Interpretation of updated NCCN guidelines for non-small cell lung cancer (version 1. 2021)_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHANG Jiahao ¹ , ZHANG Yajie ¹ ,  WANG Jie ² ,  LI Hecheng ¹

1. Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P.R.China;
2. Medical Oncology Department, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, 100021, P.R.China;

Corresponding author：

WANG Jie, Email: zlhuxi@163.com; LI Hecheng, Email: lihecheng2000@hotmail.com

Keywords：

Non-small cell lung cancer; NCCN guidelines; updates of version 1, 2021; interpretation of guideline

DOI：

10.7507/1007-4848.202012047

Video：

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Based on new clinical evidence, the National Comprehensive Cancer Network (NCCN) annually updates and releases the "NCCN Guidelines for the Clinical Diagnosis and Treatment of Non-Small Cell Lung Cancer" which has become the reference for clinical diagnosis and treatment approved and complied by clinicians worldwide. On November 25, 2020, the latest 2021 V1 version of "NCCN Clinical Diagnosis and Treatment Guidelines for Non-Small Cell Lung Cancer" (hereinafter referred to as "Guidelines") was released. Compared with the 8th edition of the "Guidelines" in 2020, many updates focused on the progress of targeted and immunotherapy. This article will provide the interpretations of the updated therapy content of this edition of the guidelines.

Citation： ZHANG Jiahao, ZHANG Yajie, WANG Jie, LI Hecheng. Interpretation of updated NCCN guidelines for non-small cell lung cancer (version 1. 2021). Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2021, 28(3): 271-277. doi: 10.7507/1007-4848.202012047 Copy

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2.	Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin, 2011, 61(2): 69-90.
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6.	Beaty BT, Weiner AA. Alternatives to surgery for early-stage non-small cell lung cancer: stereotactic radiotherapy. Clin Chest Med, 2020, 41(2): 185-195.
7.	Videtic GM, Paulus R, Singh AK, et al. Long-term follow-up on NRG Oncology RTOG 0915 (NCCTG N0927): A randomized phase 2 study comparing 2 stereotactic body radiation therapy schedules for medically inoperable patients with stage Ⅰ peripheral non-small cell lung cancer. Int J Radiat Oncol Biol Phys, 2019, 103(5): 1077-1084.
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9.	Nestle U, Schimek-Jasch T, Kremp S, et al. Imaging-based target volume reduction in chemoradiotherapy for locally advanced non-small-cell lung cancer (PET-Plan): A multicentre, open-label, randomised, controlled trial. Lancet Oncol, 2020, 21(4): 581-592.
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11.	Nguyen QN, Chun SG, Chow E, et al. Single-fraction stereotactic vs conventional multifraction radiotherapy for pain relief in patients with predominantly nonspine bone metastases: a randomized phase 2 trial. JAMA Oncol, 2019, 5(6): 872-878.
12.	Di Lisi D, Madonna R, Zito C, et al. Anticancer therapy-induced vascular toxicity: VEGF inhibition and beyond. Int J Cardiol, 2017, 227: 11-17.
13.	Palumbo VD, Fazzotta S, Fatica F, et al. Pancoast tumour: current therapeutic options. Clin Ter, 2019, 170(4): e291-e294.
14.	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.
15.	Wu YL, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med, 2020, 383(18): 1711-1723.
16.	Yang JCH, Kim SW, Kim DW, et al. Osimertinib in patients with epidermal growth factor receptor mutation-positive non-small-cell lung cancer and leptomeningeal metastases: The BLOOM Study. J Clin Oncol, 2020, 38(6): 538-547.
17.	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.
18.	Maemondo M, Tatsuro F, Haruhiro S, et al. NEJ026: Final overall survival analysis of bevacizumab plus erlotinib treatment for NSCLC patients harboring activating EGFR- mutations. J Clin Oncol, 2020, 38(15_suppl): 9506.
19.	Cortot AB, Kherrouche Z, Descarpentries C, et al. Exon 14 Deleted MET Receptor as a New Biomarker and Target in Cancers. J Natl Cancer Inst. 2017, 109(5). doi: 10.1093/jnci/djw262.
20.	Siena S, Doebele RC, Shaw AT, et al. Efficacy of entrectinib in patients (pts) with solid tumors and central nervous system (CNS) metastases: Integrated analysis from three clinical trials. J Clin Oncol, 2019, 37(15 Suppl): 3017.
21.	Planchard D, Kim TM, Mazieres J, et al. Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol, 2016, 17(5): 642-650.
22.	Planchard D, Besse B, Groen HJM, et al. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol, 2016, 17(7): 984-993.
23.	Smit E F, Nakagawa K, Nagasaka M, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): Interim results of DESTINY Lung01. J Clin Oncol, 2020, 38(15_suppl): 9504.
24.	Rusch VW, Giroux DJ, Kraut MJ, et al. Induction chemoradiation and surgical resection for superior sulcus non-small-cell lung carcinomas: long-term results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160). J Clin Oncol, 2007, 25(3): 313-318.
25.	Ando K, Kishino Y, Homma T, et al. Nivolumab plus ipilimumab versus existing immunotherapies in patients with PD-L1-positive advanced non-small cell lung cancer: A systematic review and network meta-analysis. Cancers (Basel), 2020, 12(7): 1905.
26.	Yasuda H, Park E, Yun CH, et al. Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer. Sci Transl Med, 2013, 5(216): 216ra177.
27.	Gergis C, Deepa R, Masanori F, et al. EGFR-A763_Y764insFQEA: A unique exon 20 insertion mutation that displays sensitivity to all classes of approved lung cancer EGFR tyrosine kinase inhibitors. J Clin Oncol, 2019, 37(15_suppl): e20593.
28.	Awad MM. Impaired c-Met receptor degradation mediated by MET Exon 14 mutations in non dmall-vell lung cancer. J Clin Oncol, 2016, 34(8): 879-881.
29.	Frampton GM, Ali SM, Rosenzweig M, et al. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov, 2015, 5(8): 850-859.
30.	Li Y, Gao L, Ma D, et al. Identification of MET exon14 skipping by targeted DNA- and RNA based next-generation sequencing in pulmonary sarcomatoid carcinomas. Lung Cancer, 2018, 122: 113-119.
31.	Michels S, Scheel AH, Scheffler M, et al. linicopathological characteristics of RET rearranged lung cancer in European patients. J Thorac Oncol, 2016, 11(1): 122-127.
32.	Ferrara R, Auger N, Auclin E, et al. Clinical and translational implications of RET rearrangements in non-small cell lung cancer. J Thorac Oncol, 2018, 13(1): 27-45.
33.	Farago F, Taylor MS, Doebele RC, et al. Clinicopathologic features of non-small-cell lung cancer harboring an NTRK gene fusion. JCO Precis Oncol, 2018, 2018: PO.18.00037.

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin, 2020, 70(1): 7-30.
2. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin, 2011, 61(2): 69-90.
3. NCCN clinical practice guidelines in oncology: non-small cell lung cancer (2021 version 1). (2020-11-25). URL: https://www.nccn.org/professionals/physician_gls/.
4. IJsseldijk MA, Shoni M, Siegert C, et al. Survival after stereotactic body radiation therapy for clinically diagnosed or biopsy-proven early-stage NSCLC: A systematic review and meta-analysis. J Thorac Oncol, 2019, 14(4): 583-595.
5. Maquilan G, Timmerman R. Stereotactic body radiation therapy for early-stage lung cancer. Cancer J, 2016, 22(4): 274-279.
6. Beaty BT, Weiner AA. Alternatives to surgery for early-stage non-small cell lung cancer: stereotactic radiotherapy. Clin Chest Med, 2020, 41(2): 185-195.
7. Videtic GM, Paulus R, Singh AK, et al. Long-term follow-up on NRG Oncology RTOG 0915 (NCCTG N0927): A randomized phase 2 study comparing 2 stereotactic body radiation therapy schedules for medically inoperable patients with stage Ⅰ peripheral non-small cell lung cancer. Int J Radiat Oncol Biol Phys, 2019, 103(5): 1077-1084.
8. Bezjak A, Paulus R, Gaspar LE, et al. Safety and efficacy of a five-fraction stereotactic body radiotherapy schedule for centrally located non-small-cell lung cancer: NRG Oncology/RTOG 0813 Trial. J Clin Oncol, 2019, 37(15): 1316-1325.
9. Nestle U, Schimek-Jasch T, Kremp S, et al. Imaging-based target volume reduction in chemoradiotherapy for locally advanced non-small-cell lung cancer (PET-Plan): A multicentre, open-label, randomised, controlled trial. Lancet Oncol, 2020, 21(4): 581-592.
10. Yuan S, Sun X, Li M, et al. A randomized study of involved-field irradiation versus elective nodal irradiation in combination with concurrent chemotherapy for inoperable stage Ⅲ nonsmall cell lung cancer. Am J Clin Oncol, 2007, 30(3): 239-244.
11. Nguyen QN, Chun SG, Chow E, et al. Single-fraction stereotactic vs conventional multifraction radiotherapy for pain relief in patients with predominantly nonspine bone metastases: a randomized phase 2 trial. JAMA Oncol, 2019, 5(6): 872-878.
12. Di Lisi D, Madonna R, Zito C, et al. Anticancer therapy-induced vascular toxicity: VEGF inhibition and beyond. Int J Cardiol, 2017, 227: 11-17.
13. Palumbo VD, Fazzotta S, Fatica F, et al. Pancoast tumour: current therapeutic options. Clin Ter, 2019, 170(4): e291-e294.
14. 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.
15. Wu YL, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med, 2020, 383(18): 1711-1723.
16. Yang JCH, Kim SW, Kim DW, et al. Osimertinib in patients with epidermal growth factor receptor mutation-positive non-small-cell lung cancer and leptomeningeal metastases: The BLOOM Study. J Clin Oncol, 2020, 38(6): 538-547.
17. 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.
18. Maemondo M, Tatsuro F, Haruhiro S, et al. NEJ026: Final overall survival analysis of bevacizumab plus erlotinib treatment for NSCLC patients harboring activating EGFR- mutations. J Clin Oncol, 2020, 38(15_suppl): 9506.
19. Cortot AB, Kherrouche Z, Descarpentries C, et al. Exon 14 Deleted MET Receptor as a New Biomarker and Target in Cancers. J Natl Cancer Inst. 2017, 109(5). doi: 10.1093/jnci/djw262.
20. Siena S, Doebele RC, Shaw AT, et al. Efficacy of entrectinib in patients (pts) with solid tumors and central nervous system (CNS) metastases: Integrated analysis from three clinical trials. J Clin Oncol, 2019, 37(15 Suppl): 3017.
21. Planchard D, Kim TM, Mazieres J, et al. Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol, 2016, 17(5): 642-650.
22. Planchard D, Besse B, Groen HJM, et al. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol, 2016, 17(7): 984-993.
23. Smit E F, Nakagawa K, Nagasaka M, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): Interim results of DESTINY Lung01. J Clin Oncol, 2020, 38(15_suppl): 9504.
24. Rusch VW, Giroux DJ, Kraut MJ, et al. Induction chemoradiation and surgical resection for superior sulcus non-small-cell lung carcinomas: long-term results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160). J Clin Oncol, 2007, 25(3): 313-318.
25. Ando K, Kishino Y, Homma T, et al. Nivolumab plus ipilimumab versus existing immunotherapies in patients with PD-L1-positive advanced non-small cell lung cancer: A systematic review and network meta-analysis. Cancers (Basel), 2020, 12(7): 1905.
26. Yasuda H, Park E, Yun CH, et al. Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer. Sci Transl Med, 2013, 5(216): 216ra177.
27. Gergis C, Deepa R, Masanori F, et al. EGFR-A763_Y764insFQEA: A unique exon 20 insertion mutation that displays sensitivity to all classes of approved lung cancer EGFR tyrosine kinase inhibitors. J Clin Oncol, 2019, 37(15_suppl): e20593.
28. Awad MM. Impaired c-Met receptor degradation mediated by MET Exon 14 mutations in non dmall-vell lung cancer. J Clin Oncol, 2016, 34(8): 879-881.
29. Frampton GM, Ali SM, Rosenzweig M, et al. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov, 2015, 5(8): 850-859.
30. Li Y, Gao L, Ma D, et al. Identification of MET exon14 skipping by targeted DNA- and RNA based next-generation sequencing in pulmonary sarcomatoid carcinomas. Lung Cancer, 2018, 122: 113-119.
31. Michels S, Scheel AH, Scheffler M, et al. linicopathological characteristics of RET rearranged lung cancer in European patients. J Thorac Oncol, 2016, 11(1): 122-127.
32. Ferrara R, Auger N, Auclin E, et al. Clinical and translational implications of RET rearrangements in non-small cell lung cancer. J Thorac Oncol, 2018, 13(1): 27-45.
33. Farago F, Taylor MS, Doebele RC, et al. Clinicopathologic features of non-small-cell lung cancer harboring an NTRK gene fusion. JCO Precis Oncol, 2018, 2018: PO.18.00037.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Interpretation of updated NCCN guidelines for non-small cell lung cancer (version 1. 2021)

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