Progress and prospect of epidermal growth factor receptor tyrosine kinase inhibitor in treatment of non-small cell lung cancer

Hanshui JIANG; Guoming WU

doi:10.16016/j.2097-0927.202209158

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Progress and prospect of epidermal growth factor receptor tyrosine kinase inhibitor in treatment of non-small cell lung cancer

Monographic Reports: Targeted therapy of lung cancer | 更新时间：2026-01-09

- Progress and prospect of epidermal growth factor receptor tyrosine kinase inhibitor in treatment of non-small cell lung cancer
- Journal of Army Medical University Vol. 44, Issue 24, Pages: 2445-2452(2022)
- 作者机构：
  
  310042 杭州, 浙江省杭州市树兰(杭州)医院呼吸与危重症医学科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.2097-0927.202209158
  CLC： R734.2;R979.19
- Received：17 September 2022，
  
  Revised：2022-11-16，
  
  Published：30 December 2022
- 稿件说明：
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Hanshui JIANG, Guoming WU. Progress and prospect of epidermal growth factor receptor tyrosine kinase inhibitor in treatment of non-small cell lung cancer[J]. Journal of Army Medical University, 2022, 44(24): 2445-2452.
DOI：

Hanshui JIANG, Guoming WU. Progress and prospect of epidermal growth factor receptor tyrosine kinase inhibitor in treatment of non-small cell lung cancer[J]. Journal of Army Medical University, 2022, 44(24): 2445-2452. DOI： 10.16016/j.2097-0927.202209158.

摘要

表皮生长因子受体(epidermal growth factor receptor，EGFR)突变是我国晚期非小细胞肺癌(non-small cell lung cancer，NSCLC)最常见的驱动基因，EGFR络氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor，EGFR-TKI)已经成为其最主要的和首选的治疗方式。EGFR敏感突变主要包括19号外显子缺失(19

Del

)突变和21号外显子

858

突变，约占EGFR突变的90%，而19

Del

亚型对EGFR-TKI更加敏感和有效。对于EGFR敏感突变的晚期NSCLC患者选择任何一种在我国已经获得一线适应症的EGFR-TKI作为一线治疗都是规范的和合理的，其中奥希替尼是较优的选择。奥希替尼在早中期NSCLC术后的辅助治疗已经获得突破性进展，大大降低了疾病复发或死亡风险。未来在EGFR通路的研究重点将聚焦于克服EGFR-TKI耐药性，EGFR罕见突变抑制剂的研发和新辅助靶向治疗等。

Abstract

Epidermal growth factor receptor (EGFR) is the most common driver gene of mutations in advanced non-small cell lung cancer (NSCLC)

and EGFR tyrosine kinase inhibitor (EGFR-TKI) has become the most important and preferred treatment. EGFR-sensitive mutations mainly consist of exon 19 deletion (

19Del

) mutation and exon 21

858

mutation

accounting for about 90% of EGFR mutations

while the 19

Del

subtype is more sensitive and effective to EGFR-TKI. For advanced NSCLC patients with EGFR-sensitive mutations

it is standard and reasonable to select any EGFR-TKI which has been given first-line indications in our country as first-line treatment

among which osimertinib is a better choice. Osimertinib has made a breakthrough in the adjuvant treatment for early- and middle-stage NSCLC

and greatly reduced the risk of disease recurrence or death. Researches on EGFR pathway will focus on overcoming EGFR-TKI resistance

development of EGFR rare mutation inhibitors and neoadjuvant targeted therapy.

关键词

Keywords

references

DATTA D, LAHIRI B. Preoperative evaluation of patients undergoing lung resection surgery[J]. Chest, 2003, 123(6): 2096-2103. DOI: 10.1378/chest.123.6.2096.

BURDETT S, PIGNON J P, TIERNEY J, et al . Adjuvant chemo- therapy for resected early-stage non-small cell lung cancer[J ] . Cochrane Database Syst Rev, 2015, (3):CD011430. DOI: 10.1002/14651858.CD011430.

APPERT-COLLIN A, HUBERT P, CRÉMEL G, et al . Role of ErbB receptors in cancer cell migration and invasion[J ] . Front Pharmacol, 2015, 6: 283. DOI: 10.3389/fphar.2015.00283.

中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会(CSCO)非小细胞肺癌诊疗指南[M]. 北京: 人民卫生出版社, 2022: 96.

Chinese Society of Clinical Oncology Guideline Working Committee. Guidelines of Chinese Society of Clinical Oncology(CSCO)Non-Small Cell Lung Cancer[M]. Beijing: People's Medical Publishing House(PMPH), 2022: 96.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Non-Small Cell Lung Cancer, Version 3. 2022.

ZHANG Y L, YUAN J Q, WANG K F, et al . The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis[J ] . Oncotarget, 2016, 7(48): 78985-78993. DOI: 10.18632/oncotarget.12587.

ROBICHAUX J P, LE X N, VIJAYAN R S K, et al . Structure-based classification predicts drug response in EGFR-mutant NSCLC[J ] . Nature, 2021, 597(7878): 732-737. DOI: 10.1038/s41586-021-03898-1.

KOBAYASHI Y, MITSUDOMI T. Not all epidermal growth factor receptor mutations inlung cancer are created equal: perspectives for individualized treatment strategy[J]. Cancer Sci, 2016, 107(9): 1179-1186. DOI: 10.1111/cas.12996.

MOK T S, WU Y L, THONGPRASERT S, et al . Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma[J ] . N Engl J Med, 2009, 361(10): 947-957. DOI: 10.1056/nejmoa0810699.

ZHOU C, WU Y L, CHEN G, et al . Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study[J ] . Lancet Oncol. 2011, 12(8): 735-742. DOI: 10.1016/S1470-2045(11)70184-X

PARK K, TAN E H, O'BYRNE K, et al . Afati nib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial[J ] . Lancet Oncol, 2016, 17(5): 577-589. DOI: 10.1016/S1470-2045(16)30033-X.

SORIA J C, 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. DOI: 10.1056/NEJMoa1713137.

ZHAO F N, ZHAO Y Q, HAN L Z, et al . Clinicoradiological features associated with epidermal growthfactor receptor exon 19 and 21 mutation in lung adenocarcinoma[J ] . Clin Radiol, 2019, 74(1): 80. e7-80.80. e17. DOI: 10.1016/j.crad.2018.10.001.

SHEN Y C, TSENG G C, TU C Y, et al . Comparing the effects of afatinib with gefitinib or Erlotinib in patients with advanced-stage lung adenocarcinoma harboring non-classical epidermal growth factor receptor mutations[J ] . Lung Cancer, 2017, 110: 56-62. DOI: 10.1016/j.lungcan.2017.06.007.

WU Y L, SAIJO N, THONGPRASERT S, et al . Efficacy according to blind independent central review: post-hoc analyses from the phase Ⅲ, randomized, multicenter, IPASS study of first-line gefitinib versus carboplatin/paclitaxel in Asian patients with EGFR mutation-positive advanced N SCLC[J ] . Lung Cancer, 2017, 104: 119-125. DOI: 10.1016/j.lungcan.2016.11.022.

SHI Y K, WANG L, HAN B H, et al . First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study[J ] . Ann Oncol, 2017, 28(10): 2443-2450. DOI: 10.1093/annonc/mdx359.

PAZ-ARES L, TAN E H, O'BYRNE K, et al . Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase Ⅱb LUX-Lung 7 trial[J ] . Ann Oncol, 2017, 28(2): 270-277. DOI: 10.1093/annonc/mdw611.

WU Y L, CHENG Y, ZHOU X D, 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. DOI: 10.1016/S1470-2045(17)30608-3.

MOK T S, CHENG Y, ZHOU X D, et al . Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non-small-cell lung cancer and EGFR -activating mutations[J ] . J Clin Oncol, 2018, 36(22): 2244-2250. DOI: 10.1200/jco.2018.78.7994..

RAMALINGAM S S, VANSTEENKISTE J, PLANCHARD D, et al . Overall survival with osimertinib in untreated, EGFR -mutated advanced NSCLC[J ] . N Engl J Med, 2020, 382(1): 41-50. DOI: 10.1056/nejmoa1913662..

LU S, DONG X, JIAN H, et al . AENEAS: A randomized phase Ⅲ trial of aumolertinib versus gefitinib as first-line therapy for locally advanced or metastatic non-small-cell lung cancer with EGFR exon 19 deletion or L 858 R mutations[J ] . J Clin Oncol. 2022, 40(27): 3162-3171. DOI: 10.1200/JCO.21.02641.

SHI Y K, CHEN G Y, WANG X, et al . Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study[J ] . Lancet Respir Med, 2022, 10(11): 1019-1028. DOI: 10.1016/S2213-2600(22)00168-0.

YANG J C H, SEQUIST L V, GEATER S L, et al . Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6[J ] . Lancet Oncol, 2015, 16(7): 830-838. DOI: 10.1016/S1470-2045(15)00026-1.

WATANABE S, MINEGISHI Y, YOSHIZAWA H, et al . Effectiveness of gefitinib against non-small-cell lung cancer with the uncommon EGFR mutations G719X and L861Q[J ] . J Thorac Oncol, 2014, 9(2): 189-194. DOI: 10.1097/JTO.0000000000000048.

YANG J C H, SCHULER M, POPAT S, et al . Afatinib for the treatment of NSCLC harboring uncommon EGFR mutations: a database of 693 cases[J ] . J Thorac Oncol, 2020, 15(5): 803-815. DOI: 10.1016/j.jtho.2019.12.126.

KOBAYASHI Y, TOGASHI Y, YATABE Y, et al . EGFR exon 18 mutations in lung cancer: molecular predictors of augmented sensitivity to afatinib or neratinib as compared with first- or third-generation TKIs[J ] . Clin Cancer Res, 2015, 21(23): 5305-5313. DOI: 10.1158/1078-0432.ccr-15-1046.

XU J L, JIN B, CHU T Q, et al . EGFR tyrosine kinase inhibitor (TKI) in patients with advanced non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutations: a real-world study in China[J ] . Lung Cancer, 2016, 96: 87-92. DOI: 10.1016/j.lungcan.2016.01.018.

ZWIERENGA F, VAN VEGGEL B, HENDRIKS L E L, et al . High dose osimertinib in patients with advanced stage E GFR exon 20 mutation-positive NSCLC: results from the phase 2 multicenter POSITION 20 trial[J ] . Lung Cancer, 2022, 170: 133-140. DOI: 10.1016/j.lungcan.2022.06.012.

PARK K, HAURA E B, LEIGHL N B, et al . Amivantamab in EGFR exon 20 insertion-mutated non-small-cell lung cancer progressing on platinum chemotherapy: initial results from the CHRYSALIS phase I study[J ] . J Clin Oncol, 2021, 39(30): 3391-3402. DOI: 10.1200/JCO.21.00662.

JANNE P A, RAMALINGAM S S, YANG J C H, et al . Mobocertinib (TAK-788) in EGFR exon 20 insertion (ex20ins)+ metastatic non-small cell lung cancer (mNSCLC): treatment (tx) beyond progressive disease (PD) in platinum-pretreated patients (pts) with and without intracranial PD[J ] . J Clin Oncol, 2022, 40(16): 9099. DOI: 10.1200/jco.2022.40.16_suppl.9099..

YU H A, TAN D S W, SMIT E F, et al . Phase (Ph) 1/2a study of CLN-081 in patients (pts) with NSCLC with EGFR exon 20 insertion mutations (Ins20)[J ] . J Clin Oncol, 2022, 40(16): 9007. DOI: 10.1200/jco.2022.40.16_suppl.9007.

RIESS J W, KRAILO M D, PADDA S K, et al . Osimertinib plus necitumumab in EGFR-mutant NSCLC: final results from an ETCTN California Cancer Consortium phase I study[J ] . J Clin Oncol, 2022, 40(16): 9014. DOI: 10.1200/jco.2022.40.1 6_suppl.9014.

WANG M, YANG J C H, MITCHELL P, et al . 987P Sunvozertinib for NSCLC patients with EGFR exon 20 insertion mutations: preliminary analysis of WU-KONG6, the first pivotal study[J ] . Ann Oncol, 2022, 33: S1003-S1004. DOI: 10.1016/j.annonc.2022.07.1114.

HOSOMI Y, MORITA S, SUGAWARA S, et al . Gefitinib alone versus gefitinib plus chemotherapy for non-small-cell lung cancer with mutated epidermal growth factor receptor: NEJ009 study[J ] . J Clin Oncol, 2020, 38(2): 115-123. DOI: 10.1200/JCO.19.01488.

NAKAGAWA K, GARON E B, SETO T, et al . 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[J ] . Lancet Oncol, 2019, 20(12): 1655-1669. DOI: 10.1016/S1470-2045(19)30634-5.

NAKAGAWA K, NADAL E, GARON E B, et al . RELAY subgroup analyses by EGFR Ex19del and Ex21 L 858 R mutations for ramucirumab plus erlotinib in metastatic non-small cell lung cancer[J ] . Clin Cancer Res, 2021, 27(19): 5258-5271. DOI: 10.1158/1078-0432.CCR-21-0273..

ZHOU Q, XU C R, CHENG Y, et al . Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): a multicenter phase 3 study[J ] . Cancer Cell, 2021, 39(9): 1279-1291. e3. DOI: 10.1016/j.ccell.2021.07.005.

NAKAMURA A, SAITO R, KO R, et al. A phase Ⅱ study of osimertinib in combination with platinum plus pemetrexed in patients with EGFR-mutated, advanced non-small cell lung cancer: the OPAL study (NEJ032C/LOGIK1801)[J]. J Clin Oncol, 2022, 40: 16_suppl, 9097-9097.

SOO R A, HAN J Y, DAFNI U, et al . A randomised phase Ⅱ study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European thoracic oncology platform (ETOP 10-16) BOOSTER trial[J ] . Ann Oncol, 2022, 33(2): 181-192. DOI: 10.1016/j.annonc.2021.11.010.

KENMOTSU H, WAKUDA K, MORI K, et al . Randomized phase 2 study of osimertinib plus bevacizumab versus osimertinib for untreated patients with nonsquamous NSCLC harboring EGFR mutations: WJOG9717L study[J ] . J Thorac Oncol, 2022, 17(9): 1098-1108. DOI: 10.1016/j.jtho.2022.05.006.

ZHONG W Z, WANG Q, MAO W M, et al . Gefitinib versus vinor elbine plus cisplatin as adjuvant treatment for stage Ⅱ-ⅢA(N1-N 2 )EGFR-mutant NSCLC(ADJUVANT/CTONG 1104): a randomised, open-label, phase 3 study[J ] . Lancet Oncol, 2018, 19(1): 139-148. DOI: 10.1016/S1470-2045(17)30729-5..

ZHONG W Z, WANG Q, MAO W M, et al . Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage Ⅱ-ⅢA (N1-N 2 ) EGFR-mutant NSCLC: final overall sur-vival analysis of CTONG1104 phase Ⅲ trial[J ] . J Clin Oncol, 2021, 39(7): 713-722. DOI: 10.1200/JCO.20.01820..

HE J X, SU C X, LIANG W H, et al . Icotinib versus chemotherapy as adjuvant treatment for stage Ⅱ-ⅢA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial[J ] . Lancet Respir Med, 2021, 9(9): 1021-1029. DOI: 10.1016/S2213-2600(21)00134-X.

WU Y L, TSUBOI M, HE J, et al . Osimertinib in resected EGFR -mutated non-small-cell lung cancer[J ] . N Engl J Med, 2020, 383(18): 1711-1723. DOI: 10.1056/nejmoa2027071..

TSUBOI M, WU Y L, GROHE C, et al . LBA47 Osimertinib as adjuvant therapy in patients (pts) with resected EGFR-mutated (EGFRm) stage IB-ⅢA non-small cell lung cancer (NSCLC): updated results from ADAURA[J ] . Ann Oncol, 2022, 33: S1413-S1414. DOI: 10.1016/j.annonc.2022.08.047.

WOLF J, SETO T, HAN J Y, et al . Capmatinib in MET Exon 14-mutated or MET -amplified non-small-cell lung cancer[J ] . N Engl J Med, 2020, 383(10): 944-957. DOI: 10.1056/nejmoa2002787..

PAIK PK, FELIP E, VEILLON R, et al . Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations[J ] . N Engl J Med. 2020, 383(10): 931-943. DOI: 10.1056/NEJMoa2004407.

KASHIMA K, KAWAUCHI H, TANIMURA H, et al . CH7233163 overcomes osimertinib-resistant EGFR-del19/T790M/C797S mutation[J ] . Mol Cancer Ther, 2020, 19(11): 2288-2297. DOI: 10.1158/1535-7163.MCT-20-0229.

JIA Y, YUN C H, PARK E, et al . Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors[J ] . Nature, 2016, 534(7605): 129-132. DOI: 10.1038/nature17960.

SIENA S, BARTOLOMEO M D, RAGHAV K, et al . Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial[J ] . Lancet Oncol, 2021, 22(6): 779-789. DOI: 10.1016/S1470-2045(21)00086- 3.

BURNETT H, EMICH H, CARROLL C, et al . Epidemiological and clinical burden of EGFR Exon 20 insertion in advanced non-small cell lung cancer: a systematic literature review[J ] . PLoS One, 2021, 16(3): e0247620. DOI: 10.1371/journal.pone.0247620.

ZHOU C C, RAMALINGAM S S, KIM T M, et al . Treatment outcomes and safety of mobocertinib in platinum-pretreated patients with EGFR exon 20 insertion-positive metastatic non-small cell lung cancer[J ] . JAMA Oncol, 2021, 7(12): e214761. DOI: 10.1001/jamaoncol.2021.4761..

NEIJSSEN J, CARDOSO R M F, CHEVALIER K M, et al . Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET[J ] . J Biol Chem, 2021, 296: 100641. DOI: 10.1016/j.jbc.2021.100641.

TSUBOI M, WEDER W, ESCRIU C, et al . Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA[J ] . Future Oncol, 2021, 17(31): 4045-4055. DOI: 10.2217/fon-2021-0549.

SUN L, GUO Y J, SONG J, et al . NeoadjuvantEGFR-TKI therapy for EGFR -mutant NSCLC: a systematic review and pooled analysis of five prospective clinical trials[J ] . Front Oncol, 2021, 10: 586596. DOI: 10.3389/fonc.2020.586596.

UPRETY D, MANDREKAR S J, WIGLE D, et al . Neo-adjuvant immunotherapy for NSCLC: current concepts and future approaches[J ] . J Thorac Oncol, 2020, 15(8): 1281-1297. DOI: 10.1016/j.jtho.2020.05.020.

KANG J, ZHANG C, ZHONG W Z. Neoadjuvant immunotherapy for non-small cell lung cancer: state of the art[J]. Cancer Commun (Lond), 2021, 41(4): 287-302. DOI: 10.1002/cac2.12153.

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