with a simulation of the T790M mutation rate in EGFR-mutated lung cancer. JTO Clin Res Rep. 1:1000852020.PubMed/NCBI

58 

Hsu PC, Chang JW, Chang CF, Huang CY, Yang CT, Kuo CS, Fang YF and Wu CE: Sequential treatment in advanced non-small cell lung cancer harboring EGFR mutations. Ther Adv Respir Dis. 16:175346662211327312022. View Article : Google Scholar : PubMed/NCBI

59 

La Monica S, Madeddu D, Tiseo M, Vivo V, Galetti M, Cretella D, Bonelli M, Fumarola C, Cavazzoni A, Falco A, et al: Combination of gefitinib and pemetrexed prevents the acquisition of TKI resistance in NSCLC cell lines carrying EGFR-activating mutation. J Thorac Oncol. 11:1051–1063. 2016. View Article : Google Scholar : PubMed/NCBI

60 

La Monica S, Minari R, Cretella D, Flammini L, Fumarola C, Bonelli M, Cavazzoni A, Digiacomo G, Galetti M, Madeddu D, et al: Third generation EGFR inhibitor osimertinib combined with pemetrexed or cisplatin exerts long-lasting anti-tumor effect in EGFR-mutated pre-clinical models of NSCLC. J Exp Clin Cancer Res. 38:2222019. View Article : Google Scholar : PubMed/NCBI

61 

Stylianopoulos T, Munn LL and Jain RK: Reengineering the physical microenvironment of tumors to improve drug delivery and efficacy: From mathematical modeling to bench to bedside. Trends Cancer. 4:292–319. 2018. View Article : Google Scholar : PubMed/NCBI

62 

Viloria-Petit A, Crombet T, Jothy S, Hicklin D, Bohlen P, Schlaeppi JM, Rak J and Kerbel RS: Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: A role for altered tumor angiogenesis. Cancer Res. 61:5090–5101. 2001.PubMed/NCBI

63 

Naumov GN, Nilsson MB, Cascone T, Briggs A, Straume O, Akslen LA, Lifshits E, Byers LA, Xu L, Wu HK, et al: Combined vascular endothelial growth factor receptor and epidermal growth factor receptor (EGFR) blockade inhibits tumor growth in xenograft models of EGFR inhibitor resistance. Clin Cancer Res. 15:3484–3494. 2009. View Article : Google Scholar : PubMed/NCBI

64 

Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, Kim JH, Wang X, Enatsu S, Puri T, et al: Randomized Phase II trial of gefitinib with and without pemetrexed as first-line therapy in patients with advanced nonsquamous non-small-cell lung cancer with activating epidermal growth factor receptor mutations. J Clin Oncol. 34:3258–3266. 2016. View Article : Google Scholar : PubMed/NCBI

65 

Han B, Jin B, Chu T, Niu Y, Dong Y, Xu J, Gu A, Zhong H, Wang H, Zhang X, et al: Combination of chemotherapy and gefitinib as first-line treatment for patients with advanced lung adenocarcinoma and sensitive EGFR mutations: A randomized controlled trial. Int J Cancer. 141:1249–1256. 2017. View Article : Google Scholar : PubMed/NCBI

66 

Hosomi Y, Morita S, Sugawara S, Kato T, Fukuhara T, Gemma A, Takahashi K, Fujita Y, Harada T, Minato K, et al: Gefitinib alone versus gefitinib plus chemotherapy for non-small-cell lung cancer with mutated epidermal growth factor receptor: NEJ009 study. J Clin Oncol. 38:115–123. 2020. View Article : Google Scholar : PubMed/NCBI

67 

Miyauchi E, Morita S, Nakamura A, Hosomi Y, Watanabe K, Ikeda S, Seike M, Fujita Y, Minato K, Ko R, et al: Updated analysis of NEJ009: Gefitinib-alone versus gefitinib plus chemotherapy for Non-small-cell lung cancer with mutated EGFR. J Clin Oncol. 40:3587–3592. 2022. View Article : Google Scholar : PubMed/NCBI

68 

Janne P, Planchard D, Cheng Y, Kulkarni D, Huang X and Kobayashi K: Osimertinib with/without platinum-based chemotherapy as first-line treatment in patients with EGFRm advanced NSCLC (FLAURA2). J Thorac Oncol. 18:S36–S37. 2023. View Article : Google Scholar

69 

Yan X, Wang H, Li P, Zhang G, Zhang M, Yang J, Zhang X, Zheng X and Ma Z: Efficacy of first-line treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) alone or in combination with chemotherapy for advanced non-small cell lung cancer (NSCLC) with low-abundance mutation. Lung Cancer. 128:6–12. 2019. View Article : Google Scholar : PubMed/NCBI

70 

Zhou Q, Xu CR, Cheng Y, Liu YP, Chen GY, Cui JW, Yang N, Song Y, Li XL, Lu S, et al: Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study. Cancer Cell. 39:1279–1291.e1273. 2021. View Article : Google Scholar : PubMed/NCBI

71 

Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, et al: Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): Interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 20:625–635. 2019. View Article : Google Scholar : PubMed/NCBI

72 

Nakagawa K, Garon EB, Seto T, Nishio M, Ponce Aix S, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, et al: Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 20:1655–1669. 2019. View Article : Google Scholar : PubMed/NCBI

73 

Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, et al: Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): An open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 15:1236–1244. 2014. View Article : Google Scholar : PubMed/NCBI

74 

Zhao H, Yao W, Min X, Gu K, Yu G, Zhang Z, Cui J, Miao L, Zhang L, Yuan X, et al: Apatinib plus gefitinib as first-line treatment in advanced EGFR-mutant NSCLC: The phase III ACTIVE study (CTONG1706). J Thorac Oncol. 16:1533–1546. 2021. View Article : Google Scholar : PubMed/NCBI

75 

Lee Y, Kim HR, Hong MH, Lee KH, Park KU, Lee GK, Kim HY, Lee SH, Lim KY, Yoon SJ, et al: A randomized Phase 2 study to compare erlotinib with or without bevacizumab in previously untreated patients with advanced non-small cell lung cancer with EGFR mutation. Cancer. 129:405–414. 2023. View Article : Google Scholar : PubMed/NCBI

76 

Nishio K, Seto T, Nishio M, Reck M, Garon EB, Sakai K, Goto K, Kato T, Nakanishi Y, Takahashi T, et al: Ramucirumab plus erlotinib versus placebo plus erlotinib in patients with untreated metastatic EGFR-Mutated NSCLC: RELAY Japanese subset. JTO Clin Res Rep. 2:1001712021.PubMed/NCBI

77 

Qi Y, Xia X, Shao L, Guo L, Dong Y, Tian J, Xu L, Niu R and Wei S: An updated network meta-analysis of EGFR-TKIs and combination therapy in the first-line treatment of advanced EGFR mutation positive non-small cell lung cancer. Front Oncol. 12:6165462022. View Article : Google Scholar : PubMed/NCBI

78 

Zhang G, Yan B, Guo Y, Yang H and Li J: ‘Sandwich’ Strategy to intensify EGFR blockade by concurrent tyrosine kinase inhibitor and monoclonal antibody treatment in highly selected patients. Front Oncol. 12:9529392022. View Article : Google Scholar : PubMed/NCBI

79 

Goldberg SB, Redman MW, Lilenbaum R, Politi K, Stinchcombe TE, Horn L, Chen EH, Mashru SH, Gettinger SN, Melnick MA, et al: Randomized trial of afatinib plus cetuximab versus afatinib alone for First-Line treatment of EGFR-Mutant non-small-cell lung cancer: Final results from SWOG S1403. J Clin Oncol. 38:4076–4085. 2020. View Article : Google Scholar : PubMed/NCBI

80 

Hassanin SO, Hegab AMM, Mekky RH, Said MA, Khalil MG, Hamza AA and Amin A: Combining in vitro, in vivo, and network pharmacology assays to identify targets and molecular mechanisms of spirulina-derived biomolecules against breast cancer. Mar Drugs. 22:3282024. View Article : Google Scholar : PubMed/NCBI

81 

Li WQ and Cui JW: Non-small cell lung cancer patients with ex19del or exon 21 L858R mutation: Distinct mechanisms, different efficacies to treatments. J Cancer Res Clin Oncol. 146:2329–2338. 2020. View Article : Google Scholar : PubMed/NCBI

82 

Ganti AKP, Loo BW, Bassetti M, Blakely C, Chiang A, D'Amico TA, D'Avella C, Dowlati A, Downey RJ, Edelman M, et al: Small cell lung cancer, version 2.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 19:1441–1464. 2021. View Article : Google Scholar : PubMed/NCBI

83 

Morgillo F, Della Corte CM, Fasano M and Ciardiello F: Mechanisms of resistance to EGFR-targeted drugs: Lung cancer. ESMO Open. 1:e0000602016. View Article : Google Scholar : PubMed/NCBI

84 

Haratake N, Hayashi H, Shimokawa M, Nakano Y, Azuma K, Oki M, Ota K, Yoshioka H, Sakamoto T, Yamamoto N, et al: Phase III Clinical trial for the combination of erlotinib plus ramucirumab compared with osimertinib in previously untreated advanced or recurrent non-small cell lung cancer positive for the L858R mutation of EGFR: REVOL858R (WJOG14420L). Clin Lung Cancer. 23:e257–e263. 2022. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu J, Wang S, Yuan H, Li J and Xing P: Patients with non‑small cell lung cancer with the exon 21 L858R mutation: From distinct mechanisms to epidermal growth factor receptor tyrosine kinase inhibitor treatments (Review). Oncol Lett 29: 109, 2025.
APA
Liu, J., Wang, S., Yuan, H., Li, J., & Xing, P. (2025). Patients with non‑small cell lung cancer with the exon 21 L858R mutation: From distinct mechanisms to epidermal growth factor receptor tyrosine kinase inhibitor treatments (Review). Oncology Letters, 29, 109. https://doi.org/10.3892/ol.2024.14855
MLA
Liu, J., Wang, S., Yuan, H., Li, J., Xing, P."Patients with non‑small cell lung cancer with the exon 21 L858R mutation: From distinct mechanisms to epidermal growth factor receptor tyrosine kinase inhibitor treatments (Review)". Oncology Letters 29.3 (2025): 109.
Chicago
Liu, J., Wang, S., Yuan, H., Li, J., Xing, P."Patients with non‑small cell lung cancer with the exon 21 L858R mutation: From distinct mechanisms to epidermal growth factor receptor tyrosine kinase inhibitor treatments (Review)". Oncology Letters 29, no. 3 (2025): 109. https://doi.org/10.3892/ol.2024.14855
Copy and paste a formatted citation
x
Spandidos Publications style
Liu J, Wang S, Yuan H, Li J and Xing P: Patients with non‑small cell lung cancer with the exon 21 L858R mutation: From distinct mechanisms to epidermal growth factor receptor tyrosine kinase inhibitor treatments (Review). Oncol Lett 29: 109, 2025.
APA
Liu, J., Wang, S., Yuan, H., Li, J., & Xing, P. (2025). Patients with non‑small cell lung cancer with the exon 21 L858R mutation: From distinct mechanisms to epidermal growth factor receptor tyrosine kinase inhibitor treatments (Review). Oncology Letters, 29, 109. https://doi.org/10.3892/ol.2024.14855
MLA
Liu, J., Wang, S., Yuan, H., Li, J., Xing, P."Patients with non‑small cell lung cancer with the exon 21 L858R mutation: From distinct mechanisms to epidermal growth factor receptor tyrosine kinase inhibitor treatments (Review)". Oncology Letters 29.3 (2025): 109.
Chicago
Liu, J., Wang, S., Yuan, H., Li, J., Xing, P."Patients with non‑small cell lung cancer with the exon 21 L858R mutation: From distinct mechanisms to epidermal growth factor receptor tyrosine kinase inhibitor treatments (Review)". Oncology Letters 29, no. 3 (2025): 109. https://doi.org/10.3892/ol.2024.14855
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team