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Update on Adjuvant Treatment in Resectable Non-Small Cell Lung Cancer and Potential Biomarkers Predicting Postoperative Relapse

  • Jeong Uk Lim (Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
  • 투고 : 2022.05.16
  • 심사 : 2022.10.21
  • 발행 : 2023.01.31

초록

A significant proportion of patients with non-small cell lung cancer (NSCLC) is diagnosed in the early and resectable stage. Despite the use of platinum-based adjuvant chemotherapy, there was only a marginal increase in overall survival and a 15% decrease in relapse. With the advents of immunotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), the landscape of adjuvant treatment in completely resectable NSCLC is changing. Postoperative radiotherapy can be beneficial to patients who underwent surgical resection in certain clinical settings. In addition, new biomarkers that predict efficacy of EGFR TKI and immunotherapy as adjuvant treatment are also necessary. In this review, recent updates in adjuvant treatment in resectable NSCLC were briefly explained.

키워드

참고문헌

  1. Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt WE, et al. The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (Eighth) edition of the TNM classification for lung cancer. J Thorac Oncol 2016;11:39-51. https://doi.org/10.1016/j.jtho.2015.09.009
  2. Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE collaborative group. J Clin Oncol 2008;26:3552-9. https://doi.org/10.1200/JCO.2007.13.9030
  3. Uramoto H, Tanaka F. Recurrence after surgery in patients with NSCLC. Transl Lung Cancer Res 2014;3:242-9.
  4. Kojima K, Sakamoto T, Kasai T, Kagawa T, Yoon H, Atagi S. PD-L1 expression as a predictor of postoperative recurrence and the association between the PD-L1 expression and EGFR mutations in NSCLC. Sci Rep 2021;11:17522.
  5. Pisters KM, Le Chevalier T. Adjuvant chemotherapy in completely resected non-small-cell lung cancer. J Clin Oncol 2005;23:3270-8. https://doi.org/10.1200/JCO.2005.11.478
  6. Goss GD, O'Callaghan C, Lorimer I, Tsao MS, Masters GA, Jett J, et al. Gefitinib versus placebo in completely resected non-small-cell lung cancer: results of the NCIC CTG BR19 study. J Clin Oncol 2013;31:3320-6. https://doi.org/10.1200/JCO.2013.51.1816
  7. Kelly K, Altorki NK, Eberhardt WE, O'Brien ME, Spigel DR, Crino L, et al. Adjuvant erlotinib versus placebo in patients with stage IB-IIIA non-small-cell lung cancer (RADIANT): a randomized, double-blind, phase III trial. J Clin Oncol 2015;33:4007-14. https://doi.org/10.1200/JCO.2015.61.8918
  8. Pennell NA, Neal JW, Chaft JE, Azzoli CG, Janne PA, Govindan R, et al. SELECT: a phase II trial of adjuvant erlotinib in patients with resected epidermal growth factor receptor-mutant non-small-cell lung cancer. J Clin Oncol 2019;37:97-104. https://doi.org/10.1200/JCO.18.00131
  9. Wu YL, Zhong W, Wang Q, Mao W, Xu ST, Wu L, et al. CTONG1104: Adjuvant gefitinib versus chemotherapy for resected N1-N2 NSCLC with EGFR mutation: final overall survival analysis of the randomized phase III trial 1 analysis of the randomized phase III trial. J Clin Oncol 2020;38(15 suppl):9005.
  10. Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Shen Y, et al. 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;19:139-48. https://doi.org/10.1016/S1470-2045(17)30729-5
  11. Wu YL, Tsuboi M, He J, John T, Grohe C, Majem M, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med 2020;383:1711-23. https://doi.org/10.1056/NEJMoa2027071
  12. Remon J, Hendriks LE. Osimertinib should be the standard of care for the adjuvant therapy of stage IB to IIIA EGFR-mutant NSCLC. J Thorac Oncol 2021;16:368-70. https://doi.org/10.1016/j.jtho.2020.11.027
  13. Uprety D. Osimertinib should not yet be considered the standard of care for EGFR-mutant NSCLC in the adjuvant setting. J Thorac Oncol 2021;16:371-4. https://doi.org/10.1016/j.jtho.2020.12.003
  14. Solomon BJ, Ahn JS, Barlesi F, Dziadziuszko R, Nishio M, Shaw AT, et al. ALINA: A phase III study of alectinib versus chemotherapy as adjuvant therapy in patients with stage IB-IIIA anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). J Clin Oncol 2019;37(15 suppl):TPS8569.
  15. Felip E, Altorki N, Zhou C, Csoszi T, Vynnychenko I, Goloborodko O, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet 2021;398:1344-57. https://doi.org/10.1016/S0140-6736(21)02098-5
  16. Pisters K, Kris MG, Gaspar LE, Ismaila N; Adjuvant Systemic Therapy and Adjuvant Radiation Therapy for Stage I to IIIA NSCLC Guideline Expert Panel. Adjuvant systemic therapy and adjuvant radiation therapy for stage I-IIIA completely resected non-small-cell lung cancer: ASCO guideline rapid recommendation update. J Clin Oncol 2022;40:1127-9. https://doi.org/10.1200/JCO.22.00051
  17. ClinicalTrials.gov. Study of Pembrolizumab (MK-3475) vs Placebo for Participants With Non-small Cell Lung Cancer After Resection With or Without Standard Adjuvant Therapy (MK-3475-091/KEYNOTE-091) (PEARLS) [Internet]. Bethesda: U.S. National Library of Medicine; 2020 [cited 2022 Nov 30]. Available from: https://clinicaltrials. gov/ct2/show/NCT02504372.
  18. Paz-Ares L, O'Brien MER, Mauer M, Dafni U, Oselin K, Havel L, et al. VP3-2022: Pembrolizumab (pembro) versus placebo for early-stage non-small cell lung cancer (NSCLC) following complete resection and adjuvant chemotherapy (chemo) when indicated: randomized, triple-blind, phase III EORTC-1416-LCG/ETOP 8-15-PEARLS/KEY-NOTE-091 study. Ann Oncol 2022;33:451-3. https://doi.org/10.1016/j.annonc.2022.02.224
  19. ClinicalTrials.gov. Efficacy and Safety of Pembrolizumab (MK-3475) With Platinum Doublet Chemotherapy as Neoadjuvant/Adjuvant Therapy for Participants With Resectable Stage II, IIIA, and Resectable IIIB (T3-4N2) Nonsmall Cell Lung Cancer (MK-3475-671/KEYNOTE-671) [Internet]. Bethesda: U.S. National Library of Medicine; 2022 [cited 2022 Nov 30]. Available from: https://ClinicalTrials.gov/show/NCT03425643.
  20. ClinicalTrials.gov. Nivolumab After Surgery and Chemotherapy in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer (An ALCHEMIST Treatment Trial) (ANVIL) [Internet]. Bethesda: U.S. National Library of Medicine; 2022 [cited 2022 Nov 30]. Available from: https://clinicaltrials.gov/ct2/show/NCT02595944.
  21. Lally BE, Geiger AM, Urbanic JJ, Butler JM, Wentworth S, Perry MC, et al. Trends in the outcomes for patients with limited stage small cell lung cancer: an analysis of the surveillance, epidemiology, and end results database. Lung Cancer 2009;64:226-31. https://doi.org/10.1016/j.lungcan.2008.08.010
  22. Lally BE, Zelterman D, Colasanto JM, Haffty BG, Detterbeck FC, Wilson LD. Postoperative radiotherapy for stage II or III non-small-cell lung cancer using the surveillance, epidemiology, and end results database. J Clin Oncol 2006;24:2998-3006. https://doi.org/10.1200/JCO.2005.04.6110
  23. Dai H, Hui Z, Ji W, Liang J, Lu J, Ou G, et al. Postoperative radiotherapy for resected pathological stage IIIA-N2 nonsmall cell lung cancer: a retrospective study of 221 cases from a single institution. Oncologist 2011;16:641-50. https://doi.org/10.1634/theoncologist.2010-0343
  24. Robinson CG, Patel AP, Bradley JD, DeWees T, Waqar SN, Morgensztern D, et al. Postoperative radiotherapy for pathologic N2 non-small-cell lung cancer treated with adjuvant chemotherapy: a review of the national cancer data base. J Clin Oncol 2015;33:870-6. https://doi.org/10.1200/JCO.2014.58.5380
  25. Zhang CC, Hou RP, Xia WY, Zeng WQ, Liu J, Wang JM, et al. Prognostic index for estimating the survival benefit of postoperative radiotherapy in pathologic N2 non-small cell lung cancer: a real-world validation study. Lung Cancer 2021;156:100-8. https://doi.org/10.1016/j.lungcan.2021.04.009
  26. Le Pechoux C, Pourel N, Barlesi F, Lerouge D, Antoni D, Lamezec B, et al. Postoperative radiotherapy versus no postoperative radiotherapy in patients with completely resected non-small-cell lung cancer and proven mediastinal N2 involvement (Lung ART): an open-label, randomised, phase 3 trial. Lancet Oncol 2022;23:104-14. https://doi.org/10.1016/S1470-2045(21)00606-9
  27. Hui Z, Men Y, Hu C, Kang J, Sun X, Bi N, et al. Effect of postoperative radiotherapy for patients with pIIIA-N2 non-small cell lung cancer after complete resection and adjuvant chemotherapy: the phase 3 PORT-C randomized clinical trial. JAMA Oncol 2021;7:1178-85. https://doi.org/10.1001/jamaoncol.2021.1910
  28. Liu J, Ladbury C, Kim J, Raz D, Erhunmwunsee L, West HJ, et al. Postoperative radiation therapy should be used for completely resected stage III-N2 NSCLC in select patients. J Thorac Oncol 2022;17:194-6. https://doi.org/10.1016/j.jtho.2021.08.006
  29. Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med 2018;378:158-68. https://doi.org/10.1056/NEJMra1703481
  30. Wang PF, Chen Y, Song SY, Wang TJ, Ji WJ, Li SW, et al. Immune-related adverse events associated with anti-PD-1/PD-L1 treatment for malignancies: a meta-analysis. Front Pharmacol 2017;8:730.
  31. Min JW, Lim JU. Immune checkpoint inhibitors in patients with chronic kidney disease: assessing their ability to cause acute kidney injury and informing their proper use. Semin Oncol 2022;49:141-7. https://doi.org/10.1053/j.seminoncol.2022.01.012
  32. Kim S, Lim JU. Immune checkpoint inhibitor-related interstitial lung disease in patients with advanced non-small cell lung cancer: systematic review of characteristics, incidence, risk factors, and management. J Thorac Dis 2022;14:1684-95. https://doi.org/10.21037/jtd-22-93
  33. Hoa S, Laaouad L, Roberts J, Ennis D, Ye C, Al Jumaily K, et al. Preexisting autoimmune disease and immune-related adverse events associated with anti-PD-1 cancer immunotherapy: a national case series from the Canadian Research Group of Rheumatology in Immuno-Oncology. Cancer Immunol Immunother 2021;70:2197-207. https://doi.org/10.1007/s00262-021-02851-5
  34. Lally BE, Detterbeck FC, Geiger AM, Thomas CR, Machtay M, Miller AA, et al. The risk of death from heart disease in patients with nonsmall cell lung cancer who receive postoperative radiotherapy: analysis of the Surveillance, Epidemiology, and End Results database. Cancer 2007;110:911-7. https://doi.org/10.1002/cncr.22845
  35. Zhang H, Zhang DX, Ju T, Zhou J. The effect of postoperative radiotherapy on the survival of patients with resectable stage III-N2 non-small-cell lung cancer: a systematic review and meta-analysis. Neoplasma 2019;66:717-26. https://doi.org/10.4149/neo_2018_181213N965
  36. Wakelee HA, Stephenson P, Keller SM, Wagner H, Herskovic A, Komaki R, et al. Post-operative radiotherapy (PORT) or chemoradiotherapy (CPORT) following resection of stages II and IIIA non-small cell lung cancer (NSCLC) does not increase the expected risk of death from intercurrent disease (DID) in Eastern Cooperative Oncology Group (ECOG) trial E3590. Lung Cancer 2005;48: 389-97. https://doi.org/10.1016/j.lungcan.2004.11.007
  37. Chun SG, Hu C, Choy H, Komaki RU, Timmerman RD, Schild SE, et al. Impact of intensity-modulated radiation therapy technique for locally advanced non-small-cell lung cancer: a secondary analysis of the NRG oncology RTOG 0617 randomized clinical trial. J Clin Oncol 2017;35:56-62. https://doi.org/10.1200/JCO.2016.69.1378
  38. Suveg K, Plasswilm L, Iseli T, Leskow P, Fischer GF, Putora PM. Role of adjuvant radiotherapy in non-small cell lung cancer-a review. Cancers (Basel) 2022;14:1617.
  39. Diaz LA, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol 2014;32:579-86. https://doi.org/10.1200/JCO.2012.45.2011
  40. Pradhan M, Chocry M, Gibbons DL, Sepesi B, Cascone T. Emerging biomarkers for neoadjuvant immune checkpoint inhibitors in operable non-small cell lung cancer. Transl Lung Cancer Res 2021;10:590-606. https://doi.org/10.21037/tlcr-20-573
  41. Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature 2017;545:446-51. https://doi.org/10.1038/nature22364
  42. Qiu B, Guo W, Zhang F, Lv F, Ji Y, Peng Y, et al. Dynamic recurrence risk and adjuvant chemotherapy benefit prediction by ctDNA in resected NSCLC. Nat Commun 2021;12:6770.
  43. de Miguel-Perez D, Bayarri-Lara CI, Ortega FG, Russo A, Moyano Rodriguez MJ, Alvarez-Cubero MJ, et al. Post-surgery circulating tumor cells and AXL overexpression as new poor prognostic biomarkers in resected lung adenocarcinoma. Cancers (Basel) 2019;11:1750.
  44. Tsakonas G, Botling J, Micke P, Rivard C, LaFleur L, Mattsson J, et al. c-MET as a biomarker in patients with surgically resected non-small cell lung cancer. Lung Cancer 2019;133:69-74. https://doi.org/10.1016/j.lungcan.2019.04.028
  45. Fu F, Zhang Y, Gao Z, Zhao Y, Wen Z, Han H, et al. Combination of CD47 and CD68 expression predicts survival in Eastern-Asian patients with non-small cell lung cancer. J Cancer Res Clin Oncol 2021;147:739-47. https://doi.org/10.1007/s00432-020-03477-3
  46. Mony JT, Schuchert MJ. Prognostic implications of heterogeneity in intra-tumoral immune composition for recurrence in early stage lung cancer. Front Immunol 2018;9:2298.
  47. Chaft JE, Dahlberg SE, Khullar OV, Edelman MJ, Simone CB, Heymach J, et al. EA5142 adjuvant nivolumab in resected lung cancers (ANVIL). J Clin Oncol 2018;36(15 suppl):TPS8581.