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Systemic treatment of EGFR-mutated non-small cell lung cancer

Rafał Ł. Czyżykowski12, Ewa K. Wrona34, Agata Tałajko3, Aleksandra M. Hasińska3, Piotr J. Potemski14


Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a significant global health challenge, responsible for a substantial portion of cancer-related deaths. This review focuses on the pivotal role of epidermal growth factor receptor gene (EGFR) mutations in NSCLC, exploring their prevalence, diagnostic methods, and implications for targeted therapy. Common mutations in EGFR, constituting approximately 90% of all mutations, are associated with better prognosis and predict favourable response to EGFR tyrosine kinase inhibitors. Meanwhile, the remaining 10–15% comprise atypical mutations, including uncommon exon 18 mutations, exon 20 insertions, de novo T790M mutations, compound mutations, and others. The frequency of uncommon mutations has recently increased, posing challenges due to their largely unknown biological and clinical implications. The review underscores the necessity of summarizing recent scientific discoveries in EGFR mutations to enhance our understanding of their diverse nature and optimize targeted therapeutic approaches in NSCLC patients.

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  1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3): 209–249.
  2. Riely GJ, Kris MG, Rosenbaum D, et al. Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. Clin Cancer Res. 2008; 14(18): 5731–5734.
  3. Friedlaender A, Subbiah V, Russo A, et al. EGFR and HER2 exon 20 insertions in solid tumours: from biology to treatment. Nat Rev Clin Oncol. 2022; 19(1): 51–69.
  4. Wang J, Lam D, Yang J, et al. Discovery of mobocertinib, a new irreversible tyrosine kinase inhibitor indicated for the treatment of non-small-cell lung cancer harboring EGFR exon 20 insertion mutations. Med Chem Res. 2022; 31(10): 1647–1662.
  5. Barlesi F, Mazieres J, Merlio JP, et al. Biomarkers France contributors. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet. 2016; 387(10026): 1415–1426.
  6. Shi Y, Au JSK, Thongprasert S, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol. 2014; 9(2): 154–162.
  7. Mok T, Wu YL, Thongprasert S, et al. Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma. N Engl J Med. 2009; 361(10): 947–957.
  8. Yang JCH, Sequist LV, Geater SL, et al. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015; 16(7): 830–838.
  9. Kitadai R, Okuma Y. Treatment Strategies for Non-Small Cell Lung Cancer Harboring Common and Uncommon EGFR Mutations: Drug Sensitivity Based on Exon Classification, and Structure-Function Analysis. Cancers (Basel). 2022; 14(10).
  10. John T, Taylor A, Wang H, et al. Uncommon EGFR mutations in non-small-cell lung cancer: A systematic literature review of prevalence and clinical outcomes. Cancer Epidemiol. 2022; 76: 102080.
  11. Robichaux JP, Le X, Vijayan RSK, et al. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature. 2021; 597(7878): 732–737.
  12. Zwierenga F, van Veggel BA, van den Berg A, et al. A comprehensive overview of the heterogeneity of EGFR exon 20 variants in NSCLC and (pre)clinical activity to currently available treatments. Cancer Treat Rev. 2023; 120: 102628.
  13. Elamin YY, Robichaux JP, Carter BW, et al. Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity. Cancer Cell. 2022; 40(7): 754–767.e6.
  14. Kohsaka S, Petronczki M, Solca F, et al. Tumor clonality and resistance mechanisms in EGFR mutation-positive non-small-cell lung cancer: implications for therapeutic sequencing. Future Oncol. 2019; 15(6): 637–652.
  15. Attili I, Passaro A, Pisapia P, et al. Uncommon Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence. Curr Oncol. 2022; 29(1): 255–266.
  16. Yang JCH, Schuler M, Popat S, et al. Afatinib for the Treatment of Non-Small Cell Lung Cancer Harboring Uncommon Mutations: An Updated Database of 1023 Cases Brief Report. Front Oncol. 2022; 12: 834704.
  17. Janning M, Süptitz J, Albers-Leischner C, et al. National Network Genomic Medicine Lung Cancer (nNGM). Treatment outcome of atypical EGFR mutations in the German National Network Genomic Medicine Lung Cancer (nNGM). Ann Oncol. 2022; 33(6): 602–615.
  18. Bar J, Peled N, Schokrpur S, et al. UNcommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-Life Practice in First-LiNe Setting (UNICORN). J Thorac Oncol. 2023; 18(2): 169–180.
  19. Skoulidis F, Heymach JV. Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy. Nat Rev Cancer. 2019; 19(9): 495–509.
  20. Ji J, Aredo JV, Piper-Vallillo A, et al. Osimertinib in NSCLC With Atypical -Activating Mutations: A Retrospective Multicenter Study. JTO Clin Res Rep. 2023; 4(3): 100459.
  21. Kim Y, Lee B, Shim JHo, et al. Concurrent Genetic Alterations Predict the Progression to Target Therapy in EGFR-Mutated Advanced NSCLC. J Thorac Oncol. 2019; 14(2): 193–202.
  22. Yue D, Xu S, Wang Q, et al. Erlotinib versus vinorelbine plus cisplatin as adjuvant therapy in Chinese patients with stage IIIA EGFR mutation-positive non-small-cell lung cancer (EVAN): a randomised, open-label, phase 2 trial. Lancet Respir Med. 2018; 6(11): 863–873.
  23. Yue D, Xu S, Wang Q, et al. Updated Overall Survival and Exploratory Analysis From Randomized, Phase II EVAN Study of Erlotinib Versus Vinorelbine Plus Cisplatin Adjuvant Therapy in Stage IIIA Epidermal Growth Factor Receptor+ Non-Small-Cell Lung Cancer. J Clin Oncol. 2022; 40(34): 3912–3917.
  24. Li N, Ou W, Ye X, et al. Pemetrexed-carboplatin adjuvant chemotherapy with or without gefitinib in resected stage IIIA-N2 non-small cell lung cancer harbouring EGFR mutations: a randomized, phase II study. Ann Surg Oncol. 2014; 21(6): 2091–2096.
  25. Zhong WZ, Wang Q, Mao WM, et al. ADJUVANT investigators. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study. Lancet Oncol. 2018; 19(1): 139–148.
  26. Zhong WZ, Wang Q, Mao WM, et al. Gefitinib Versus Vinorelbine Plus Cisplatin as Adjuvant Treatment for Stage II-IIIA (N1-N2) EGFR-Mutant NSCLC: Final Overall Survival Analysis of CTONG1104 Phase III Trial. J Clin Oncol. 2021; 39(7): 713–722.
  27. Tada H, Mitsudomi T, Misumi T, et al. West Japan Oncology Group. Randomized Phase III Study of Gefitinib Versus Cisplatin Plus Vinorelbine for Patients With Resected Stage II-IIIA Non-Small-Cell Lung Cancer With Mutation (IMPACT). J Clin Oncol. 2022; 40(3): 231–241.
  28. Wu YL, Tsuboi M, John T, et al. ADAURA Investigators. Osimertinib in Resected -Mutated Non-Small-Cell Lung Cancer. N Engl J Med. 2020; 383(18): 1711–1723.
  29. Herbst RS, Wu YL, John T, et al. Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non-Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial. J Clin Oncol. 2023; 41(10): 1830–1840.
  30. Tsuboi M, Herbst R, John T, et al. Overall Survival with Osimertinib in Resected EGFR -Mutated NSCLC. N Engl J Med. 2023; 389(2): 137–147.
  31. 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(9): 1877–1883.
  32. Yoshioka H, Shimokawa M, Seto T, et al. Final overall survival results of WJTOG3405, a randomized phase III trial comparing gefitinib versus cisplatin with docetaxel as the first-line treatment for patients with stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. Ann Oncol. 2019; 30(12): 1978–1984.
  33. Paz-Ares L, Tan EH, O'Byrne K, 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. 2017; 28(2): 270–277.
  34. Mok TSK, Kim SW, Wu YL, et al. Gefitinib Plus Chemotherapy Versus Chemotherapy in Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer Resistant to First-Line Gefitinib (IMPRESS): Overall Survival and Biomarker Analyses. J Clin Oncol. 2017; 35(36): 4027–4034.
  35. Cheng Y, Mok TS, Zhou X, 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. 2017; 18(11): 1454–1466.
  36. Soria JC, Ohe Y, Vansteenkiste J, et al. FLAURA Investigators. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018; 378(2): 113–125.
  37. Ramalingam SS, Vansteenkiste J, Planchard D, et al. FLAURA Investigators. Programmed Cell Death Ligand 1 Expression in Untreated EGFR Mutated Advanced NSCLC and Response to Osimertinib Versus Comparator in FLAURA. J Thorac Oncol. 2020; 15(1): 138–143.
  38. Ito K, Morise M, Wakuda K, 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. 2021; 6(3): 100115.
  39. Park K, Bennouna J, Boyer M, et al. Sequencing of therapy following first-line afatinib in patients with EGFR mutation-positive non-small cell lung cancer. Lung Cancer. 2019; 132: 126–131.
  40. Hochmair MJ, Morabito A, Hao D, et al. Sequential afatinib and osimertinib in patients with mutation-positive non-small-cell lung cancer: updated analysis of the observational GioTag study. Future Oncol. 2019; 15(25): 2905–2914.
  41. Lee KiH, Cho BC, Ahn MJ, et al. Lazertinib Versus Gefitinib as First-Line Treatment in Patients With -Mutated Advanced Non-Small-Cell Lung Cancer: Results From LASER301. J Clin Oncol. 2023; 41(26): 4208–4217.
  42. Cho BC, Felip E, Spira AI, et al. LBA14 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. 2023; 34: S1306.
  43. Lu S, Dong X, Jian H, 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 Exon 19 Deletion or L858R Mutations. J Clin Oncol. 2022; 40(27): 3162–3171.
  44. Shi Y, Chen G, Wang X, et al. FURLONG investigators. Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study. Lancet Respir Med. 2022; 10(11): 1019–1028.
  45. Rocco D, Della Gravara L, Palazzolo G, et al. The role of antiangiogenic monoclonal antibodies combined to EGFR-TKIs in the treatment of advanced non-small cell lung cancer with activating EGFR mutations: acquired resistance mechanisms and strategies to overcome them. Cancer Drug Resist. 2022; 5(4): 1016–1024.
  46. Qi Y, Xia X, Shao L, et al. 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. 2022; 12: 616546.
  47. Kenmotsu H, Wakuda K, Mori K, et al. Randomized Phase 2 Study of Osimertinib Plus Bevacizumab Versus Osimertinib for Untreated Patients With Nonsquamous NSCLC Harboring EGFR Mutations: WJOG9717L Study. J Thorac Oncol. 2022; 17(9): 1098–1108.
  48. Soo RA, Han JY, Dafni U, et al. ETOP 10-16 BOOSTER Collaborators. A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial. Ann Oncol. 2022; 33(2): 181–192.
  49. Ishikawa N, Ninomiya T, Kozuki T, et al. Afatinib (Afa) + bevacizumab (Bev) versus afatinib alone as first-line treatment of patients with EGFR-mutated advanced non-squamous NSCLC: Primary analysis of the multicenter, randomized, phase II study—AfaBev-CS study. J Clin Oncol. 2022; 40(16_suppl): 9112–9112.
  50. Akamatsu H, Toi Y, Hayashi H, et al. Efficacy of Osimertinib Plus Bevacizumab vs Osimertinib in Patients With EGFR T790M-Mutated Non-Small Cell Lung Cancer Previously Treated With Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor: West Japan Oncology Group 8715L Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021; 7(3): 386–394.
  51. Mosca M, Conci N, Di Federico A, et al. First-Generation Epidermal Growth Factor Receptor Inhibitors Plus Antiangiogenic Drugs Versus Third-Generation Epidermal Growth Factor Receptor Inhibitors in Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis. JCO Precis Oncol. 2023; 7: e2300073.
  52. Wu YL, Lee JS, Thongprasert S, et al. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol. 2013; 14(8): 777–786.
  53. Noronha V, Patil VM, Joshi A, et al. Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in -Mutated Lung Cancer. J Clin Oncol. 2020; 38(2): 124–136.
  54. Hosomi Y, Morita S, Sugawara S, et al. North-East Japan Study Group. Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study. J Clin Oncol. 2020; 38(2): 115–123.
  55. Wang BC, Zhang WX, Kuang BH, et al. The efficacy and tolerability of combining pemetrexed-based chemotherapy with gefitinib in the first-line treatment of non-small cell lung cancer with mutated EGFR: A pooled analysis of randomized clinical trials. PLoS One. 2022; 17(10): e0275919.
  56. Planchard D, Jänne P, Cheng Y, et al. Osimertinib with or without Chemotherapy in EGFR -Mutated Advanced NSCLC. N Engl J Med. 2023; 389(21): 1935–1948.
  57. Creelan BC, Yeh TC, Kim SW, et al. A Phase 1 study of gefitinib combined with durvalumab in EGFR TKI-naive patients with EGFR mutation-positive locally advanced/metastatic non-small-cell lung cancer. Br J Cancer. 2021; 124(2): 383–390.
  58. Gettinger S, Hellmann MD, Chow LQM, et al. Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC. J Thorac Oncol. 2018; 13(9): 1363–1372.
  59. Yang JCH, Gadgeel SM, Sequist LV, et al. Pembrolizumab in Combination With Erlotinib or Gefitinib as First-Line Therapy for Advanced NSCLC With Sensitizing EGFR Mutation. J Thorac Oncol. 2019; 14(3): 553–559.
  60. Ahn MJ, Cho BC, Ou X, et al. Osimertinib Plus Durvalumab in Patients With EGFR-Mutated, Advanced NSCLC: A Phase 1b, Open-Label, Multicenter Trial. J Thorac Oncol. 2022; 17(5): 718–723.
  61. Rudin CM, Cervantes A, Dowlati A, et al. Safety and clinical activity of atezolizumab plus erlotinib in patients with non-small-cell lung cancer. ESMO Open. 2023; 8(2): 101160.
  62. Johnson M, Garassino MC, Mok T, et al. 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.
  63. Girard N. Optimizing outcomes in EGFR mutation-positive NSCLC: which tyrosine kinase inhibitor and when? Future Oncol. 2018; 14(11): 1117–1132.
  64. Lu C, Wei XW, Wang Z, et al. AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017; 376(7): 629–640.
  65. Eide IJ, Helland Å, Ekman S, et al. Osimertinib in T790M-positive and -negative patients with EGFR-mutated advanced non-small cell lung cancer (the TREM-study). Lung Cancer. 2020; 143: 27–35.
  66. Ahn MJ, Yang J, Yu H, et al. 136O: Osimertinib combined with durvalumab in EGFR-mutant non-small cell lung cancer: Results from the TATTON phase Ib trial. J Thorac Oncol. 2016; 11(4): S115.
  67. Cho BC, Kim DW, Spira AI, et al. Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial. Nat Med. 2023; 29(10): 2577–2585.
  68. Shu C, Goto K, Ohe Y, et al. Amivantamab and lazertinib in patients with EGFR-mutant non–small cell lung (NSCLC) after progression on osimertinib and platinum-based chemotherapy: Updated results from CHRYSALIS-2. J Clin Oncol. 2022; 40(16_suppl): 9006–9006.
  69. Passaro A, Wang J, Wang Y, et al. MARIPOSA-2 Investigators. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann Oncol. 2024; 35(1): 77–90.
  70. Lee CK, Man J, Lord S, et al. Clinical and Molecular Characteristics Associated With Survival Among Patients Treated With Checkpoint Inhibitors for Advanced Non-Small Cell Lung Carcinoma: A Systematic Review and Meta-analysis. JAMA Oncol. 2018; 4(2): 210–216.
  71. Yang JH, Lee D, Lee JS, et al. Pemetrexed and platinum with or without pembrolizumab for tyrosine kinase inhibitor (TKI)-resistant, EGFR-mutant, metastatic nonsquamous NSCLC: Phase 3 KEYNOTE-789 study. J Clin Oncol. 2023; 41(17_suppl): LBA9000–LBA9000.
  72. Mok TSK. Individualising treatments for oncogene addicted lung cancer. ESMO Asia Congress 2022.
  73. Jiang T, Wang P, Zhang J, et al. Toripalimab plus chemotherapy as second-line treatment in previously EGFR-TKI treated patients with EGFR-mutant-advanced NSCLC: a multicenter phase-II trial. Signal Transduct Target Ther. 2021; 6(1): 355.
  74. Nogami N, Barlesi F, Socinski M, 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.
  75. Lu S, Wu L, Jian H, et al. Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2022; 23(9): 1167–1179.
  76. Lu S, Wu L, Jian H, et al. Sintilimab plus chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer with disease progression after EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): second interim analysis from a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Respir Med. 2023; 11(7): 624–636.
  77. 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(2): 189–194.
  78. 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(5): 793–799.
  79. Kobayashi Y, Mitsudomi T. Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy. Cancer Sci. 2016; 107(9): 1179–1186.
  80. Cho JHo, Lim SH, An HoJ, et al. Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09). J Clin Oncol. 2020; 38(5): 488–495.
  81. Villaruz LC, Wang X, Bertino EM, et al. A single-arm, multicenter, phase II trial of osimertinib in patients with epidermal growth factor receptor exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations. ESMO Open. 2023; 8(2): 101183.
  82. Yasuda H, Ichihara E, Sakakibara-Konishi J, et al. A phase I/II study of osimertinib in EGFR exon 20 insertion mutation-positive non-small cell lung cancer. Lung Cancer. 2021; 162: 140–146.
  83. Piotrowska Z, Wang Y, Sequist L, et al. ECOG-ACRIN 5162: A phase II study of osimertinib 160 mg in NSCLC with EGFR exon 20 insertions. J Clin Oncol. 2020; 38(15_suppl): 9513–9513.
  84. Zwierenga F, van Veggel B, Hendriks LEL, et al. High dose osimertinib in patients with advanced stage EGFR exon 20 mutation-positive NSCLC: Results from the phase 2 multicenter POSITION20 trial. Lung Cancer. 2022; 170: 133–140.
  85. Cardona AF, Rojas L, Zatarain-Barrón ZL, et al. CLICaP. EGFR exon 20 insertion in lung adenocarcinomas among Hispanics (geno1.2-CLICaP). Lung Cancer. 2018; 125: 265–272.
  86. Shah MP, Aredo JV, Padda SK, et al. EGFR exon 20 Insertion NSCLC and Response to Platinum-Based Chemotherapy. Clin Lung Cancer. 2022; 23(2): e148–e153.
  87. Yang G, Li J, Xu H, et al. EGFR exon 20 insertion mutations in Chinese advanced non-small cell lung cancer patients: Molecular heterogeneity and treatment outcome from nationwide real-world study. Lung Cancer. 2020; 145: 186–194.
  88. Negrao M, Reuben A, Robichaux J, et al. Association of EGFR and HER-2 exon 20 mutations with distinct patterns of response to immune checkpoint blockade in non-small cell lung cancer. J Clin Oncol. 2018; 36(15_suppl): 9052–9052.
  89. Park K, Haura EB, Leighl NB, et al. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study. J Clin Oncol. 2021; 39(30): 3391–3402.
  90. Girard N, Park K, Tang K, et al. LBA5 Amivantamab plus chemotherapy vs chemotherapy as first-line treatment in EGFR Exon 20 insertion-mutated advanced non-small cell lung cancer (NSCLC): Primary results from PAPILLON, a randomized phase III global study. Ann Oncol. 2023; 34: S1304.
  91. Ramalingam SS, Zhou C, Kim TM, et al. Mobocertinib (TAK-788) in EGFR exon 20 insertion (ex20ins)+ metastatic NSCLC (mNSCLC): Additional results from platinum-pretreated patients (pts) and EXCLAIM cohort of phase 1/2 study. J Clin Oncol. 2021; 39(15_suppl): 9014–9014.
  92. Elamin YY, Robichaux JP, Carter BW, et al. Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity. Cancer Cell. 2022; 40(7): 754–767.e6.
  93. Janne P, Wang M, Camidge D, et al. Antitumor activity of sunvozertinib in NSCLC patients with EGFR Exon20 insertion mutations after platinum and anti-PD(L)1 treatment failures. J Clin Oncol. 2022; 40(16_suppl): 9015–9015.
  94. Yu HA, Tan DSW, Smit EF, et al. Phase (Ph) 1/2a study of CLN-081 in patients (pts) with NSCLC with EGFR exon 20 insertion mutations (Ins20). J Clin Oncol. 2022; 40(16_suppl): 9007–9007.
  95. Wu SG, Yu CJ, Yang JCH, et al. The effectiveness of afatinib in patients with lung adenocarcinoma harboring complex epidermal growth factor receptor mutation. Ther Adv Med Oncol. 2020; 12: 1758835920946156.
  96. Ji J, Aredo JV, Piper-Vallillo A, et al. Osimertinib in non-small cell lung cancer (NSCLC) with atypical EGFR activating mutations: A retrospective multicenter study. J Clin Oncol. 2020; 38(15_suppl).