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REVIEW ARTICLE

Targeted therapy resistance in EGFR-mutant non-small cell lung cancer: Roles of MET, Trop-2-directed antibody–drug conjugates, and molecular monitoring

Kai Yan1† ,  Kewei Tian1† ,  Lailing Du1 ,  Xinling Zhang1 ,  Jinghua Yuan1 ,  Xiangquan Song2* ,  Xiaoping Li1*
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1 Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang , China
2 Hangzhou Xihu District Hospital of Traditional Chinese and Western Medicine, Hangzhou, Zhejiang , China
†These authors contributed equally to this work.
EJMO, 026260304 https://doi.org/10.36922/EJMO026260304
Received: 24 June 2026 | Revised: 16 August 2026 | Accepted: 8 September 2026 | Published online: 23 September 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have substantially improved outcomes in patients with EGFR-mutant non-small cell lung cancer (NSCLC), but acquired resistance remains a major barrier to durable disease control.

Objective: This narrative review summarizes the major mechanisms of EGFR-TKI resistance and evaluates the roles of mesenchymal–epithelial transition factor (MET)-targeted therapy, trophoblast cell-surface antigen 2 (Trop-2)-directed antibody–drug conjugates (ADCs), and molecular monitoring in post-resistance management.

Methods: Relevant randomized controlled trials, translational studies, and consensus guidelines on targeted therapy resistance in NSCLC were identified from PubMed and Web of Science, with emphasis on recent high-quality evidence and seminal studies.

Results: EGFR-TKI resistance arises through on-target EGFR alterations, bypass pathway activation, histologic transformation, and non-genetic adaptation. MET amplification is a clinically relevant bypass mechanism, particularly after third-generation EGFR-TKI exposure, and may support combined EGFR/MET inhibition when confirmed using assay-specific criteria. Trop-2-directed ADCs provide a non-genotype-dependent treatment option for patients with heterogeneous or non-actionable resistance, although Trop-2 expression is not yet a validated universal predictive biomarker. Plasma circulating tumor DNA can facilitate rapid detection of emerging resistance, but negative or discordant plasma findings should be interpreted together with tissue biopsy, disease distribution, and the possibility of histologic transformation. Minimal residual disease assessment remains investigational for treatment-guided decision-making.

Conclusion: Post-EGFR-TKI management should follow a mechanism-guided framework integrating progression pattern, tissue and plasma reassessment, biomarker-specific interpretation, matched therapy, and longitudinal molecular monitoring. Prospective studies are needed to standardize testing thresholds and optimize treatment sequencing.

Graphical abstract
Keywords
Non-small cell lung cancer
Targeted therapy
Epidermal growth factor receptor
Mesenchymal–epithelial transition factor
Trophoblast cell-surface antigen 2
Resistance mechanisms
Funding
This study was financially supported by the Zhejiang Health Information Association Research Program (2025XHZN-Z04). The funder did not participate in the design, performance, or reporting of the current study.
Conflict of interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
References
  1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263. doi: 10.3322/caac.21834
  2. Fox AH, Nishino M, Osarogiagbon RU, et al. Acquiring tissue for advanced lung cancer diagnosis and comprehensive biomarker testing: A National Lung Cancer Roundtable best-practice guide. CA Cancer J Clin. 2023;73(4):358-375. doi: 10.3322/caac.21774
  3. Sonkin D, Thomas A, Teicher BA. Cancer treatments: Past, present, and future. Cancer Genet. 2024;286-287:18-24. doi: 10.1016/j.cancergen.2024.06.002
  4. Rolfo C, Mack P, Scagliotti GV, et al. Liquid Biopsy for Advanced NSCLC: A Consensus Statement From the International Association for the Study of Lung Cancer. J Thorac Oncol. 2021;16(10):1647-1662. doi: 10.1016/j.jtho.2021.06.017
  5. Zhou F, Guo H, Xia Y, et al. The changing treatment landscape of EGFR-mutant non-small-cell lung cancer. Nat Rev Clin Oncol. 2025;22(2):95-116. doi: 10.1038/s41571-024-00971-2
  6. Wu YL, Guarneri V, Voon PJ, et al. Tepotinib plus osimertinib in patients with EGFR-mutated non-small-cell lung cancer with MET amplification following progression on first-line osimertinib (INSIGHT 2): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2024;25(8):989-1002. doi: 10.1016/s1470-2045(24)00270-5
  7. Kuo P, Elboudwarej E, Zavodovskaya M, et al. Trop-2 expression in non-small cell lung cancer. PLoS One. 2025;20(4):e0321555. doi: 10.1371/journal.pone.0321555
  8. Planchard D, Jänne PA, Cheng Y, et al. Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948. doi: 10.1056/NEJMoa2306434
  9. Hendriks LE, Kerr KM, Menis J, et al. Non-oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(4):358-376. doi: 10.1016/j.annonc.2022.12.013
  10. Tian Z, Cen L, Wei F, et al. EGFR mutations in non-small cell lung cancer: Classification, characteristics and resistance to third-generation EGFR-tyrosine kinase inhibitors (Review). Oncol Lett. 2025;30(2):375. doi: 10.3892/ol.2025.15121
  11. Tsuboi M, Herbst RS, John T, et al. Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC. N Engl J Med. 2023;389(2):137-147. doi: 10.1056/NEJMoa2304594
  12. Okuma Y, Kubota K, Shimokawa M, et al. First-Line Osimertinib for Previously Untreated Patients With NSCLC and Uncommon EGFR Mutations: The UNICORN Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2024;10(1):43-51. doi: 10.1001/jamaoncol.2023.5013
  13. Sands J, Ahn MJ, Lisberg A, et al. Datopotamab Deruxtecan in Advanced or Metastatic Non-Small Cell Lung Cancer With Actionable Genomic Alterations: Results From the Phase II TROPION-Lung05 Study. J Clin Oncol. 2025;43(10):1254-1265. doi: 10.1200/jco-24-01349
  14. Pellini B, Chaudhuri AA. Circulating Tumor DNA Minimal Residual Disease Detection of Non-Small-Cell Lung Cancer Treated With Curative Intent. J Clin Oncol. 2022;40(6):567-575. doi: 10.1200/jco.21.01929
  15. Tran HT, Heeke S, Sujit S, et al. Circulating tumor DNA and radiological tumor volume identify patients at risk for relapse with resected, early-stage non-small-cell lung cancer. Ann Oncol. 2024;35(2):183-189. doi: 10.1016/j.annonc.2023.11.008
  16. Zalaquett Z, Catherine Rita Hachem M, Kassis Y, et al. Acquired resistance mechanisms to osimertinib: The constant battle. Cancer Treat Rev. 2023;116:102557. doi: 10.1016/j.ctrv.2023.102557
  17. Liu HR. Liquid biopsy – driven cancer genetics in the ultrasensitive and hyper-data-integration eras. Cancer Adv. 2026;9:e26001-e26032. doi: 10.53388/2026926005
  18. Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(2):113-125. doi: 10.1056/NEJMoa1713137
  19. Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007;316(5827):1039-1043. doi: 10.1126/science.1141478
  20. Batra U, Biswas B, Prabhash K, Krishna MV. Differential clinicopathological features, treatments and outcomes in patients with Exon 19 deletion and Exon 21 L858R EGFR mutation-positive adenocarcinoma non-small-cell lung cancer. BMJ Open Respir Res. 2023;10(1):e001492. doi: 10.1136/bmjresp-2022-001492
  21. Ramalingam SS, Vansteenkiste J, Planchard D, et al. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. N Engl J Med. 2020;382(1):41-50. doi: 10.1056/NEJMoa1913662
  22. Robichaux JP, Le X, Vijayan RSK, et al. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature. 2021;597(7878):732-737. doi: 10.1038/s41586-021-03898-1
  23. Zhang L, Zhang X, Wu L, et al. Aumolertinib as adjuvant therapy in resected EGFR-mutated non-small-cell lung cancer (ARTS): a double-blind, multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2026;27(2):159-168. doi: 10.1016/s1470-2045(25)00643-6
  24. Herbst RS, John T, Grohé C, et al. Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer. Nat Med. 2025;31(6):1958-1968. doi: 10.1038/s41591-025-03577-y
  25. Abbosh C, Birkbak NJ, Wilson GA, et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017;545(7655):446-451. doi: 10.1038/nature22364
  26. Cui Q, Zhang JT, Yin H, et al. Comparison of circulating tumor DNA assays for molecular residual disease detection in non-small cell lung cancer. J Thorac Oncol. 2026:104090. doi: 10.1016/j.jtho.2026.104090
  27. Shi C, Zhang C, Fu Z, et al. Antitumor activity of aumolertinib, a third-generation EGFR tyrosine kinase inhibitor, in non-small-cell lung cancer harboring uncommon EGFR mutations. Acta Pharm Sin B. 2023;13(6):2613-2627. doi: 10.1016/j.apsb.2023.03.007
  28. Shi Y, Wu L, Ji Y, et al. Efficacy and safety of limertinib versus gefitinib as first-line treatment for locally advanced or metastatic non-small-cell lung cancer with EGFR-sensitising mutation: a randomised, double-blind, double-dummy, phase 3 trial. Lancet Respir Med. 2025;13(8):677-686. doi: 10.1016/s2213-2600(25)00121-3
  29. Shi Y, Li B, Wu L, et al. Efficacy and Safety of Limertinib (ASK120067) in Patients With Locally Advanced or Metastatic EGFR Thr790Met-Mutated NSCLC: A Multicenter, Single-Arm, Phase 2b Study. J Thorac Oncol. 2022;17(10):1205-1215. doi: 10.1016/j.jtho.2022.05.011
  30. Qin K, Hong L, Zhang J, Le X. MET Amplification as a Resistance Driver to TKI Therapies in Lung Cancer: Clinical Challenges and Opportunities. Cancers (Basel). 2023;15(3):612. doi: 10.3390/cancers15030612
  31. Peng LX, Jie GL, Li AN, et al. MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors. Exp Hematol Oncol. 2021;10(1):52. doi: 10.1186/s40164-021-00245-y
  32. Caparica R, Yen CT, Coudry R, et al. Responses to Crizotinib Can Occur in High-Level MET-Amplified Non-Small Cell Lung Cancer Independent of MET Exon 14 Alterations. J Thorac Oncol. 2017;12(1):141-144. doi: 10.1016/j.jtho.2016.09.116
  33. Wu YL, Yao Y, Yang JJ, et al. Vebreltinib in MET amplification-driven advanced non-small-cell lung cancer (KUNPENG): A single-arm, multi-cohort, multicentre, phase 2 study. Lancet Oncol. 2026;27(1):36-44. doi: 10.1016/s1470-2045(25)00594-7
  34. Rolfo C, O'Brate A, Menzel C, et al. Liquid and Tissue Biopsies for Identifying MET Exon 14 Skipping NSCLC: Analyses from the Phase II VISION Study of Tepotinib. Clin Cancer Res. 2025;31(13):2675-2684. doi: 10.1158/1078-0432.Ccr-24-4097
  35. Hartmaier RJ, Markovets AA, Ahn MJ, et al. Osimertinib + Savolitinib to Overcome Acquired MET-Mediated Resistance in Epidermal Growth Factor Receptor-Mutated, MET-Amplified Non-Small Cell Lung Cancer: TATTON. Cancer Discov. 2023;13(1):98-113. doi: 10.1158/2159-8290.Cd-22-0586
  36. Sun X, Jia L, Wang T, et al. Trop2 binding IGF2R induces gefitinib resistance in NSCLC by remodeling the tumor microenvironment. J Cancer. 2021;12(17):5310-5319. doi: 10.7150/jca.57711
  37. Fang W, Wu L, Meng X, et al. Sacituzumab Tirumotecan in EGFR-TKI-Resistant, EGFR-Mutated Advanced NSCLC. N Engl J Med. 2026;394(1):13-26. doi: 10.1056/NEJMoa2512071
  38. Killock D. Sacituzumab tirumotecan improves OS in EGFR TKI-resistant NSCLC. Nat Rev Clin Oncol. 2025;22(12):899. doi: 10.1038/s41571-025-01090-2
  39. Ahn MJ, Tanaka K, Paz-Ares L, et al. Datopotamab Deruxtecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer: The Randomized, Open-Label Phase III TROPION-Lung01 Study. J Clin Oncol. 2025;43(3):260-272. doi: 10.1200/jco-24-01544
  40. Johnson M, Garassino MC, Mok T, Mitsudomi T. Treatment strategies and outcomes for patients with EGFR-mutant non-small cell lung cancer resistant to EGFR tyrosine kinase inhibitors: Focus on novel therapies. Lung Cancer. 2022;170:41-51. doi: 10.1016/j.lungcan.2022.05.011
  41. Vokes NI, Chambers E, Nguyen T, et al. Concurrent TP53 Mutations Facilitate Resistance Evolution in EGFR-Mutant Lung Adenocarcinoma. J Thorac Oncol. 2022;17(6):779-792. doi: 10.1016/j.jtho.2022.02.011
  42. Coleman N, Hong L, Zhang J, Heymach J, Hong D, Le X. Beyond epidermal growth factor receptor: MET amplification as a general resistance driver to targeted therapy in oncogene-driven non-small-cell lung cancer. ESMO Open. 2021;6(6):100319. doi: 10.1016/j.esmoop.2021.100319
  43. Shiba-Ishii A, Takemura N, Kawai H, Matsubara D. Histologic transformation of non-small-cell lung cancer in response to tyrosine kinase inhibitors: Current knowledge of genetic changes and molecular mechanisms. Cancer Sci. 2024;115(7):2138-2146. doi: 10.1111/cas.16192
  44. Chhouri H, Alexandre D, Grumolato L. Mechanisms of Acquired Resistance and Tolerance to EGFR Targeted Therapy in Non-Small Cell Lung Cancer. Cancers (Basel). 2023;15(2):504. doi: 10.3390/cancers15020504
  45. Chmielecki J, Gray JE, Cheng Y, et al. Candidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer. Nat Commun. 2023;14(1):1070. doi: 10.1038/s41467-023-35961-y
  46. Lu C, Wei XW, Wang Z, et al. Allelic Context of EGFR C797X-Mutant Lung Cancer Defines Four Subtypes With Heterogeneous Genomic Landscape and Distinct Clinical Outcomes. J Thorac Oncol. 2024;19(4):601-612. doi: 10.1016/j.jtho.2023.11.016
  47. Wang R, Chen Y, Li L, Zhang L, Zhang S. Osimertinib acquired resistance among patients with EGFR-mutated NSCLC: from molecular mechanisms to clinical therapeutic strategies. Cancer Drug Resist. 2025;8:61. doi: 10.20517/cdr.2025.140
  48. Tamiya A, Osuga M, Harada D, et al. Mechanisms of resistance and correlation between pre-treatment co-alterations and p-prognosis to osimertinib in chemo-naïve advanced non-small cell lung cancer. Lung Cancer. 2024;195:107917. doi: 10.1016/j.lungcan.2024.107917
  49. Chmielecki J, Mok T, Wu YL, et al. Analysis of acquired resistance mechanisms to osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer from the AURA3 trial. Nat Commun. 2023;14(1):1071. doi: 10.1038/s41467-023-35962-x
  50. Catania C, Liu SV, Garassino M, et al. Correlation between treatments and outcomes of patients with EGFR-mutated non-small-cell lung cancer that transitioned into small-cell lung cancer: an international retrospective study. ESMO Open. 2025;10(7):105326. doi: 10.1016/j.esmoop.2025.105326
  51. Saalfeld FC, Möller J, Christopoulos P, et al. Small cell transformation in EGFR-mutated non-small cell lung cancer: DLL3 expression and efficacy of immune checkpoint inhibitors or tyrosine kinase inhibitors combined with chemotherapy. Eur J Cancer. 2024;213:115065. doi: 10.1016/j.ejca.2024.115065
  52. Chen Y, He M, Dai Z, et al. Clinical and molecular profiling of EGFR-mutant lung adenocarcinomas transformation to small cell lung cancer during TKI treatment. Front Oncol. 2023;13:1308313. doi: 10.3389/fonc.2023.1308313
  53. Dela Cruz MCP, Medina PMB. Epithelial-mesenchymal transition (EMT) and its role in acquired epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) chemoresistance in non-small cell lung cancer (NSCLC). Cancer Pathog Ther. 2025;3(3):215-225. doi: 10.1016/j.cpt.2024.07.001
  54. Lailler C, Didelot A, Garinet S, et al. PrP(C) controls epithelial-to-mesenchymal transition in EGFR-mutated NSCLC: implications for TKI resistance and patient follow-up. Oncogene. 2024;43(37):2781-2794. doi: 10.1038/s41388-024-03130-0
  55. Lim SM, Fujino T, Kim C, et al. BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant EGFR Mutations in Non-Small Cell Lung Cancer. Clin Cancer Res. 2023;29(16):3004-3016. doi: 10.1158/1078-0432.Ccr-22-3901
  56. Su C, Sun SY. Fourth-generation epidermal growth factor receptor-tyrosine kinases inhibitors: hope and challenges. Transl Cancer Res. 2024;13(8):3929-3934. doi: 10.21037/tcr-24-406
  57. Xu J, Zhu A, Xu Y, et al. Real-world analysis of subsequent-line strategies for EGFR C797S mutant non-small cell lung cancer patients acquired resistance to third-generation EGFR tyrosine kinase inhibitors. BMC Cancer. 2025;25(1):1879. doi: 10.1186/s12885-025-15335-x
  58. Hu D, Hu Y, Lei S, Wu D, Wang Y. MET tyrosine kinase inhibitors in combination with EGFR tyrosine kinase inhibitors in NSCLC patients with EGFR mutations and acquired MEt alterations: a systematic review and meta-analysis. BMC Cancer. 2025;25(1):732. doi: 10.1186/s12885-025-14145-5
  59. Zhou X, Zeng L, Huang Z, et al. Strategies Beyond 3rd EGFR-TKI Acquired Resistance: Opportunities and Challenges. Cancer Med. 2025;14(9):e70921. doi: 10.1002/cam4.70921
  60. Ahn MJ, Cho BC, Felip E, et al. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med. 2023;389(22):2063-2075. doi: 10.1056/NEJMoa2307980
  61. Cooper AJ, Herzberg B, Parma M, et al. Multi-Institution Analysis of Tarlatamab for the Treatment of EGFR-Mutant Transformed Small Cell Lung Cancer. JCO Precis Oncol. 2025;9:e2500538. doi: 10.1200/po-25-00538
  62. Papadimitrakopoulou VA, Mok TS, Han JY, et al. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020;31(11):1536-1544. doi: 10.1016/j.annonc.2020.08.2100
  63. Zhang D, Zhao J, Yang Y, et al. Fourth-generation EGFR-TKI to overcome C797S mutation: past, present, and future. J Enzyme Inhib Med Chem. 2025;40(1):2481392. doi: 10.1080/14756366.2025.2481392
  64. Corvaja C, Passaro A, Attili I, et al. Advancements in fourth-generation EGFR TKIs in EGFR-mutant NSCLC: Bridging biological insights and therapeutic development. Cancer Treat Rev. 2024;130:102824. doi: 10.1016/j.ctrv.2024.102824
  65. Yamaoka T, Ohmori T, Ohba M, et al. Acquired Resistance Mechanisms to Combination Met-TKI/EGFR-TKI Exposure in Met-Amplified EGFR-TKI-Resistant Lung Adenocarcinoma Harboring an Activating EGFR Mutation. Mol Cancer Ther. 2016;15(12):3040-3054. doi: 10.1158/1535-7163.Mct-16-0313
  66. Takezawa K, Pirazzoli V, Arcila ME, et al. HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutation. Cancer Discov. 2012;2(10):922-933. doi: 10.1158/2159-8290.Cd-12-0108
  67. Rock A, Mambetsariev I, Pareek S, et al. Small Cell Transformation of EGFR-Mutant NSCLC Treated with Tyrosine Kinase Inhibition. Curr Oncol. 2025;32(10):554. doi: 10.3390/curroncol32100554
  68. Zhu X, Chen L, Liu L, Niu X. EMT-Mediated Acquired EGFR-TKI Resistance in NSCLC: Mechanisms and Strategies. Front Oncol. 2019;9:1044. doi: 10.3389/fonc.2019.01044
  69. Gray JE, Markovets A, Reungwetwattana T, et al. Longitudinal Analyses of Circulating Tumor DNA for the Detection of EGFR Mutation-Positive Advanced NSCLC Progression During Treatment: Data From FLAURA and AURA3. J Thorac Oncol. 2024;19(11):1525-1538. doi: 10.1016/j.jtho.2024.07.008
  70. Leonetti A, Verzè M, Minari R, et al. Resistance to osimertinib in advanced EGFR-mutated NSCLC: a prospective study of molecular genotyping on tissue and liquid biopsies. Br J Cancer. 2024;130(1):135-142. doi: 10.1038/s41416-023-02475-9
  71. Gale D, Heider K, Ruiz-Valdepenas A, et al. Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer. Ann Oncol. 2022;33(5):500-510. doi: 10.1016/j.annonc.2022.02.007
  72. Jeon H, Wang S, Song J, Gill H, Cheng H. Update 2025: Management of Non-Small-Cell Lung Cancer. Lung. 2025;203(1):53. doi: 10.1007/s00408-025-00801-x
  73. Ernst SM, Aldea M, von der Thüsen JH, et al. Utilizing ctDNA to discover mechanisms of resistance to targeted therapies in patients with metastatic NSCLC: towards more informative trials. Nat Rev Clin Oncol. 2025;22(5):371-378. doi: 10.1038/s41571-025-01011-3
  74. Yamaguchi T, Masago K, Sasaki E, Kuroda H, Matsushita H, Horio Y. EML4-ALK Variant 3a/b as a mechanism of osimertinib resistance in a patient with EGFR L858R positive NSCLC. Cancer Genet. 2024;280-281:13-16. doi: 10.1016/j.cancergen.2023.12.001
  75. de Langen AJ, Johnson ML, Mazieres J, et al. Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS(G12C) mutation: a randomised, open-label, phase 3 trial. Lancet. 2023;401(10378):733-746. doi: 10.1016/s0140-6736(23)00221-0
  76. Jänne PA, Riely GJ, Gadgeel SM, et al. Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRAS(G12C) Mutation. N Engl J Med. 2022;387(2):120-131. doi: 10.1056/NEJMoa2204619
  77. de Marinis F, Kim TM, Bonanno L, et al. Savolitinib plus osimertinib in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer with MET overexpression and/or amplification following disease progression on osimertinib: primary results from the phase II SAVANNAH study. Ann Oncol. 2025;36(8):920-933. doi: 10.1016/j.annonc.2025.04.003
  78. Nogami N, Barlesi F, Socinski MA, et al. IMpower150 Final Exploratory Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC Patient Subgroups With EGFR Mutations or Metastases in the Liver or Brain. J Thorac Oncol. 2022;17(2):309-323. doi: 10.1016/j.jtho.2021.09.014
  79. Trontzas IP, He M, Wurtz A, et al. Quantitative Protein Expression of Antibody-Drug Conjugate Targets in EGFR Mutated and Wild-type Non-Small Cell Lung Cancer. Clin Cancer Res. 2025;31(13):2767-2776. doi: 10.1158/1078-0432.Ccr-24-3347
  80. Sakata Y, Saito G, Sakata S, et al. Osimertinib as first-line treatment for elderly patients with advanced EGFR mutation-positive non-small cell lung cancer in a real-world setting (OSI-FACT-EP). Lung Cancer. 2023;186:107426. doi: 10.1016/j.lungcan.2023.107426
  81. Nguyen TNH, Van QL, Thi Bich PN, et al. Therapeutic Outcomes of Osimertinib in EGFR-Mutant Non-Small Cell Lung Cancer With Brain Metastases: Results From a Retrospective Study at Vietnam National Cancer Hospital. Cancer Control. 2025;32:10732748251348429. doi: 10.1177/10732748251348429
  82. Areses Manrique MC, León-Mateos L, Silva-Díaz S, et al. Real-world clinical experience with osimertinib in advanced EGFR-mutated non-small cell lung cancer. Clin Transl Oncol. 2025;28(2):494-503. doi: 10.1007/s12094-025-04015-8
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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