EGFR敏感突变晚期非小细胞肺癌的靶向治疗进展
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摘要
肺癌是目前发生率和死亡率最高的恶性肿瘤之一。非小细胞肺癌(NSCLC)占肺癌总数的85%左右,其中约40%左右的患者存在表皮生长因子(EGFR)突变。表皮生长因子-酪氨酸激酶抑制剂(EGFR-TKIs)靶向治疗已经成为此类患者的一线标准治疗方案,但大多数患者不可避免地出现耐药问题。本文将对第1、2、3代EGFR-TKIs药物进行详细的总结,并阐述其与化疗或抗血管生成治疗的联用、免疫治疗在该类人群中的应用以及第1代EGFR-TKIs在辅助治疗方面应用的最新进展。
Lung cancer is one of the malignant tumors with the highest incidence and mortality. Non-small cell lung cancer(NSCLC) accounts for about 85% of the total number of lung cancer, and about 40% of the patients have epidermal growth factor receptor(EGFR) mutations. Targeted therapy with epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) has become the first-line standard treatment for these patients, but drug resistance inevitably appears in most patients. This review will summarize the first, second and third generation of EGFR-TKIs in detail, and elaborate its combination with chemotherapy and antiangiogenic therapy, the application of immunotherapy in this kind of population and the latest progress of the application of EGFR-TKI in adjuvant therapy.
Lung cancer is one of the malignant tumors with the highest incidence and mortality. Non-small cell lung cancer(NSCLC) accounts for about 85% of the total number of lung cancer, and about 40% of the patients have epidermal growth factor receptor(EGFR) mutations. Targeted therapy with epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) has become the first-line standard treatment for these patients, but drug resistance inevitably appears in most patients. This review will summarize the first, second and third generation of EGFR-TKIs in detail, and elaborate its combination with chemotherapy and antiangiogenic therapy, the application of immunotherapy in this kind of population and the latest progress of the application of EGFR-TKI in adjuvant therapy.
引文
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[23] 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[J].Lancet Oncol,2017,18(11):1454-1466.
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[25] Westover D,Zugazagoitia J,Cho BC,et al.Mechanisms of acquired resistance to first-and second-generation EGFR tyrosine kinase inhibitors[J].Ann Oncol,2018,29(Suppl 1):i10-i19.
[26] Mok TS,Wu YL,Ahn MJ,et al.Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer[J].N Engl J Med,2017,376(7):629-640.
[27] Soria JC,Ohe Y,Vansteenkiste J,et al.Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer[J].N Engl J Med,2018,378(2):113-125.
[28] Wu YL,Ahn MJ,Garassino MC,et al.CNS Efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer:data from a randomized phase III trial (AURA3)[J].J Clin Oncol,2018,36(26):2702-2709.
[29] Reungwetwattana T,Nakagawa K,Cho BC,et al.CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer[J/OL].J Clin Oncol,2018[2019-02-10].https://www.ncbi.nlm.nih.gov/pubmed/pmid/30153097.
[30] Ma Y,Zheng X,Zhao H,et al.First-in-human phase I study of AC0010,a mutant-selective EGFR inhibitor in non-small cell lung cancer:safety,efficacy,and potential mechanism of resistance[J].J Thorac Oncol,2018,13(7):968-977.
[31] Mok TSK,Kim SW,Wu YL,et al.Gefitinib plus chemotherapy versus chemotherapy in epidermal growth factor receptor mutation-positive non-small-cell lung cancer resistant to first-line gefitinib (IMPRESS):overall survival and biomarker analyses[J].J Clin Oncol,2017,35(36):4027-4034.
[32] Godzik-Spychalska J,Szyszka-Barth K,Spychalski L,et al.C-MET inhibitors in the treatment of lung cancer[J].Curr Treat Options Oncol,2014,15(4):670-682.
[33] Shi P,Oh YT,Zhang G,et al.Met gene amplification and protein hyperactivation is a mechanism of resistance to both first and third generation EGFR inhibitors in lung cancer treatment[J].Cancer Lett,2016,380(2):494-504.
[34] Wu YL,Zhang L,Kim DW,et al.Phase Ib/II study of capmatinib (INC280) plus gefitinib after failure of epidermal growth factor receptor (EGFR) inhibitor therapy in patients with EGFR-mutated,MET factor-dysregulated non-small-cell lung cancer[J].J Clin Oncol,2018,36(31):3101-3109.
[35] Cheng Y,Zhou J,Lu S,et al.Phase 2 study of tepotinib+gefitinib in met-positive/epidermal growth factor receptor-mutant NSCLC[EB/OL].ESMO Congress 2018,2018[2019-02-10].http://www.liangyihui.net/doc/46659.
[36] Marcoux N,Gettinger SN,O'Kane G,et al.EGFR-mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas:clinical outcomes[J/OL].J Clin Oncol,2019[2019-02-10].https://www.x-mol.com/paper/930650.
[37] Kim TM,Song A,Kim DW,et al.Mechanisms of acquired resistance to AZD9291:A mutation-selective,irreversible EGFR inhibitor[J].J Thorac Oncol,2015,10(12):1736-1744.
[38] Niederst MJ,Hu H,Mulvey HE,et al.The allelic context of the C797S mutation acquired upon treatment with third-generation EGFR inhibitors impacts sensitivity to subsequent treatment strategies[J].Clin Cancer Res,2015,21(17):3924-3933.
[39] Papadimitrakopoulou V,Wu YL,Han JY,et al.Analysis of resistance mechanisms to osimertinib in patients with EGFR T790M advanced NSCLC from the AURA3 study[J].Ann Oncol,2019,29(Suppl 8):aLBA51.
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