Progress in the targeted therapy for advanced non-small cell lung cancer_West China Medical Journal

Authors：

ZENG Lei ,  YANG Kaixuan

Department of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

YANG Kaixuan, Email: scishiwode@sina.com

Keywords：

Advanced non-small cell lung cancer; Gene mutation; Targeted therapy

DOI：

10.7507/1002-0179.201910086

Video：

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Abstract Full text Figures/Tables Video References Cited by

Systemic therapy is the main treatment for advanced non-small cell lung cancer, but the effect of chemotherapy alone is not good. In recent years, with the discovery of the pathogenic targets of non-small cell lung cancer, new treatment methods such as targeted drugs and immune checkpoint inhibitors are available, which greatly improve the survival time and quality of life of patients with advanced non-small cell lung cancer. Genetic testing is recommended for all patients with advanced non-small cells lung cancer to obtain more precise and individualized treatment. This article focuses on different types of gene mutations and the corresponding molecular targeted drugs in advanced non-small cell lung cancer, in order to better guide clinical treatment.

Citation： ZENG Lei, YANG Kaixuan. Progress in the targeted therapy for advanced non-small cell lung cancer. West China Medical Journal, 2021, 36(1): 102-109. doi: 10.7507/1002-0179.201910086 Copy

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3. Kawaguchi T, Koh Y, Ando M, et al. Prospective analysis of oncogenic driver mutations and environmental factors: Japan molecular epidemiology for lung cancer study. J Clin Oncol, 2016, 34(19): 2247-2257.
4. Shi Y, Au JS, 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.
5. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med, 2009, 361(10): 947-957.
6. 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(25): 2380-2388.
7. Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol, 2010, 11(2): 121-128.
8. Inoue A, Kobayashi K, Maemondo M, et al. Updated overall survival results from a randomized phase Ⅲ trial comparing gefitinib with carboplatin-paclitaxel for chemo- naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol, 2013, 24(1): 54-59.
9. Oizumi S, Kobayashi K, Inoue A, et al. Quality of life with gefitinib in patients with EGFR-mutated non-small cell lung cancer: quality of life analysis of North East Japan study group 002 trial. Oncologist, 2012, 17(6): 863-870.
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12. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol, 2012, 13(3): 239-246.
13. Urata Y, Katakami N, Morita S, et al. Randomized phase Ⅲ study comparing gefitinib with erlotinib in patients with previously treated advanced lung adenocarcinoma: WJOG 5108l. J Clin Oncol, 2016, 34(27): 3248-3257.
14. Yang JJ, Zhou Q, Yan HH, et al. A phase Ⅲ randomised controlled trial of erlotinib vs gefitinib in advanced non-small cell lung cancer with EGFR mutations. Br J Cancer, 2017, 116(5): 568-574.
15. Sequist LV, Yang JC, Yamamoto N, et al. Phase Ⅲ study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J clin Oncol, 2013, 31(27): 3327-3334.
16. Yang JC, Hirsh V, Schuler M, et al. Symptom control and quality of life in LUX-lung 3: a phase Ⅲ study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol, 2013, 31(27): 3342-3350.
17. Wu YL, Zhou C, Hu CP, 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, 2014, 15(2): 213-222.
18. Yang JC, Wu YL, Schuler M, 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, 2015, 16(2): 141-151.
19. Park K, Tan EH, O'Byrne K, 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, 2016, 17(5): 577-589.
20. 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.
21. Jänne PA, Yang JC, Kim DW, et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med, 2015, 372(18): 1689-1699.
22. 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.
23. Pao W, Chmielecki J. Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nat Rev Cancer, 2010, 10(11): 760-774.
24. Seto T, Kato T, Nishio M, 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, 2014, 15(11): 1236-1244.
25. Saito H, Fukuhara T, Furuya N, 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, 2019, 20(5): 625-635.
26. Noronha V, Patil VM, Joshi A, et al. Gefitinib versus gefitinib plus pemetrexed and carboplatin chemotherapy in EGFR-mutated lung cancer. J Clin Oncol, 2019: Jco1901154.
27. 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(9): 1883-1889.
28. Lee CK, Brown C, Gralla RJ, et al. Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. J Natl Cancer Inst, 2013, 105(9): 595-605.
29. Wu YL, Cheng Y, 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.
30. Mok TS, Cheng Y, Zhou X, 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, 2018, 36(22): 2244-2250.
31. Pikor LA, Ramnarine VR, Lam S, et al. Genetic alterations defining NSCLC subtypes and their therapeutic implications. Lung cancer, 2013, 82(2): 179-189.
32. Boland JM, Erdogan S, Vasmatzis G, et al. Anaplastic lymphoma kinase immunoreactivity correlates with ALK gene rearrangement and transcriptional up-regulation in non-small cell lung carcinomas. Hum Pathol, 2009, 40(8): 1152-1158.
33. Inamura K, Takeuchi K, Togashi Y, et al. EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers. J Thorac Oncol, 2008, 3(1): 13-17.
34. Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol, 2009, 27(26): 4247-4253.
35. Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med, 2014, 371(23): 2167-2177.
36. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med, 2013, 368(25): 2385-2394.
37. Solomon BJ, Kim DW, Wu YL, et al. Final overall survival analysis from a study comparing first-line crizotinib versus chemotherapy in ALK-mutation-positive non-small-cell lung cancer. J Clin Oncol, 2018, 36(22): 2251-2258.
38. Hida T, Nokihara H, Kondo M, et al. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet, 2017, 390(10089): 29-39.
39. Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med, 2017, 377(9): 829-838.
40. Camidge DR, Dziadziuszko R, Peters S, et al. Updated efficacy and safety data and impact of the EML4-ALK fusion variant on the efficacy of alectinib in untreated ALK-positive advanced non-small cell lung cancer in the global phase Ⅲ alex study. J Thorac Oncol, 2019, 14(7): 1233-1243.
41. Zhou C, Lu Y, Kim S, et al. Primary results of alesia: a randomised, phase Ⅲ, open-label study of alectinib vs crizotinib in Asian patients with treatment-naïve ALK+ advanced NSCLC. Ann Oncol, 2018, 29(Suppl 9): ix173-ix178.
42. Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): A randomised, open-label, phase 3 study. Lancet, 2017, 389(10072): 917-929.
43. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med, 2018, 379(21): 2027-2039.
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