nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

28.06.2020 | Review – Clinical Oncology

Non-small cell lung cancer patients with ex19del or exon 21 L858R mutation: distinct mechanisms, different efficacies to treatments

verfasst von: W.-Q. Li, J.-W. Cui

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 9/2020

Einloggen, um Zugang zu erhalten

Abstract

With the development of antitumor therapies, different treatment methods including monotherapy and combined therapy have achieved clinical efficacy in advanced epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients. Exon 19 deletion (ex19del) and exon 21 L858R mutation are common sensitive subtypes of EGFR mutation. However, potential distinct mechanisms are found from several dimensions including molecular structures, biological behaviors, concomitant mutations, resistance mechanisms and tumor mutation burdens. More evidence indicates the prognostic difference of EGFR subgroups. This review focused on the progress of potential distinct mechanisms and outcomes in clinical trials of advanced NSCLC patients with ex19del or exon 21 L858R mutation.

Barnet MB, O'Toole S, Horvath LG, Selinger C, Yu B, Ng CC et al (2017) EGFR-Co-mutated advanced NSCLC and response to EGFR tyrosine kinase inhibitors. J Thorac Oncol 12(3):585–590PubMed

Castellanos E, Feld E, Horn L (2017) Driven by mutations: the predictive value of mutation subtype in EGFR-mutated non-small cell lung cancer. J Thorac Oncol 12(4):612–623PubMed

Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH et al (2016) Randomized phase II trial of gefitinib with and without pemetrexed as first-line therapy in patients with advanced nonsquamous non-small-cell lung cancer with activating epidermal growth factor receptor mutations. J Clin Oncol 34(27):3258–3266PubMed

Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ et al (2014) AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov 4(9):1046–1061PubMedPubMedCentral

Fukuoka M, Wu YL, Thongprasert S, Sunpaweravong P, Leong SS, Sriuranpong V et al (2011) Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol 29(21):2866–2874PubMed

Goag EK, Lee JM, Chung KS, Kim SY, Leem AY, Song JH et al (2018) Usefulness of bronchoscopic rebiopsy of non-small cell lung cancer with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor. J Cancer 9(6):1113–1120PubMedPubMedCentral

Gunther M, Juchum M, Kelter G, Fiebig H, Laufer S (2016) Lung cancer: EGFR inhibitors with low nanomolar activity against a therapy-resistant L858R/T790M/C797S mutant. Angew Chem Int Ed Engl 55(36):10890–10894PubMed

Han B, Jin B, Chu T, Niu Y, Dong Y, Xu J et al (2017) Combination of chemotherapy and gefitinib as first-line treatment for patients with advanced lung adenocarcinoma and sensitive EGFR mutations: a randomized controlled trial. Int J Cancer 141(6):1249–1256PubMed

Harrison PT, Vyse S, Huang PH (2020) Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer. Semin Cancer Biol 61:167–179PubMedPubMedCentral

Hastings K, Yu HA, Wei W, Sanchez-Vega F, DeVeaux M, Choi J et al (2019) EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer. Ann Oncol 30(8):1311–1320PubMedPubMedCentral

Ho GF, Chai CS, Alip A, Wahid MIA, Abdullah MM, Foo YC et al (2019) Real-world experience of first-line afatinib in patients with EGFR-mutant advanced NSCLC: a multicenter observational study. BMC Cancer 19(1):896PubMedPubMedCentral

Hochmair MJ, Morabito A, Hao D, Yang CT, Soo RA, Yang JC et al (2018) Sequential treatment with afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: an observational study. Future Oncol 14(27):2861–2874PubMed

Hochmair MJ, Morabito A, Hao D, Yang CT, Soo RA, Yang JC et al (2019) Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: updated analysis of the observational GioTag study. Future Oncol 15(25):2905–2914PubMed

Hong S, Gao F, Fu S, Wang Y, Fang W, Huang Y et al (2018) Concomitant genetic alterations with response to treatment and epidermal growth factor receptor tyrosine kinase inhibitors in patients with EGFR-mutant advanced non-small cell lung cancer. JAMA Oncol 4(5):739–742PubMedPubMedCentral

Hong W, Wu Q, Zhang J, Zhou Y (2019) Prognostic value of EGFR 19-del and 21–L858R mutations in patients with non-small cell lung cancer. Oncol Lett 18(4):3887–3895PubMedPubMedCentral

Hosomi Y, Morita S, Sugawara S, Kato T, Fukuhara T, Gemma A et al (2020) Gefitinib alone versus gefitinib plus chemotherapy for non-small-cell lung cancer with mutated epidermal growth factor receptor: NEJ009 study. J Clin Oncol 38(2):115–123PubMed

Jiao XD, He X, Qin BD, Liu K, Wu Y, Liu J et al (2019) The prognostic value of tumor mutation burden in EGFR-mutant advanced lung adenocarcinoma, an analysis based on cBioPortal data base. J Thorac Dis 11(11):4507–4515PubMedPubMedCentral

Karachaliou N, Mayo-de las Casas C, Queralt C, de Aguirre I, Melloni B, Cardenal F et al (2015) Association of EGFR L858R mutation in circulating free DNA with survival in the EURTAC trial. JAMA Oncol 1(2):149–157PubMed

Ke EE, Zhou Q, Zhang QY, Su J, Chen ZH, Zhang XC et al (2017) A higher proportion of the EGFR T790M mutation may contribute to the better survival of patients with exon 19 deletions compared with those with L858R. J Thorac Oncol 12(9):1368–1375PubMed

Kuan FC, Kuo LT, Chen MC, Yang CT, Shi CS, Teng D et al (2015) Overall survival benefits of first-line EGFR tyrosine kinase inhibitors in EGFR-mutated non-small-cell lung cancers: a systematic review and meta-analysis. Br J Cancer 113(10):1519–1528PubMedPubMedCentral

Kumar A, Petri ET, Halmos B, Boggon TJ (2008) Structure and clinical relevance of the epidermal growth factor receptor in human cancer. J Clin Oncol 26(10):1742–1751PubMed

Lau SC, Chooback N, Ho C, Melosky B (2019) Outcome differences between first- and second-generation EGFR inhibitors in advanced EGFR mutated NSCLC in a Large population-based cohort. Clin Lung Cancer 20(5):e576–e583PubMed

Lee DH (2017) Treatments for EGFR-mutant non-small cell lung cancer (NSCLC): the road to a success, paved with failures. Pharmacol Ther 174:1–21PubMed

Li Y, Appius A, Pattipaka T, Feyereislova A, Cassidy A, Ganti AK (2019) Real-world management of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer in the USA. PLoS ONE 14(1):e0209709PubMedPubMedCentral

Li X, Zhang L, Jiang D, Wang Y, Zang A, Ding C et al (2020) Routinedose and high-dose Icotinib in advanced non-small cell lung cancer patients harboring EGFR Exon 21 L858R mutation: the randomized, Phase II, INCREASE Trial. Clin Cancer Res. https://doi.org/10.1158/1078-0432.CCR-19-3064 CrossRefPubMedPubMedCentral

London M, Gallo E (2020) Epidermal growth factor receptor (EGFR) involvement in epithelial-derived cancers and its current antibody-based immunotherapies. Cell Biol Int 44:1267–1282PubMed

Marquez-Medina D, Popat S (2016) Eventual role of EGFR-tyrosine kinase inhibitors in early-stage non-small-cell lung cancer. Future Oncol 12(6):815–825PubMed

Massarelli E, Johnson FM, Erickson HS, Wistuba II, Papadimitrakopoulou V (2013) Uncommon epidermal growth factor receptor mutations in non-small cell lung cancer and their mechanisms of EGFR tyrosine kinase inhibitors sensitivity and resistance. Lung Cancer 80(3):235–241PubMed

Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N et al (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361(10):947–957PubMed

Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S et al (2018) 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 Clin Oncol 36(22):2244–2250PubMed

Nagano T, Tachihara M, Nishimura Y (2018) Mechanism of resistance to epidermal growth factor receptor-tyrosine kinase inhibitors and a potential treatment strategy. Cells 7(11):212PubMedCentral

Nakagawa K, Garon EB, Seto T, Nishio M, Ponce Aix S, Paz-Ares L et al (2019) 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 20(12):1655–1669PubMed

Offin M, Rizvi H, Tenet M, Ni A, Sanchez-Vega F, Li BT et al (2019) Tumor mutation burden and efficacy of EGFR-tyrosine kinase inhibitors in patients with egfr-mutant lung cancers. Clin Cancer Res 25(3):1063–1069PubMed

Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304(5676):1497–1500PubMed

Papadimitrakopoulou VA, Han JY, Ahn MJ, Ramalingam SS, Delmonte A, Hsia TC et al (2020) Epidermal growth factor receptor mutation analysis in tissue and plasma from the AURA3 trial: osimertinib versus platinum-pemetrexed for T790M mutation-positive advanced non-small cell lung cancer. Cancer 126(2):373–380PubMed

Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T et al (2016) Afatinib 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. Lancet Oncol 17(5):577–589PubMed

Paz-Ares L, Tan EH, O'Byrne K, Zhang L, Hirsh V, Boyer M et al (2017) 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. Ann Oncol 28(2):270–277PubMedPubMedCentral

Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y et al (2020) Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med 382(1):41–50PubMed

Reguart N, Remon J (2015) Common EGFR-mutated subgroups (Del19/L858R) in advanced non-small-cell lung cancer: chasing better outcomes with tyrosine kinase inhibitors. Future Oncol 11(8):1245–1257PubMed

Riely GJ, Pao W, Pham D, Li AR, Rizvi N, Venkatraman ES et al (2006) Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib. Clin Cancer Res 12(3 Pt 1):839–844PubMed

Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E et al (2012) Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 13(3):239–246PubMed

Roskoski R Jr (2019) Small molecule inhibitors targeting the EGFR/ErbB family of protein-tyrosine kinases in human cancers. Pharmacol Res 139:395–411PubMed

Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S et al (2019) 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 20(5):625–635PubMed

Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T et al (2013) Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 31(27):3327–3334PubMed

Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y et al (2014) Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol 15(11):1236–1244PubMed

Shi YK, Wang L, Han BH, Li W, Yu P, Liu YP et al (2017) 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. Ann Oncol 28(10):2443–2450PubMed

Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69(1):7–34PubMed

Sordella R, Bell DW, Haber DA, Settleman J (2004) Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 305(5687):1163–1167PubMed

Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH et al (2018) Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 378(2):113–125PubMed

Sutiman N, Tan SW, Tan EH, Lim WT, Kanesvaran R, Ng QS et al (2017) EGFR mutation subtypes influence survival outcomes following first-line gefitinib therapy in advanced asian NSCLC patients. J Thorac Oncol 12(3):529–538PubMed

Thress KS, Paweletz CP, Felip E, Cho BC, Stetson D, Dougherty B et al (2015) Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med 21(6):560–562PubMedPubMedCentral

Tsai MF, Chang TH, Wu SG, Yang HY, Hsu YC, Yang PC et al (2015) EGFR-L858R mutant enhances lung adenocarcinoma cell invasive ability and promotes malignant pleural effusion formation through activation of the CXCL12-CXCR4 pathway. Sci Rep 5:13574PubMedPubMedCentral

Wang S, Li J (2019) Second-generation EGFR and ErbB tyrosine kinase inhibitors as first-line treatments for non-small cell lung cancer. Onco Targets Ther 12:6535–6548PubMedPubMedCentral

Wang S, Tsui ST, Liu C, Song Y, Liu D (2016) EGFR C797S mutation mediates resistance to third-generation inhibitors in T790M-positive non-small cell lung cancer. J Hematol Oncol 9(1):59PubMedPubMedCentral

Wang ZF, Ren SX, Li W, Gao GH (2018) Frequency of the acquired resistant mutation T790 M in non-small cell lung cancer patients with active exon 19Del and exon 21 L858R: a systematic review and meta-analysis. BMC Cancer 18(1):148PubMedPubMedCentral

Wee P, Wang Z (2017) Epidermal growth factor receptor cell proliferation signaling pathways. Cancers (Basel) 9(5):52

Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y et al (2014) Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 15(2):213–222PubMed

Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S et al (2017) 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. Lancet Oncol 18(11):1454–1466PubMed

Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N et al (2015) Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 16(2):141–151PubMed

Yun CH, Boggon TJ, Li Y, Woo MS, Greulich H, Meyerson M et al (2007) Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell 11(3):217–227PubMedPubMedCentral

Zaric B, Stojsic V, Kovacevic T, Sarcev T, Tepavac A, Jankovic R et al (2014) Clinical characteristics, tumor, node, metastasis status, and mutation rate in domain of epidermal growth factor receptor gene in serbian patients with lung adenocarcinoma. J Thorac Oncol 9(9):1406–1410PubMed

Zeng L, Xiao L, Jiang W, Yang H, Hu D, Xia C et al (2020) Investigation of efficacy and acquired resistance for EGFR-TKI plus bevacizumab as first-line treatment in patients with EGFR sensitive mutant non-small cell lung cancer in a Real world population. Lung Cancer 141:82–88PubMed

Zhang Y, Sheng J, Kang S, Fang W, Yan Y, Hu Z et al (2014) Patients with exon 19 deletion were associated with longer progression-free survival compared to those with L858R mutation after first-line EGFR-TKIs for advanced non-small cell lung cancer: a meta-analysis. PLoS ONE 9(9):e107161PubMedPubMedCentral

Zhang Y, Ma Y, Li Y, Shen X, Yu Y, Pan Y et al (2018) Are exon 19 deletions and L858R different in early stage lung adenocarcinoma? J Cancer Res Clin Oncol 144(1):165–171PubMed

Zhao Y, Liu J, Cai X, Pan Z, Liu J, Yin W et al (2019) Efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor mutated, non-small cell lung cancer: systematic review and network meta-analysis. BMJ 367:l5460PubMedPubMedCentral

Zhou Q, Wu YL, Cheng Y, Liu Y, Chen G, Cui J et al (2019) CTONG 1509: Phase III study of bevacizumab with or without erlotinib in untreated Chinese patients with advanced EGFR-mutated NSCLC. Ann Oncol 30:603

Zhu JQ, Zhong WZ, Zhang GC, Li R, Zhang XC, Guo AL et al (2008) Better survival with EGFR exon 19 than exon 21 mutations in gefitinib-treated non-small cell lung cancer patients is due to differential inhibition of downstream signals. Cancer Lett 265(2):307–317PubMed

Titel: Non-small cell lung cancer patients with ex19del or exon 21 L858R mutation: distinct mechanisms, different efficacies to treatments
verfasst von: W.-Q. Li
J.-W. Cui
Publikationsdatum: 28.06.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 9/2020
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-020-03296-6

Neu im Fachgebiet Onkologie

23.04.2024 | Medikamente in Schwangerschaft und Stillzeit | Nachrichten

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Non-small cell lung cancer patients with ex19del or exon 21 L858R mutation: distinct mechanisms, different efficacies to treatments

Abstract

Neu im Fachgebiet Onkologie

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Stufenschema weist Prostatakarzinom zuverlässig nach

Update Onkologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 9/2020

PROLAPSE: survey about local prostate cancer relapse salvage treatment with external beam re-irradiation: results of the Italian Association of Radiotherapy and Clinical Oncology (AIRO)

Targeting glycolysis with 2-deoxy-d-glucose sensitizes primary cell cultures of renal cell carcinoma to tyrosine kinase inhibitors

Lymphocyte activation gene-3 (LAG3) mRNA and protein expression on tumour infiltrating lymphocytes (TILs) in oesophageal adenocarcinoma

Volumetric modulated arc therapy versus intensity-modulated proton therapy in the postoperative irradiation of thymoma

Bone marrow adipocytes enhance osteolytic bone destruction by activating 1q21.3(S100A7/8/9-IL6R)-TLR4 pathway in lung cancer

Microarray analysis of the expression profile of immune-related gene in rapid recurrence early-stage lung adenocarcinoma

Neu im Fachgebiet Onkologie

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Stufenschema weist Prostatakarzinom zuverlässig nach

Update Onkologie