Modern vector in treatment of patients with lung cancer: tyrosine kinase inhibitors in epidermal growth factor receptor mutations (literature review)

O.M. Smorodska; Yu.V. Moskalenko; I.O. Vynnychenko; O.I. Vynnychenko; V.V.  Kostuchenko

doi:10.26641/2307-0404.2021.2.234379

Authors

O.M. Smorodska Sumy State University, Department of oncology and radiology, Rymskogo-Korsakova str., 2, Sumy, 40007, Ukraine, Ukraine https://orcid.org/0000-0002-9028-3379
Yu.V. Moskalenko Sumy State University, Department of oncology and radiology, Rymskogo-Korsakova str., 2, Sumy, 40007, Ukraine, Ukraine https://orcid.org/0000-0002-5398-0298
I.O. Vynnychenko Sumy State University, Department of oncology and radiology, Rymskogo-Korsakova str., 2, Sumy, 40007, Ukraine, Ukraine https://orcid.org/0000-0002-2339-6509
O.I. Vynnychenko Sumy State University, Department of oncology and radiology, Rymskogo-Korsakova str., 2, Sumy, 40007, Ukraine, Ukraine https://orcid.org/0000-0001-5651-0323
V.V. Kostuchenko Sumy State University, Department of oncology and radiology, Rymskogo-Korsakova str., 2, Sumy, 40007, Ukraine, Ukraine https://orcid.org/0000-0001-7301-0945

DOI:

https://doi.org/10.26641/2307-0404.2021.2.234379

Keywords:

afatinib, gefitinib, EGFR, erlotinib, lung cancer, osimertinib

Abstract

Tumor molecular profiling in patients with non-small cell lung cancer (NSCLC) is used to identify driver mutations, which lead to premature carcinogenesis in more than 80% of adenocarcinoma cases, including epidermal growth factor receptor (EGFR) mutations. Identification of specific somatic aberrations allows to personalize treatment. Personalization of treatment resulted in improvement of NSCLC outcomes. The aim of our study was to consider scientific data on modern concepts of treatment of patients with non-small cell lung cancer with previously detected oncogenic mutations, especially EGFR mutation. In our study we analyzed scientific papers and data of international scientific literature on the problem of lung cancer treatment. Methods used: scientific research, analytical and generalizing. Different drugs are used in treatment of lung cancer. Choice of treatment scheme depends on type and presence of mutations. Patients with advanced non-small-cell lung cancer and detected mutation in the EGFR can be treated with tyrosine kinase inhibitors (TKIs). Nowadays three first generation drugs are recommended by FDA: afatinib, erlotinib, gefitinib. They showed good clinical benefit. Most patients with metastatic NSCLC typically show disease progression after approximately 9 to 13 months of erlotinib, gefitinib, or afatinib therapy. The first and only commercially available third-generation EGFR TKI is оsimertinib - an oral drug, which selectively inhibits both EGFR-TKI and EGFR T790M resistance mutations. Nowadays scientists are in active investigation of mechanisms of acquired resistance to TKIs, but little is known yet. Clinical success can be observed in patients who were treated with TKIs. EGFR T790M is a mutation that leads to acquired resistance to EGFR TKI therapy. Its incidence is approximately 60% after disease progression on TKI drugs (erlotinib, gefitinib, or aphatinib). Third-generation EGFR TKIs demonstrate high efficacy, but acquired resistance development cannot be avoided. Mechanisms of acquired resistance to these agents are still investigated.

References

Zhang Y, Chen Z, Zhang X, Xu C, Yan H, Xie Z, et al. Analysis of resistance mechanisms to abivertinib, a third-generation EGFR tyrosine kinase inhibitor, in patients with EGFR T790M-positive non-small cell lung cancer from a phase I trial. EBioMedicine. 2019;43:180-7. doi: https://doi.org/10.1016/j.ebiom.2019.04.030

Goto K, Nishio M, Yamamoto N, Chikamori K, Hida T, Maemondo M, et al. A prospective, phase II, open-label study (JO22903) of first-line erlotinib in Japanese patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC). Lung Cancer. 2013;82:109-14. doi: https://doi.org/10.1016/j.lungcan.2013.07.003

Chen R, Chen H, Jiang B, Zhang X, Zhou Q, Tu H, et al. Bevacizumab plus chemotherapy for patients with advanced pulmonary adenocarcinoma harboring EGFR mutations. Clinical and Translational Oncology. 2017;20(2):243-52.

doi: https://doi.org/10.1007/s12094-017-1714-2

Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, 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. Lancet Oncol. 2015;16(7):830-8. doi: https://doi.org/10.1016/S1470-2045(15)00026-1

Lou N, Zhang X, Chen H, Zhou Q, Yan L, Xie Z, et al. Clinical outcomes of advanced non-small-cell lung cancer patients with EGFR mutatio, ALK rearrangement and EGFR/ALK co-alterations. Oncotarget. 2016;7(40):65185-95. doi: https://doi.org/10.18632/oncotarget.11218

Da Cunha Santos G, Shepherd FA, Tsao MS. EGFR mutations and lung cancer. Annu Rev Pathol. 2011;6:49-69.

doi: https://doi.org/10.1146/annurev-pathol-011110-130206

Dearden S, Stevens J, Wu YL and Blowers D. Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap). Ann Oncol. 2013;24:2371-6. doi: https://doi.org/10.1093/annonc/mdt205

Finlay MR, Anderton M, Ashton S, Ballard P, Bethel PA, Box MR, et al. Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor. J Med Chem. 2014;57:8249-67. doi: https://doi.org/10.1021/jm500973a

Tetsu O, Hangauer M, Phuchareon J, Eisele D, McCormick F. Drug Resistance to EGFR Inhibitors in Lung Cancer. Chemotherapy. 2016;61(5):223-35. doi: https://doi.org/10.1159/000443368

Dungo RT, Keating GM. Afatinib: first global approval. Drugs. 2013;73:1503-15. doi: https://doi.org/10.1007/s40265-013-0111-6

Yi L, Fan J, Qian R, Luo P, Zhang J. Efficacy and safety of osimertinib in treating EGFR‐mutated advanced NSCLC: A meta‐analysis. International Journal of Cancer. 2019;145(1):284-94. doi: https://doi.org/10.1002/ijc.32097

Arcila ME, Nafa K, Chaft JE, Rekhtman N, Lau C, Reva BA, et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013;12:220-9.

doi: https://doi.org/10.1158/1535-7163.MCT-12-0620

Konduri K, Gallant J, Chae Y, Giles F, Gitlitz B, Gowen K, et al. EGFR Fusions as Novel Therapeutic Targets in Lung Cancer. Cancer Discovery. 2016;6(6):601-11.

doi: https://doi.org/10.1158/2159-8290.CD-16-0075

Ripamonti F, Albano L, Rossini A, et al. EGFR through STAT3 modulates ΔN63α expression to sustain tumor-initiating cell proliferation in squamous cell carcinomas. J Cell Physiol. 2013;228:871-8. doi: https://doi.org/10.1002/jcp.24238

Antonicelli A, Cafarotti S, Indini A, Galli A, Russo A, Cesario A et al. EGFR-targeted therapy for non-small cell lung cancer: focus on EGFR oncogenic mutation. Int J Med Sci. 2013;10:320-30. doi: https://doi.org/10.7150/ijms.4609

Shepherd FA, Pereira JR, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353(2):123-32. doi: https://doi.org/10.1056/NEJMoa050753

Jiang Y, Zhang J, Huang J, Xu B, Li N, Cao L, et al. Erlotinib versus gefitinib for brain metastases in Asian patients with exon 19 EGFR-mutant lung adenocar¬cinoma: a retrospective, multicenter study. BMC Pulmonary Medicine. 2018;18(1). doi: https://doi.org/10.1186/s12890-018-0734-1

Yu X, Zhang X, Zhang Z, Lin Y, Wen Y, Chen Y, et al. First-generation EGFR tyrosine kinase inhi¬bitor therapy in 106 patients with compound EGFR-mutated lung cancer: a single institution's clinical practice experience. Cancer Communications. 2018;38(1):51. doi: https://doi.org/10.1186/s40880-018-0321-0

Giaccone G, Herbst RS, Manegold C, Scag¬liotti G, Rosell R, Natale VMRB, et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial ‒ INTACT 1. J Clin Oncol. 2004;22(5):777-84. doi: https://doi.org/10.1200/JCO.2004.08.001

Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947-57. doi: https://doi.org/10.1056/NEJMoa0810699

Chang C, Lee C, Ko J, Chang L, Lee M, Wang J, et al. Gefitinib or erlotinib in previously treated non-small-cell lung cancer patients: a cohort study in Taiwan. Cancer Medicine. 2017;6(7):1563-72. doi: https://doi.org/10.1002/cam4.1121

Chang I, Jiang S, Yang J, Su W, Chien L, Hsiao C, et al. Genetic Modifiers of Progression-Free Survival in Never-Smoking Lung Adenocarcinoma Pa¬tients Treated with First-Line Tyrosine Kinase Inhibitors. American Journal of Respiratory and Critical Care Medicine.2017;195(5):663-73. doi: https://doi.org/10.1164/rccm.201602-0300OC

Im J, Herrmann A, Bernatchez C, Haymaker C, Molldrem J, Hong W, et al. Immune-Modulation by Epidermal Growth Factor Receptor Inhibitors: Implica¬tion on Anti-Tumor Immunity in Lung Cancer. PLOS ONE. 2016;11(7):e0160004. doi: https://doi.org/10.1371/journal.pone.0160004

Santoni-Rugiu E, Melchior L, Urbanska E, Jakobsen J, Stricker K, Grauslund M, et al. Intrinsic resistance to EGFR-Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer: Differences and Similarities with Acquired Resistance. Cancers. 2019;11(7):923. doi: https://doi.org/10.3390/cancers11070923

Ke E, Wu Y. Afatinib in the first-line treatment of epidermal-growth-factor-receptor mutation-positive non-small cell lung cancer: a review of the clinical evidence. Therapeutic Advances in Respiratory Disease. 2016;10(3):256-64. doi: https://doi.org/10.1177/1753465816634545

Kennedy BJ. The snail’s pace of lung carcinoma chemotherapy cancer. Cancer. 1998;82(5):801-3. doi: https://doi.org/10.1002/(SICI)1097-0142(19980301)82:5<801::AID-CNCR1>3.0.CO;2-M

Liu X, Wang P, Zhang C, Ma Z. Epidermal growth factor receptor (EGFR): A rising star in the era of precision medicine of lung cancer. Oncotarget. 2017;8(30):50209-20. doi: https://doi.org/10.18632/oncotarget.16854

Westover D, Zugazagoitia J, Cho B, Lovly C, Paz-Ares L. Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors. Annals of Oncology. 2018;29:10-19. doi: https://doi.org/10.1093/annonc/mdx703

Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res. 2015;5(9):2892-911. PMID: 26609494; PMCID: PMC4633915.

Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Nishiwaki JYDY, et al. Multi-institutional ran¬domized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol. 2003;21(12):2237-46. doi: https://doi.org/10.1200/JCO.2003.10.038

Ettinger DS, Wood D E, Aisner D L, Akerley W, Bauman J, Chirieac LR, et al. Non-Small Cell Lung Cancer, Version 5.2017. Clinical Practice Guidelines in Oncology.JNCCN.2017;15(4):504-534. doi: https://doi.org/10.6004/jnccn.2017.0050

Zhou W, Ercan D, Chen I, Yun CH, Li D, Chapelletti M, et al. Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature. 2000;462(7276):1070-4. doi: https://doi.org/10.1038/nature08622

Wen F, Zheng H, Zhang P, Hutton D, Li Q. OPTIMAL and ENSURE trials-based combined cost-effectiveness analysis of erlotinib versus chemotherapy for the first-line treatment of Asian patients with non-squamous non-small-cell lung cancer. BMJ Open. 2018;8(4):e020128.

doi: https://doi.org/10.1136/bmjopen-2017-020128

Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376:629-40. doi: https://doi.org/10.1056/NEJMoa1612674

Pakkala S, Ramalingam S. Personalized therapy for lung cancer: Striking a moving target. JCI Insight. 2018;3(15):120858. doi: https://doi.org/10.1172/jci.insight.120858

Bonomi P, Gandara D, Hirsch F, Kerr K, Obasaju C, Paz-Ares L, et al. Predictive biomarkers for res¬ponse to EGFR-directed monoclonal antibodies for ad¬vanced squamous cell lung cancer. Annals of Oncology. 2018;29(8):1701-9. doi: https://doi.org/10.1093/annonc/mdy196

Riely GJ, Kris MG, Zhao B, Tim A, Milton DT, Moore E, et al. Prospective assessment of discontinuation and reinitiation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of everolimus. Clin Cancer Res. 2007;13:5150-5.

doi: https://doi.org/10.1158/1078-0432.CCR-07-0560

Leonetti A, Sharma S, Minari R, Perego P, Giovannetti E, Tiseo M. Resistance mechanisms to osimer¬tinib in EGFR-mutated non-small cell lung cancer. British Journal of Cancer. 2019;121(9):725-37. doi: https://doi.org/10.1038/s41416-019-0573-8

Paik PK, Varghese AM, Sima CS, Moreira AL, Ladanyi M, Kris MG, et al. Response to erlotinib in patients with EGFR mutant advanced non-small cell lung cancers with a squamous or squamous-like component. Mol Cancer Ther. 2012;11:2535-40. doi: https://doi.org/10.1158/1535-7163.MCT-12-0163

Ricciuti B, Baglivo S, De Giglio A, Chiari R. Afatinib in the first-line treatment of patients with non-small cell lung cancer: clinical evidence and experience. Therapeutic Advances in Respiratory Disease. 2018;12:175346661880865. doi: https://doi.org/10.1177/1753466618808659

Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007;7:169-81. doi: https://doi.org/10.1038/nrc2088

Siegel R, Naishadham D, Jemal A. Cancer statistics 2013. CA Cancer J Clin 2013;63:11-30. doi: https://doi.org/10.3322/caac.21166

Soria J.-C, Ohe Y, Vansteenkiste J, Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer N Engl J Med. 2018;378(2):113-25. doi: https://doi.org/10.1056/NEJMoa1713137

Stewart EL, Tan SZ, Liu G. Known and putative mechanism of resistance to EGFR targeted therapies in NSCLC patients with EGFR mutations-a review. Transl Lung Cancer Res. 2015;4(1):67-81. doi: https://doi.org/10.3978/j.issn.2218-6751.2014.11.06

Masters GA, Temin S, Azzoli CG, Giaccone G, Baker S, Brahmer JR, et al. Systemic therapy for Stage IV non small cell lung cancer: American Society of Clinical Oncology Clinical Practice Guideline update. J Clin Oncol. 2015;33:3488-515. doi: https://doi.org/10.1200/JCO.2015.62.1342

Gou L, Li A, Yang J, Zhang X, Su J, Yan H, et al. The coexistence of MET over-expression and an EGFR T790M mutation is related to acquired resistance to EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer. Oncotarget. 2016;7(32):51311-9. doi: https://doi.org/10.18632/oncotarget.9697

Tseng J, Su K, Yang T, Chen K, Hsu K, Chen H, et al. The emergence of T790M mutation in EGFR-mutant lung adenocarcinoma patients having a history of acquired resistance to EGFR-TKI: focus on rebiopsy timing and long-term existence of T790M. Oncotarget. 2016;7(30):48059-69. doi: https://doi.org/10.18632/oncotarget.10351

Ochiai S, Nomoto Y, Watanabe Y, Yamashita Y, Toyomasu Y, Kawamura T, et al. The impact of epider¬mal growth factor receptor mutations on patterns of disease recurrence after chemoradiotherapy for locally advanced non–small cell lung cancer: a literature review and pooled analysis. Journal of Radiation Research. 2016;57(5):449-59. doi: https://doi.org/10.1093/jrr/rrw075

Wu S, Shih J. Management of acquired resistance to EGFR TKI–targeted therapy in advanced non-small cell lung cancer. Molecular Cancer. 2018;17(1). doi: https://doi.org/10.1186/s12943-018-0777-1

Zhang C, Leighl N, Wu Y, Zhong W. Emerging therapies for non-small cell lung cancer. Jour¬nal of Hematology & Oncology. 2019;12(1). doi: https://doi.org/10.1186/s13045-019-0731-8