非小细胞肺癌(NSCLC)治疗药物大全(2025)——提纲和解析

1.1 靶向治疗简述

1.2 首款NSCLC靶向药物

1.3 吉非替尼(易瑞沙)的简史

1.4 精准医疗

1.5 非小细胞肺癌(NSCLC)

1.6 FDA/NMPA批准/有逻辑的指南推荐/临床研究简述/临床试验药

1.6.1 EGFR敏感突变(EGFR 19DEL或L858R)[24个]

1.6.1.1 吉非替尼

1.6.1.2 埃克替尼(NMPA批准)

1.6.1.3 厄洛替尼

1.6.1.4 厄洛替尼+雷莫西尤单抗

1.6.1.5 厄洛替尼+贝伐珠单抗(NCCN指南)

1.6.1.6 阿法替尼

I. 药物推荐分级(EGFR非耐药突变)

1.6.1.7 阿法替尼+西妥昔单抗(NCCN指南提及)

1.6.1.8 达可替尼

1.6.1.9 奥希替尼

1.6.1.10 Olmutinib(MFDS批准)

1.6.1.11 阿美替尼(NMPA批准)

1.6.1.12 伏美替尼(NMPA批准)

1.6.1.13 贝福替尼(NMPA批准)

1.6.1.14 瑞齐替尼(NMPA批准)

1.6.1.15 瑞厄替尼(NMPA批准)

1.6.1.16 Lazertinib

1.6.1.17 利厄替尼(NMPA即将批准)

1.6.1.18 佐利替尼(NMPA批准)

1.6.1.19 BDTX-1535(临床试验)

1.6.1.20 德达博妥单抗(FDA即将批准)

1.6.1.21 Patritumab deruxtecan(FDA即将批准)

1.6.1.22 伦康依隆妥单抗(临床试验)

1.6.1.23 芦康沙妥珠单抗(NMPA即将批准该适应症)

1.6.1.24 SHR-A2009(临床试验)

II.药物推荐分级(EGFR敏感突变一线治疗)

1.6.2 EGFR 20INS[3个]

1.6.2.1 Amivantamab-vmjw

1.6.2.2 莫博赛替尼(已撤销适应症)

1.6.2.3 舒沃替尼(NMPA批准)

III.药物推荐分级(EGFR 20INS)

1.6.3 KRAS G12C[7个]

1.6.3.1 Sotorasib

1.6.3.2 Adagrasib

1.6.3.3 氟泽雷塞(NMPA批准)

1.6.3.4 格索雷塞(NMPA批准)

1.6.3.5 戈来雷塞(NMPA即将批准)

1.6.3.6 Divarasib(临床试验)

1.6.3.7 RMC-6291(临床试验)

IV.药物推荐分级(KRAS G12C二线治疗)

1.6.4 ALK重排/融合[9个]

1.6.4.1 克唑替尼

1.6.4.2 阿来替尼

1.6.4.3 塞瑞替尼

1.6.4.4 布格替尼

1.6.4.5 恩沙替尼

1.6.4.6 伊鲁阿克(NMPA批准)

1.6.4.7 依奉阿克(NMPA批准)

1.6.4.8 康太替尼(NMPA即将批准)

1.6.4.9 洛拉替尼

V.药物推荐分级(ALK融合一线治疗)

1.6.5 ROS1重排/融合[4个]

1.6.5.1 恩曲替尼

1.6.5.2 克唑替尼

1.6.5.3 瑞普替尼

1.6.5.4 塞瑞替尼(2025.V1 NCCN指南已删除)

1.6.5.5 洛拉替尼(NCCN指南)

1.6.5.6 安奈克替尼(NMPA批准)

1.6.5.7 他雷替尼(NMPA批准)

1.6.6 BRAF V600E[5个]

1.6.6.1 达拉非尼

1.6.6.2 曲美替尼

1.6.6.3 Encorafenib

1.6.6.4 Binimetinib

1.6.6.5 维莫非尼

1.6.7 NTRK融合/重排[1个]

1.6.7.1 恩曲替尼

1.6.7.2 拉罗替尼

1.6.7.3 瑞普替尼

1.6.8 MET 14号外显子跳变[5个]

1.6.8.1 卡马替尼

1.6.8.2 特泊替尼

1.6.8.3 克唑替尼(NCCN指南)

1.6.8.4 赛沃替尼(NMPA批准)

1.6.8.5 谷美替尼(NMPA批准)

1.6.8.6 伯瑞替尼(NMPA批准)

1.6.9 MET高水平扩增[1个]

1.6.9.1 卡马替尼(NCCN指南)

1.6.9.2 特泊替尼(NCCN指南)

1.6.9.3 克唑替尼(NCCN指南)

1.6.9.4 Telisotuzumab Vedotin(FDA即将获批)

1.6.10 RET重排/融合[3个]

1.6.10.1 塞普替尼

1.6.10.2 普拉替尼

1.6.10.3 Cabozantinib

1.6.11 ERBB2(HER2)突变[5个]

1.6.11.1 德曲妥珠单抗

1.6.11.2 恩美曲妥珠单抗(NCCN指南)

1.6.11.3 吡咯替尼(CSCO指南)

1.6.11.4 BAY 2927088(临床试验)

1.6.11.5 Zongertinib(临床试验)

1.6.12 NRG1融合[1个]

1.6.12.1 Zenocutuzumab

1.6.12.2 阿法替尼(案例报道)

1.6.13 FGFR突变[1个]

1.6.13.1 Erdafitinib

VI.药物推荐分级(HER2突变二线治疗)

1.6.14 抗血管生成类药物或多靶点激酶抑制剂[6个]

1.6.14.1 安罗替尼(NMPA批准)

1.6.14.2 Necitumumab

1.6.14.3 恩度(NMPA批准)

1.6.14.4 尼达尼布(EMA批准)

1.6.14.5 贝伐珠单抗

1.6.14.6 雷莫西尤单抗

2. 免疫治疗

2.1 免疫治疗的简单原理

2.2 首款NSCLC免疫治疗

2.3 FDA/NMPA批准

2.3.1 PD-1[9个]

2.3.1.1 帕博利珠单抗

2.3.1.2 纳武利尤单抗

2.3.1.3 Cemiplimab-rwlc

2.3.1.4 特瑞普利单抗(NMPA批准)

2.3.1.5 替雷利珠单抗(NMPA批准)

2.3.1.6 卡瑞利珠单抗(NMPA批准)

2.3.1.7 信迪利单抗(NMPA批准)

2.3.1.8 派安普利单抗(NMPA批准)

2.3.1.9 斯鲁利单抗(NMPA批准)

2.3.2 PD-L1[3个]

2.3.2.1 阿替利珠单抗

2.3.2.2 度伐利尤单抗

2.3.2.3 舒格利单抗(NMPA批准)

2.3.3 CTLA-4[2个]

2.3.3.1 伊匹木单抗

2.3.3.2 Tremelimumab

2.3.4 双抗[1个]

2.3.4.1 依沃西单抗(NMPA批准)

3. 其他治疗方案[1个]

3.1 TTFields(肿瘤电场治疗)

4. 化疗

4.1 化疗简述

4.2 NCCN指南的化疗方案

VII. 药物推荐分级(靶向阴性的药物治疗选择)

PD-L1检测不可及或成本过高

有PD-L1检测结果

5. 专题讨论

5.1 靶向治疗联合治疗的必要性、现状和未来

5.2 基因检测与NSCLC

5.3 头对头研究与挑战标准治疗

5.4 降低药物剂量，是否可行？

“史上最全”非小细胞肺癌(NSCLC)治疗药物大全(2024)

1.https://www.europeanpharmaceuticalreview.com/news/119270/fda-approves-tabrecta-for-treatment-of-metastatic-non-small-cell-lung-cancer/

2.非小细胞肺癌NCCN指南2025.V1

3.Passaro A, Leighl N, Blackhall F, Popat S, Kerr K, Ahn MJ, Arcila ME, Arrieta O, Planchard D, de Marinis F, Dingemans AM, Dziadziuszko R, Faivre-Finn C, Feldman J, Felip E, Curigliano G, Herbst R, Jänne PA, John T, Mitsudomi T, Mok T, Normanno N, Paz-Ares L, Ramalingam S, Sequist L, Vansteenkiste J, Wistuba II, Wolf J, Wu YL, Yang SR, Yang JCH, Yatabe Y, Pentheroudakis G, Peters S. ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer. Ann Oncol. 2022 May;33(5):466-487. doi: 10.1016/j.annonc.2022.02.003. Epub 2022 Feb 14. PMID: 35176458.[ESMO对于EGFR突变NSCLC的专家共识]

4.Owen DH, Ismaila N, Freeman-Daily J, Roof L, Singh N, Velazquez AI, Leighl NB. Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.1. J Clin Oncol. 2024 Jul 10;42(20):e44-e59. doi: 10.1200/JCO.24.00762. Epub 2024 May 30. PMID: 38815183.[ASCO动态指南驱动基因突变阳性2024.V1]

5.Bazhenova L, Ismaila N, Abu Rous F, Alluri K, Freeman-Daily J, Halmos B, Malhotra N, Marrone KA, Puri S, Qin A, Leighl NB. Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.2. J Clin Oncol. 2024 Dec 20;42(36):e72-e86. doi: 10.1200/JCO-24-02133. Epub 2024 Nov 12. PMID: 39531596.[ASCO动态指南驱动基因突变阳性2024.V2]

6.Jaiyesimi IA, Leighl NB, Ismaila N, Alluri K, Florez N, Gadgeel S, Masters G, Schenk EL, Schneider BJ, Sequist L, Singh N, Bazhenova L, Blanchard E, Freeman-Daily J, Furuya N, Halmos B, Azar IH, Kuruvilla S, Mullane M, Naidoo J, Reuss JE, Spigel DR, Owen DH, Patel JD. Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2023.3. J Clin Oncol. 2024 Apr 10;42(11):e23-e43. doi: 10.1200/JCO.23.02746. Epub 2024 Feb 28. PMID: 38417098.[ASCO动态指南驱动基因突变阴性2023.V3]

7.Megan E. Daly et al., Management of Stage III Non–Small Cell Lung Cancer: ASCO Guideline Rapid Recommendation Update. JCO 42, 3058-3060(2024).DOI:10.1200/JCO-24-01324

8.吉非替尼的故事

9.Nishimura T, Tada H, Nakagawa M, Teramukai S, Matsui S, Fukushima M. Lessons from gefitinib-induced interstitial lung disease in Japan: Problems in approval, pharmacovigilance, and regulatory decision-making procedures. Pharm Pract (Granada). 2006 Oct;4(4):168-78. doi: 10.4321/s1885-642x2006000400004. PMID: 25214906; PMCID: PMC4155619.

10.Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, Thongprasert S, Tan EH, Pemberton K, Archer V, Carroll K. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet. 2005 Oct 29-Nov 4;366(9496):1527-37. doi: 10.1016/S0140-6736(05)67625-8. PMID: 16257339.

11.Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. doi: 10.1056/NEJMoa0810699. Epub 2009 Aug 19. PMID: 19692680.

12.Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, Milenkova T. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014 Jan 7;110(1):55-62. doi: 10.1038/bjc.2013.721. Epub 2013 Nov 21. PMID: 24263064; PMCID: PMC3887309.

13.Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004 May 20;350(21):2129-39. doi: 10.1056/NEJMoa040938. Epub 2004 Apr 29. PMID: 15118073.

14.Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004 Jun 4;304(5676):1497-500. doi: 10.1126/science.1099314. Epub 2004 Apr 29. PMID: 15118125.

15.Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4. PMID: 38572751.

16.Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, Li L, Wei W, He J. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024 Feb 2;4(1):47-53. doi: 10.1016/j.jncc.2024.01.006. PMID: 39036382; PMCID: PMC11256708.

17.https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html

18.https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html

19.https://www.cancerresearchuk.org/about-cancer/lung-cancer/stages-types-grades/types

20.https://www.yalemedicine.org/conditions/non-small-cell-lung-cancer

21.Perez-Moreno P, Brambilla E, Thomas R, Soria JC. Squamous cell carcinoma of the lung: molecular subtypes and therapeutic opportunities. Clin Cancer Res. 2012 May 1;18(9):2443-51. doi: 10.1158/1078-0432.CCR-11-2370. Epub 2012 Mar 8. PMID: 22407829.

22.Saito M, Shiraishi K, Kunitoh H, Takenoshita S, Yokota J, Kohno T. Gene aberrations for precision medicine against lung adenocarcinoma. Cancer Sci. 2016 Jun;107(6):713-20. doi: 10.1111/cas.12941. Epub 2016 May 25. PMID: 27027665; PMCID: PMC4968599.

23.Chen P, Liu Y, Wen Y, Zhou C. Non-small cell lung cancer in China. Cancer Commun (Lond). 2022 Oct;42(10):937-970. doi: 10.1002/cac2.12359. Epub 2022 Sep 8. PMID: 36075878; PMCID: PMC9558689.

24.Gou LY, Wu YL. Prevalence of driver mutations in non-small-cell lung cancers in the People's Republic of China. Lung Cancer (Auckl). 2014 Feb 12;5:1-9. doi: 10.2147/LCTT.S40817. PMID: 28210137; PMCID: PMC5217505.

25.Hirsch FR, Suda K, Wiens J, Bunn PA Jr. New and emerging targeted treatments in advanced non-small-cell lung cancer. Lancet. 2016 Sep 3;388(10048):1012-24. doi: 10.1016/S0140-6736(16)31473-8. Epub 2016 Sep 1. PMID: 27598681.

26.Cooper AJ, Sequist LV, Lin JJ. Third-generation EGFR and ALK inhibitors: mechanisms of resistance and management. Nat Rev Clin Oncol. 2022 Aug;19(8):499-514. doi: 10.1038/s41571-022-00639-9. Epub 2022 May 9. Erratum in: Nat Rev Clin Oncol. 2022 Nov;19(11):744. doi: 10.1038/s41571-022-00680-8. PMID: 35534623; PMCID: PMC9621058.

27.Corvaja C, Passaro A, Attili I, Aliaga PT, Spitaleri G, Signore ED, de Marinis F. Advancements in fourth-generation EGFR TKIs in EGFR-mutant NSCLC: Bridging biological insights and therapeutic development. Cancer Treat Rev. 2024 Nov;130:102824. doi: 10.1016/j.ctrv.2024.102824. Epub 2024 Sep 4. PMID: 39366135.

28.Tannock IF, Pond GR, Booth CM. Biased Evaluation in Cancer Drug Trials-How Use of Progression-Free Survival as the Primary End Point Can Mislead. JAMA Oncol. 2022 May 1;8(5):679-680. doi: 10.1001/jamaoncol.2021.8206. PMID: 35266952.

29.Miyauchi E, Morita S, Nakamura A, Hosomi Y, Watanabe K, Ikeda S, Seike M, Fujita Y, Minato K, Ko R, Harada T, Hagiwara K, Kobayashi K, Nukiwa T, Inoue A; North-East Japan Study Group. Updated Analysis of NEJ009: Gefitinib-Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated EGFR. J Clin Oncol. 2022 Nov 1;40(31):3587-3592. doi: 10.1200/JCO.21.02911. Epub 2022 Aug 12. PMID: 35960896; PMCID: PMC9622660.

30.特罗凯NMPA说明书和FDA说明书

31.Yue D, Xu S, Wang Q, Li X, Shen Y, Zhao H, Chen C, Mao W, Liu W, Liu J, Zhang L, Ma H, Li Q, Yang Y, Liu Y, Chen H, Zhang Z, Zhang B, Wang C. 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 Dec 1;40(34):3912-3917. doi: 10.1200/JCO.22.00428. Epub 2022 Aug 26. PMID: 36027483.

32.Nakagawa K, Garon EB, Seto T, Nishio M, Ponce Aix S, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, Imamura F, Yoh K, Shih JY, Au KH, Moro-Sibilot D, Enatsu S, Zimmermann A, Frimodt-Moller B, Visseren-Grul C, Reck M; RELAY Study Investigators. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Dec;20(12):1655-1669. doi: 10.1016/S1470-2045(19)30634-5. Epub 2019 Oct 4. PMID: 31591063.

33.Nakagawa K, Garon EB, Seto T, Nishio M, Aix SP, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, Nishino K, Yoh K, Shih JY, Chik JY, Moro-Sibilot D, Puri T, Varughese SC, Frimodt-Moller B, Visseren-Grul C, Reck M. RELAY: Final Overall Survival for Erlotinib + Ramucirumab or Placebo in Untreated, EGFR-Mutated Metastatic NSCLC. J Thorac Oncol. 2024 Nov 30:S1556-0864(24)02495-X. doi: 10.1016/j.jtho.2024.11.032. Epub ahead of print. PMID: 39622410.

34.https://doi.org/10.1093/annonc/mdz260.002

35.Zhou Q, Xu CR, Cheng Y, Liu YP, Chen GY, Cui JW, Yang N, Song Y, Li XL, Lu S, Zhou JY, Ma ZY, Yu SY, Huang C, Shu YQ, Wang Z, Yang JJ, Tu HY, Zhong WZ, Wu YL. Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study. Cancer Cell. 2021 Sep 13;39(9):1279-1291.e3. doi: 10.1016/j.ccell.2021.07.005. Epub 2021 Aug 12. PMID: 34388377.

36.Kawashima Y, Fukuhara T, Saito H, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Seike M, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Bevacizumab plus erlotinib versus erlotinib alone in Japanese patients with advanced, metastatic, EGFR-mutant non-small-cell lung cancer (NEJ026): overall survival analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Respir Med. 2022 Jan;10(1):72-82. doi: 10.1016/S2213-2600(21)00166-1. Epub 2021 Aug 26. PMID: 34454653.

37.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 Sep;107(9):1179-86. doi: 10.1111/cas.12996. Epub 2016 Aug 9. PMID: 27323238; PMCID: PMC5021039.

38.Wang H, Lin L, Liang C, Pang J, Yin JC, Zhang J, Shao Y, Sun C, Guo R. Landscape of Concomitant Driver Alterations in Classical EGFR-Mutated Non-Small Cell Lung Cancer. JCO Precis Oncol. 2024 Aug;8:e2300520. doi: 10.1200/PO.23.00520. PMID: 39102631.

39.Cho JH, Lim SH, An HJ, Kim KH, Park KU, Kang EJ, Choi YH, Ahn MS, Lee MH, Sun JM, Lee SH, Ahn JS, Park K, Ahn MJ. 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 Feb 10;38(5):488-495. doi: 10.1200/JCO.19.00931. Epub 2019 Dec 11. PMID: 31825714; PMCID: PMC7098834.

40.Okuma Y, Kubota K, Shimokawa M, Hashimoto K, Kawashima Y, Sakamoto T, Wakui H, Murakami S, Okishio K, Hayashihara K, Ohe Y; Tokyo Cooperative Oncology Group (TCOG). First-Line Osimertinib for Previously Untreated Patients With NSCLC and Uncommon EGFR Mutations: The UNICORN Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2024 Jan 1;10(1):43-51. doi: 10.1001/jamaoncol.2023.5013. PMID: 37991747; PMCID: PMC10666043.

41.Janjigian YY, Smit EF, Groen HJ, Horn L, Gettinger S, Camidge DR, Riely GJ, Wang B, Fu Y, Chand VK, Miller VA, Pao W. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov. 2014 Sep;4(9):1036-45. doi: 10.1158/2159-8290.CD-14-0326. Epub 2014 Jul 29. PMID: 25074459; PMCID: PMC4155006.

42.Cheng Y, Mok TS, Zhou X, Lu S, Zhou Q, Zhou J, Du Y, Yu P, Liu X, Hu C, Lu Y, Zhang Y, Lee KH, Nakagawa K, Linke R, Wong CH, Tang Y, Zhu F, Wilner KD, Wu YL. Safety and efficacy of first-line dacomitinib in Asian patients with EGFR mutation-positive non-small cell lung cancer: Results from a randomized, open-label, phase 3 trial (ARCHER 1050). Lung Cancer. 2021 Apr;154:176-185. doi: 10.1016/j.lungcan.2021.02.025. Epub 2021 Feb 23. PMID: 33721611.

43.Ahn MJ, Tanaka K, Paz-Ares L, Cornelissen R, Girard N, Pons-Tostivint E, Vicente Baz D, Sugawara S, Cobo M, Pérol M, Mascaux C, Poddubskaya E, Kitazono S, Hayashi H, Hong MH, Felip E, Hall R, Juan-Vidal O, Brungs D, Lu S, Garassino M, Chargualaf M, Zhang Y, Howarth P, Uema D, Lisberg A, Sands J; TROPION-Lung01 Trial Investigators. Datopotamab Deruxtecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer: The Randomized, Open-Label Phase III TROPION-Lung01 Study. J Clin Oncol. 2024 Sep 9:JCO2401544. doi: 10.1200/JCO-24-01544. Epub ahead of print. PMID: 39250535.

44.Ma Y, Huang Y, Zhao Y, Zhao S, Xue J, Yang Y, Fang W, Guo Y, Han Y, Yang K, Li Y, Yang J, Fu Z, Chen G, Chen L, Zhou N, Zhou T, Zhang Y, Zhou H, Liu Q, Zhu Y, Zhu H, Xiao S, Zhang L, Zhao H. BL-B01D1, a first-in-class EGFR-HER3 bispecific antibody-drug conjugate, in patients with locally advanced or metastatic solid tumours: a first-in-human, open-label, multicentre, phase 1 study. Lancet Oncol. 2024 Jul;25(7):901-911. doi: 10.1016/S1470-2045(24)00159-1. Epub 2024 May 29. PMID: 38823410.

45.Wu YL, Zhou Q. Combination Therapy for EGFR-Mutated Lung Cancer. N Engl J Med. 2023 Nov 23;389(21):2005-2007. doi: 10.1056/NEJMe2311559. Epub 2023 Nov 8. PMID: 37937797.

46.Zwierenga F, van Veggel B, Hendriks LEL, Hiltermann TJN, Hiddinga BI, Hijmering Kappelle LBM, Ter Elst A, Hashemi SMS, Dingemans AC, van der Leest C, de Langen AJ, van den Heuvel MM, van der Wekken AJ. 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 Aug;170:133-140. doi: 10.1016/j.lungcan.2022.06.012. Epub 2022 Jun 23. PMID: 35777160.

47.Clinical Updates on RAS(ON) Inhibitors:Monotherapy and Combinations[RMC-6236的PPT]

48.Sotorasib Treatment Could Worsen the Prognosis of Advanced KRASG12C-Mutated Non-Small Cell Lung Cancer

49.Sacher A, LoRusso P, Patel MR, Miller WH Jr, Garralda E, Forster MD, Santoro A, Falcon A, Kim TW, Paz-Ares L, Bowyer S, de Miguel M, Han SW, Krebs MG, Lee JS, Cheng ML, Arbour K, Massarelli E, Choi Y, Shi Z, Mandlekar S, Lin MT, Royer-Joo S, Chang J, Dharia NV, Schutzman JL, Desai J; GO42144 Investigator and Study Group. Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation. N Engl J Med. 2023 Aug 24;389(8):710-721. doi: 10.1056/NEJMoa2303810. PMID: 37611121.

50.https://doi.org/10.1093/annonc/mdz260

51.https://clinicaltrials.gov/study/NCT02336451?tab=results

52.Shah M, Rahman A, Theoret MR, Pazdur R. The Drug-Dosing Conundrum in Oncology - When Less Is More. N Engl J Med. 2021 Oct 14;385(16):1445-1447. doi: 10.1056/NEJMp2109826. Epub 2021 Oct 9. PMID: 34623789.

53.Shaw AT, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, Mazieres J, Kim DW, Mok T, Polli A, Thurm H, Calella AM, Peltz G, Solomon BJ; CROWN Trial Investigators. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2020 Nov 19;383(21):2018-2029. doi: 10.1056/NEJMoa2027187. PMID: 33207094.

54.Solomon BJ, Bauer TM, Ignatius Ou SH, Liu G, Hayashi H, Bearz A, Penkov K, Wu YL, Arrieta O, Jassem J, Calella AM, Peltz G, Polli A, Thurm H, Mok T. Post Hoc Analysis of Lorlatinib Intracranial Efficacy and Safety in Patients With ALK-Positive Advanced Non-Small-Cell Lung Cancer From the Phase III CROWN Study. J Clin Oncol. 2022 Nov 1;40(31):3593-3602. doi: 10.1200/JCO.21.02278. Epub 2022 May 23. PMID: 35605188; PMCID: PMC9622589.

55.Solomon BJ, Liu G, Felip E, Mok TSK, Soo RA, Mazieres J, Shaw AT, de Marinis F, Goto Y, Wu YL, Kim DW, Martini JF, Messina R, Paolini J, Polli A, Thomaidou D, Toffalorio F, Bauer TM. Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study. J Clin Oncol. 2024 Oct 10;42(29):3400-3409. doi: 10.1200/JCO.24.00581. Epub 2024 May 31. PMID: 38819031; PMCID: PMC11458101.

56.Ignatius Ou SH, Solomon BJ, Besse B, Bearz A, Lin CC, Chiari R, Camidge DR, Lin JJ, Abbattista A, Toffalorio F, Soo RA. Brief Report: Final overall survival and long-term safety of lorlatinib in patients with ALK-positive non-small cell lung cancer from the pivotal phase 2 study. J Thorac Oncol. 2024 Nov 22:S1556-0864(24)02484-5. doi: 10.1016/j.jtho.2024.11.021. Epub ahead of print. PMID: 39581380.

57.Pacheco JM, Gao D, Smith D, Purcell T, Hancock M, Bunn P, Robin T, Liu A, Karam S, Gaspar L, Kavanagh B, Rusthoven C, Aisner D, Doebele R, Camidge DR. Natural History and Factors Associated with Overall Survival in Stage IV ALK-Rearranged Non-Small Cell Lung Cancer. J Thorac Oncol. 2019 Apr;14(4):691-700. doi: 10.1016/j.jtho.2018.12.014. Epub 2018 Dec 30. PMID: 30599201; PMCID: PMC7310567.

58.Garcia C, Abrahami D, Polli A, Chu H, Chandler C, Tan M, Kelton JM, Thomaidou D, Bauer T. Comparative Efficacy and Safety of Lorlatinib Versus Alectinib and Lorlatinib Versus Brigatinib for ALK-Positive Advanced/Metastatic NSCLC: Matching-Adjusted Indirect Comparisons. Clin Lung Cancer. 2024 Aug 13:S1525-7304(24)00158-X. doi: 10.1016/j.cllc.2024.08.003. Epub ahead of print. PMID: 39232917.

59.Drilon A, Camidge DR, Lin JJ, Kim SW, Solomon BJ, Dziadziuszko R, Besse B, Goto K, de Langen AJ, Wolf J, Lee KH, Popat S, Springfeld C, Nagasaka M, Felip E, Yang N, Velcheti V, Lu S, Kao S, Dooms C, Krebs MG, Yao W, Beg MS, Hu X, Moro-Sibilot D, Cheema P, Stopatschinskaja S, Mehta M, Trone D, Graber A, Sims G, Yuan Y, Cho BC; TRIDENT-1 Investigators. Repotrectinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2024 Jan 11;390(2):118-131. doi: 10.1056/NEJMoa2302299. PMID: 38197815.

60.https://news.abbvie.com/2023-11-29-AbbVie-Announces-Positive-Topline-Results-from-Phase-2-LUMINOSITY-Trial-Evaluating-Telisotuzumab-Vedotin-Teliso-V-for-Patients-with-Previously-Treated-Non-Small-Cell-Lung-Cancer-NSCLC

61.Subbiah V, Cassier PA, Siena S, Garralda E, Paz-Ares L, Garrido P, Nadal E, Vuky J, Lopes G, Kalemkerian GP, Bowles DW, Seetharam M, Chang J, Zhang H, Green J, Zalutskaya A, Schuler M, Fan Y, Curigliano G. Pan-cancer efficacy of pralsetinib in patients with RET fusion-positive solid tumors from the phase 1/2 ARROW trial. Nat Med. 2022 Aug;28(8):1640-1645. doi: 10.1038/s41591-022-01931-y. Epub 2022 Aug 12. PMID: 35962206; PMCID: PMC9388374.

62.Goto K, Goto Y, Kubo T, Ninomiya K, Kim SW, Planchard D, Ahn MJ, Smit EF, de Langen AJ, Pérol M, Pons-Tostivint E, Novello S, Hayashi H, Shimizu J, Kim DW, Kuo CH, Yang JC, Pereira K, Cheng FC, Taguchi A, Cheng Y, Feng W, Tsuchihashi Z, Jänne PA. Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic Non-Small-Cell Lung Cancer: Primary Results From the Randomized, Phase II DESTINY-Lung02 Trial. J Clin Oncol. 2023 Nov 1;41(31):4852-4863. doi: 10.1200/JCO.23.01361. Epub 2023 Sep 11. Erratum in: J Clin Oncol. 2024 Feb 1;42(4):485. doi: 10.1200/JCO.23.02574. Erratum in: J Clin Oncol. 2024 Oct 20;42(30):3635. doi: 10.1200/JCO-24-01883. PMID: 37694347; PMCID: PMC10617843.

63.Li BT, Smit EF, Goto Y, Nakagawa K, Udagawa H, Mazières J, Nagasaka M, Bazhenova L, Saltos AN, Felip E, Pacheco JM, Pérol M, Paz-Ares L, Saxena K, Shiga R, Cheng Y, Acharyya S, Vitazka P, Shahidi J, Planchard D, Jänne PA; DESTINY-Lung01 Trial Investigators. Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2022 Jan 20;386(3):241-251. doi: 10.1056/NEJMoa2112431. Epub 2021 Sep 18. PMID: 34534430; PMCID: PMC9066448.

64.Mazieres J, Lafitte C, Ricordel C, Greillier L, Negre E, Zalcman G, Domblides C, Madelaine J, Bennouna J, Mascaux C, Moro-Sibilot D, Pinquie F, Cortot AB, Otto J, Cadranel J, Langlais A, Morin F, Westeel V, Besse B. Combination of Trastuzumab, Pertuzumab, and Docetaxel in Patients With Advanced Non-Small-Cell Lung Cancer Harboring HER2 Mutations: Results From the IFCT-1703 R2D2 Trial. J Clin Oncol. 2022 Mar 1;40(7):719-728. doi: 10.1200/JCO.21.01455. Epub 2022 Jan 24. PMID: 35073148.

65.Cadranel J, Liu SV, Duruisseaux M, Branden E, Goto Y, Weinberg BA, Heining C, Schlenk RF, Cheema P, Jones MR, Drilon A, Trombetta D, Muscarella LA, Tolba K, Gounant V, Cseh A, Solca F, Laskin JJ, Renouf DJ. Therapeutic Potential of Afatinib in NRG1 Fusion-Driven Solid Tumors: A Case Series. Oncologist. 2021 Jan;26(1):7-16. doi: 10.1634/theoncologist.2020-0379. Epub 2020 Sep 23. PMID: 32852072; PMCID: PMC7794194.

66.Liu SV, Frohn C, Minasi L, Fernamberg K, Klink AJ, Gajra A, Savill KMZ, Jonna S. Real-world outcomes associated with afatinib use in patients with solid tumors harboring NRG1 gene fusions. Lung Cancer. 2024 Feb;188:107469. doi: 10.1016/j.lungcan.2024.107469. Epub 2024 Jan 5. PMID: 38219288.

67.贝伐珠单抗中文说明书

68.Reckamp KL, Redman MW, Dragnev KH, Minichiello K, Villaruz LC, Faller B, Al Baghdadi T, Hines S, Everhart L, Highleyman L, Papadimitrakopoulou V, Neal JW, Waqar SN, Patel JD, Gray JE, Gandara DR, Kelly K, Herbst RS. Phase II Randomized Study of Ramucirumab and Pembrolizumab Versus Standard of Care in Advanced Non-Small-Cell Lung Cancer Previously Treated With Immunotherapy-Lung-MAP S1800A. J Clin Oncol. 2022 Jul 20;40(21):2295-2306. doi: 10.1200/JCO.22.00912. Epub 2022 Jun 3. Erratum in: J Clin Oncol. 2022 Sep 1;40(25):3002. doi: 10.1200/JCO.22.01464. PMID: 35658002; PMCID: PMC9287284.

69.Dagher OK, Schwab RD, Brookens SK, Posey AD Jr. Advances in cancer immunotherapies. Cell. 2023 Apr 13;186(8):1814-1814.e1. doi: 10.1016/j.cell.2023.02.039. PMID: 37059073.

70.默沙东季报

71.Schoenfeld JD, Giobbie-Hurder A, Ranasinghe S, Kao KZ, Lako A, Tsuji J, Liu Y, Brennick RC, Gentzler RD, Lee C, Hubbard J, Arnold SM, Abbruzzese JL, Jabbour SK, Uboha NV, Stephans KL, Johnson JM, Park H, Villaruz LC, Sharon E, Streicher H, Ahmed MM, Lyon H, Cibuskis C, Lennon N, Jhaveri A, Yang L, Altreuter J, Gunasti L, Weirather JL, Mak RH, Awad MM, Rodig SJ, Chen HX, Wu CJ, Monjazeb AM, Hodi FS. Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy: an open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2022 Feb;23(2):279-291. doi: 10.1016/S1470-2045(21)00658-6. Epub 2022 Jan 13. PMID: 35033226; PMCID: PMC8813905.

72.Creelan BC, Wang C, Teer JK, Toloza EM, Yao J, Kim S, Landin AM, Mullinax JE, Saller JJ, Saltos AN, Noyes DR, Montoya LB, Curry W, Pilon-Thomas SA, Chiappori AA, Tanvetyanon T, Kaye FJ, Thompson ZJ, Yoder SJ, Fang B, Koomen JM, Sarnaik AA, Chen DT, Conejo-Garcia JR, Haura EB, Antonia SJ. Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial. Nat Med. 2021 Aug;27(8):1410-1418. doi: 10.1038/s41591-021-01462-y. Epub 2021 Aug 12. PMID: 34385708; PMCID: PMC8509078.

73.Pérol M, Felip E, Dafni U, Polito L, Pal N, Tsourti Z, Ton TGN, Merritt D, Morris S, Stahel R, Peters S. Effectiveness of PD-(L)1 inhibitors alone or in combination with platinum-doublet chemotherapy in first-line (1L) non-squamous non-small-cell lung cancer (Nsq-NSCLC) with PD-L1-high expression using real-world data. Ann Oncol. 2022 May;33(5):511-521. doi: 10.1016/j.annonc.2022.02.008. Epub 2022 Feb 23. PMID: 35218887.

74.Borghaei H, Ciuleanu TE, Lee JS, Pluzanski A, Caro RB, Gutierrez M, Ohe Y, Nishio M, Goldman J, Ready N, Spigel DR, Ramalingam SS, Paz-Ares LG, Gainor JF, Ahmed S, Reck M, Maio M, O'Byrne KJ, Memaj A, Nathan F, Tran P, Hellmann MD, Brahmer JR. Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. Ann Oncol. 2023 Feb;34(2):173-185. doi: 10.1016/j.annonc.2022.11.006. Epub 2022 Nov 19. PMID: 36414192.

75.Velcheti V, Rai P, Kao YH, Chirovsky D, Nunes AT, Liu SV. 5-Year Real-World Outcomes With Frontline Pembrolizumab Monotherapy in PD-L1 Expression ≥ 50% Advanced NSCLC. Clin Lung Cancer. 2024 Sep;25(6):502-508.e3. doi: 10.1016/j.cllc.2024.05.002. Epub 2024 May 16. PMID: 38880664.

76.Le X, Patel JD, Shum E, Baik C, Sanborn RE, Shu CA, Kim C, Fidler MJ, Hall R, Elamin YY, Tu J, Blumenschein G, Zhang J, Gibbons D, Gay C, Mohindra NA, Chae Y, Boumber Y, Sabari J, Santana-Davila R, Rogosin S, Herzberg B, Creelan B, Pellini B, Tanvetyanon T, Heeke S, Hernandez M, Gray JE, Saltos A, Heymach JV. A Multicenter Open-Label Randomized Phase II Study of Osimertinib With and Without Ramucirumab in Tyrosine Kinase Inhibitor-Naïve EGFR-Mutant Metastatic Non-Small Cell Lung Cancer (RAMOSE trial). J Clin Oncol. 2024 Oct 8:JCO2400533. doi: 10.1200/JCO.24.00533. Epub ahead of print. PMID: 39378386.

77.Maggie Liu SY, Huang J, Deng JY, Xu CR, Yan HH, Yang MY, Li YS, Ke EE, Zheng MY, Wang Z, Lin JX, Gan B, Zhang XC, Chen HJ, Wang BC, Tu HY, Yang JJ, Zhong WZ, Li Y, Zhou Q, Wu YL. PD-L1 expression guidance on sintilimab versus pembrolizumab with or without platinum-doublet chemotherapy in untreated patients with advanced non-small cell lung cancer (CTONG1901): A phase 2, randomized, controlled trial. Sci Bull (Beijing). 2024 Feb 26;69(4):535-543. doi: 10.1016/j.scib.2023.12.046. Epub 2023 Dec 26. PMID: 38185589.

78.Lim SM, Peters S, Ortega Granados AL, Pinto GDJ, Fuentes CS, Lo Russo G, Schenker M, Ahn JS, Reck M, Szijgyarto Z, Huseinovic N, Zografos E, Buss E, Stjepanovic N, O'Donnell S, de Marinis F. Dostarlimab or pembrolizumab plus chemotherapy in previously untreated metastatic non-squamous non-small cell lung cancer: the randomized PERLA phase II trial. Nat Commun. 2023 Nov 11;14(1):7301. doi: 10.1038/s41467-023-42900-4. PMID: 37951954; PMCID: PMC10640551.

79.Zhou, F., Guo, H., Xia, Y. et al. The changing treatment landscape of EGFR-mutant non-small-cell lung cancer. Nat Rev Clin Oncol (2024). https://doi.org/10.1038/s41571-024-00971-2

80.Lam DC, Liam CK, Andarini S, Park S, Tan DSW, Singh N, Jang SH, Vardhanabhuti V, Ramos AB, Nakayama T, Nhung NV, Ashizawa K, Chang YC, Tscheikuna J, Van CC, Chan WY, Lai YH, Yang PC. Lung Cancer Screening in Asia: An Expert Consensus Report. J Thorac Oncol. 2023 Oct;18(10):1303-1322. doi: 10.1016/j.jtho.2023.06.014. Epub 2023 Jun 28. PMID: 37390982.

81.Wheeler KJ, Roberts ME, Neiheisel MB. Medication adherence part two: predictors of nonadherence and adherence. J Am Assoc Nurse Pract. 2014 Apr;26(4):225-232. doi: 10.1002/2327-6924.12105. Epub 2014 Feb 12. PMID: 24574102.

82.Black Diamond Therapeutics于2024年9月23日公布的BDTX-1535新闻稿

83.ImmunityBio于2024年4月25日公布的Anktiva（nogapendekin alfa inbakicept）新闻稿

84.Owen DH, Singh N, Ismaila N, Blanchard E, Celano P, Florez N, Jain D, Leighl NB, Mamdani H, Masters G, Moffitt PR, Naidoo J, Phillips T, Riely GJ, Robinson AG, Schenk E, Schneider BJ, Sequist L, Spigel DR, Jaiyesimi IA. Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2022.2. J Clin Oncol. 2023 Feb 10;41(5):e1-e9. doi: 10.1200/JCO.22.02121. Epub 2022 Dec 19. PMID: 36534935.

85.https://www.fda.gov/

86.https://www.asco.org/

87.https://www.esmo.org/

88.https://wclc2024.iaslc.org/

89.https://www.nejm.org/

90.https://www.thelancet.com/

91.https://jamanetwork.com/

92.吉非替尼FDA说明书

93.https://www.fda.gov/drugs/resources-information-approved-drugs/fda-broadens-afatinib-indication-previously-untreated-metastatic-nsclc-other-non-resistant-egfr

94.https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-amivantamab-vmjw-carboplatin-and-pemetrexed-non-small-cell-lung-cancer-egfr-exon-19

95.奥希替尼 FLAURA2 2023 WCLC PPT

96.https://dailyreporter.esmo.org/european-lung-cancer-congress-2024/highlights-from-elcc-2024/post-progression-data-confirm-the-benefits-of-novel-combinations-for-egfr-mutated-nsclc

97.Planchard D, Jänne PA, Cheng Y, Yang JC, Yanagitani N, Kim SW, Sugawara S, Yu Y, Fan Y, Geater SL, Laktionov K, Lee CK, Valdiviezo N, Ahmed S, Maurel JM, Andrasina I, Goldman J, Ghiorghiu D, Rukazenkov Y, Todd A, Kobayashi K; FLAURA2 Investigators. Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC. N Engl J Med. 2023 Nov 23;389(21):1935-1948. doi: 10.1056/NEJMoa2306434. Epub 2023 Nov 8. PMID: 37937763.

98.RMC-6261关于NSCLC KRAS G12C的新闻稿

99.2020 WCLC摘要集

100.https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-unresectable-or-metastatic-her2

101.厄达替尼FDA说明书、

102.https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-erdafitinib-locally-advanced-or-metastatic-urothelial-carcinoma