Tuberculosis and Respiratory Diseases

  • 제85권2호
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  • Pages.155-164
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  • 2022
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  • 1738-3536(pISSN)
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  • 2005-6184(eISSN)
대한결핵및호흡기학회 (The Korean Academy of Tuberculosis and Respiratory Diseases)
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Pretreatment Neutrophil-to-Lymphocyte Ratio and Smoking History as Prognostic Factors in Advanced Non-Small Cell Lung Cancer Patients Treated with Osimertinib

  • Park, Ji Young (Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital) ;
  • Jang, Seung Hun (Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital) ;
  • Lee, Chang Youl (Lung Research Institute of Hallym University College of Medicine) ;
  • Kim, Taehee (Lung Research Institute of Hallym University College of Medicine) ;
  • Chung, Soo Jie (Lung Research Institute of Hallym University College of Medicine) ;
  • Lee, Ye Jin (Lung Research Institute of Hallym University College of Medicine) ;
  • Kim, Hwan Il (Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital) ;
  • Kim, Joo-Hee (Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital) ;
  • Park, Sunghoon (Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital) ;
  • Hwang, Yong Il (Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital) ;
  • Jung, Ki-Suck (Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital)
  • 투고 : 2021.09.10
  • 심사 : 2022.01.16
  • 발행 : 2022.04.30
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Background: The remarkable efficacy of osimertinib in non-small cell lung cancer (NSCLC) with acquired T790M mutation has been widely documented in clinical trials and real-world practice. However, some patients show primary resistance to this drug. Even patients who initially show a favorable response have inconsistent clinical outcomes later. Therefore, the aim of this study was to identify additional clinical predictive factors for osimertinib efficacy. Methods: A prospective cohort of patients with acquired T790M positive stage IV lung adenocarcinoma treated with osimertinib salvage therapy in Hallym University Medical Center were analyzed. Results: Sixty-one eligible patients were analyzed, including 38 (62%) women and 39 (64%) who never smoked. Their mean age was 63.3 years. The median follow-up after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) was 36.0 months (interquartile range, 24.7-50.2 months). The majority (n=45, 74%) of patients were deceased. Based on univariate analysis, low baseline neutrophil-to-lymphocyte ratios (NLR), age ≥50 years, never-smoking history, stage IVA at osimertinib initiation, and prolonged response to previous TKIs (≥10 months) were associated with a significantly longer progression-free survival (PFS). Multivariate analysis showed that never-smoking status (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.30-0.98; p=0.041) and a baseline NLR less than or equal to 3.5 (HR, 0.23; 95% CI, 0.12-0.45; p<0.001) were independently associated with a prolonged PFS with osimertinib. Conclusion: Smoking history and high NLR were independent negative predictors of osimertinib PFS in patients with advanced NSCLC developing EGFR T790M resistance after the initial EGFR-TKI treatment.

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참고문헌

  1. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361:947-57. https://doi.org/10.1056/NEJMoa0810699
  2. Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013;31:3327-34. https://doi.org/10.1200/JCO.2012.44.2806
  3. Chang YS, Choi CM, Lee JC. Mechanisms of epidermal growth factor receptor tyrosine kinase inhibitor resistance and strategies to overcome resistance in lung adenocarcinoma. Tuberc Respir Dis 2016;79:248-56. https://doi.org/10.4046/trd.2016.79.4.248
  4. Huang YH, Hsu KH, Tseng JS, Chen KC, Hsu CH, Su KY, et al. The association of acquired T790M mutation with clinical characteristics after resistance to first-line epidermal growth factor receptor tyrosine kinase inhibitor in lung adenocarcinoma. Cancer Res Treat 2018;50:1294-303. https://doi.org/10.4143/crt.2017.512
  5. Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med 2017;376:629-40. https://doi.org/10.1056/NEJMoa1612674
  6. Kato Y, Hosomi Y, Watanabe K, Yomota M, Kawai S, Okuma Y, et al. Impact of clinical features on the efficacy of osimertinib therapy in patients with T790M-positive non-small cell lung cancer and acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors. J Thorac Dis 2019;11:2350-60. https://doi.org/10.21037/jtd.2019.06.03
  7. Yoshimura A, Yamada T, Okura N, Takeda T, Hirose K, Kubota Y, et al. Clinical characteristics of osimertinib responder in non-small cell lung cancer patients with EGFR-T790M mutation. Cancers (Basel) 2019;11:365. https://doi.org/10.3390/cancers11030365
  8. Suidan AM, Roisman L, Belilovski Rozenblum A, Ilouze M, Dudnik E, Zer A, et al. Lung cancer in young patients: higher rate of driver mutations and brain involvement, but better survival. J Glob Oncol 2019;5:1-8. https://doi.org/10.1200/JGO.19.11000
  9. Lara MS, Brunson A, Wun T, Tomlinson B, Qi L, Cress R, et al. Predictors of survival for younger patients less than 50 years of age with non-small cell lung cancer (NSCLC): a California Cancer Registry analysis. Lung Cancer 2014;85:264-9. https://doi.org/10.1016/j.lungcan.2014.04.007
  10. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362:2380-8. https://doi.org/10.1056/NEJMoa0909530
  11. Yu Y, Qian L, Cui J. Value of neutrophil-to-lymphocyte ratio for predicting lung cancer prognosis: a meta-analysis of 7,219 patients. Mol Clin Oncol 2017;7:498-506. https://doi.org/10.3892/mco.2017.1342
  12. Ono T, Igawa S, Kurahayashi S, Okuma Y, Sugimoto A, Kusuhara S, et al. Impact of neutrophil-to-lymphocyte ratio in patients with EGFR-mutant NSCLC treated with tyrosine kinase inhibitors. Invest New Drugs 2020;38:885-93. https://doi.org/10.1007/s10637-020-00919-0
  13. Park JY, Jang SH, Kim HI, Kim JH, Park S, Hwang YI, et al. Thyroid transcription factor-1 as a prognostic indicator for stage IV lung adenocarcinoma with and without EGFR-sensitizing mutations. BMC Cancer 2019;19:574. https://doi.org/10.1186/s12885-019-5792-0
  14. Guo Y, Song J, Wang Y, Huang L, Sun L, Zhao J, et al. Concurrent genetic alterations and other biomarkers predict treatment efficacy of EGFR-TKIs in EGFR-mutant non-small cell lung cancer: a review. Front Oncol 2020;10:610923. https://doi.org/10.3389/fonc.2020.610923
  15. Kim Y, Lee B, Shim JH, Lee SH, Park WY, Choi YL, et al. Concurrent genetic alterations predict the progression to target therapy in EGFR-mutated advanced NSCLC. J Thorac Oncol 2019;14:193-202. https://doi.org/10.1016/j.jtho.2018.10.150
  16. Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, 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;16:141-51. https://doi.org/10.1016/S1470-2045(14)71173-8
  17. Hasegawa Y, Ando M, Maemondo M, Yamamoto S, Isa S, Saka H, et al. The role of smoking status on the progression-free survival of non-small cell lung cancer patients harboring activating epidermal growth factor receptor (EGFR) mutations receiving first-line EGFR tyrosine kinase inhibitor versus platinum doublet chemotherapy: a meta-analysis of prospective randomized trials. Oncologist 2015;20:307-15. https://doi.org/10.1634/theoncologist.2014-0285
  18. Lin JH, Lin D, Xu L, Wang Q, Hu HH, Xu HP, et al. The association between clinical prognostic factors and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) efficacy in advanced non-small-cell lung cancer patients: a retrospective assessment of 94 cases with EGFR mutations. Oncotarget 2017;8:3412-21. https://doi.org/10.18632/oncotarget.13787
  19. Zhao D, Chen X, Qin N, Su D, Zhou L, Zhang Q, et al. The prognostic role of EGFR-TKIs for patients with advanced non-small cell lung cancer. Sci Rep 2017;7:40374. https://doi.org/10.1038/srep40374
  20. Kim IA, Lee JS, Kim HJ, Kim WS, Lee KY. Cumulative smoking dose affects the clinical outcomes of EGFR-mutated lung adenocarcinoma patients treated with EGFR-TKIs: a retrospective study. BMC Cancer 2018;18:768. https://doi.org/10.1186/s12885-018-4691-0
  21. Cha YK, Lee HY, Ahn MJ, Park K, Ahn JS, Sun JM, et al. The impact of smoking status on radiologic tumor progression patterns and response to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in lung adenocarcinoma with activating EGFR mutations. J Thorac Dis 2016;8:3175-86. https://doi.org/10.21037/jtd.2016.11.25
  22. Kim MH, Kim HR, Cho BC, Bae MK, Kim EY, Lee CY, et al. Impact of cigarette smoking on response to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in lung adenocarcinoma with activating EGFR mutations. Lung Cancer 2014;84:196-202. https://doi.org/10.1016/j.lungcan.2014.01.022
  23. Chang N, Duan J, Wang L, Dong Z, Liu Z. Patients with advanced non-small cell lung cancer with EGFR mutations in addition to complex mutations treated with osimertinib have a poor clinical outcome: A real-world data analysis. Oncol Lett 2020;20:2266-72. https://doi.org/10.3892/ol.2020.11801
  24. Qin K, Hou H, Liang Y, Zhang X. Prognostic value of TP53 concurrent mutations for EGFR-TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis. BMC Cancer 2020;20:328. https://doi.org/10.1186/s12885-020-06805-5
  25. Tu CY, Cheng FJ, Chen CM, Wang SL, Hsiao YC, Chen CH, et al. Cigarette smoke enhances oncogene addiction to c-MET and desensitizes EGFR-expressing non-small cell lung cancer to EGFR TKIs. Mol Oncol 2018;12:705-23. https://doi.org/10.1002/1878-0261.12193
  26. Ahn BC, Lee JH, Kim MH, Pyo KH, Lee CK, Lim SM, et al. Distinct characteristics and clinical outcomes to predict the emergence of MET amplification in patients with non-small cell lung cancer who developed resistance after treatment with epidermal growth factor receptor tyrosine kinase inhibitors. Cancers (Basel) 2021;13:3096. https://doi.org/10.3390/cancers13123096
  27. Li D, Zhang L, Zhou J, Chen H. Cigarette smoke extract exposure induces EGFR-TKI resistance in EGFR-mutated NSCLC via mediating Src activation and EMT. Lung Cancer 2016;93:35-42. https://doi.org/10.1016/j.lungcan.2015.12.007
  28. Offin M, Rizvi H, Tenet M, Ni A, Sanchez-Vega F, Li BT, et al. Tumor mutation burden and efficacy of EGFR-tyrosine kinase inhibitors in patients with EGFR-mutant lung cancers. Clin Cancer Res 2019;25:1063-9. https://doi.org/10.1158/1078-0432.ccr-18-1102
  29. Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer 2013;13:759-71. https://doi.org/10.1038/nrc3611
  30. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860-7. https://doi.org/10.1038/nature01322
  31. Proctor MJ, Morrison DS, Talwar D, Balmer SM, Fletcher CD, O'Reilly DS, et al. A comparison of inflammation-based prognostic scores in patients with cancer: a Glasgow inflammation outcome study. Eur J Cancer 2011;47:2633-41. https://doi.org/10.1016/j.ejca.2011.03.028
  32. Mizuno R, Kawada K, Itatani Y, Ogawa R, Kiyasu Y, Sakai Y. The role of tumor-associated neutrophils in colorectal cancer. Int J Mol Sci 2019;20:529. https://doi.org/10.3390/ijms20030529
  33. Pinato DJ, Shiner RJ, Seckl MJ, Stebbing J, Sharma R, Mauri FA. Prognostic performance of inflammation-based prognostic indices in primary operable non-small cell lung cancer. Br J Cancer 2014;110:1930-5. https://doi.org/10.1038/bjc.2014.145
  34. Scilla KA, Bentzen SM, Lam VK, Mohindra P, Nichols EM, Vyfhuis MA, et al. Neutrophil-lymphocyte ratio is a prognostic marker in patients with locally advanced (stage IIIA and IIIB) non-small cell lung cancer treated with combined modality therapy. Oncologist 2017;22:737-42. https://doi.org/10.1634/theoncologist.2016-0443
  35. Cedres S, Torrejon D, Martinez A, Martinez P, Navarro A, Zamora E, et al. Neutrophil to lymphocyte ratio (NLR) as an indicator of poor prognosis in stage IV non-small cell lung cancer. Clin Transl Oncol 2012;14:864-9. https://doi.org/10.1007/s12094-012-0872-5
  36. Li Y, Zhang Z, Hu Y, Yan X, Song Q, Wang G, et al. Pretreatment neutrophil-to-lymphocyte ratio (NLR) may predict the outcomes of advanced non-small-cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). Front Oncol 2020;10:654. https://doi.org/10.3389/fonc.2020.00654
  37. Sebastian N, Wu T, Bazan J, Driscoll E, Willers H, Yegya-Raman N, et al. Pre-treatment neutrophil-lymphocyte ratio is associated with overall mortality in localized non-small cell lung cancer treated with stereotactic body radiotherapy. Radiother Oncol 2019;134:151-7. https://doi.org/10.1016/j.radonc.2019.01.032
  38. Xu C, Yao X, Li T, Wang J, An B, Wang J, et al. Pretreatment neutrophil-to-lymphocyte ratio is a predictive biomarker for EGFR TKI-treated patients with advanced EGFR-mutant Non-small cell lung cancer. Transl Cancer Res 2020;9:2875-83. https://doi.org/10.21037/tcr.2020.02.28
  39. Oxnard GR, Thress KS, Alden RS, Lawrance R, Paweletz CP, Cantarini M, et al. Association between plasma genotyping and outcomes of treatment with osimertinib (AZD9291) in advanced non-small-cell lung cancer. J Clin Oncol 2016;34:3375-82. https://doi.org/10.1200/JCO.2016.66.7162
  40. Hong MH, Kim HR, Ahn BC, Heo SJ, Kim JH, Cho BC. Real-world analysis of the efficacy of rebiopsy and EGFR mutation test of tissue and plasma samples in drug-resistant non-small cell lung cancer. Yonsei Med J 2019;60:525-34. https://doi.org/10.3349/ymj.2019.60.6.525
  41. Thress KS, Brant R, Carr TH, Dearden S, Jenkins S, Brown H, et al. EGFR mutation detection in ctDNA from NSCLC patient plasma: a cross-platform comparison of leading technologies to support the clinical development of AZD9291. Lung Cancer 2015;90:509-15. https://doi.org/10.1016/j.lungcan.2015.10.004
  42. Wu SG, Chang YL, Yu CJ, Yang PC, Shih JY. Lung adenocarcinoma patients of young age have lower EGFR mutation rate and poorer efficacy of EGFR tyrosine kinase inhibitors. ERJ Open Res 2017;3:00092-2016.