A Review of EGFR-Mutant Non‑Small Cell Lung Cancer (NSCLC) in 2024
Abstract
Twenty years ago, our understanding of non-small cell lung cancer (NSCLC) treatment was revolutionized by the demonstration of a strong relationship between activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) and the response to tyrosine kinase inhibitors such as gefitinib. These experiments, among many others, have paved the way for two decades of exponential therapeutic growth that we have witnessed.
EGFR-mutant lung cancers account for as much as 23% of NSCLC cases diagnosed in Canada, with significant variations based on geography and ethnicity including a higher prevalence in regions where the Asian population is more important. Therefore, the latest data discussed in this article have the potential to improve outcomes for a large number of patients.
References
Sara Kuruvilla M, Liu G, Syed I, Gwadry-Sridhar F, Sheffield BS, Sachdeva R, et al. EGFR mutation prevalence, real-world treatment patterns, and outcomes among patients with resected, early-stage, non-small cell lung cancer in Canada. Lung Cancer. 2022;173:58-66. doi:10.1016/j.lungcan.2022.08.023
Wu YL, Tsuboi M, He J, John T, Grohe C, Majem M, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723. doi:10.1056/NEJMoa2027071
Herbst RS, Wu YL, John T, Grohe C, Majem M, Wang J, et al. Adjuvant osimertinib for resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer: updated results from the phase III randomized ADAURA trial. J Clin Oncol. 2023;41(10):1830-1840. doi:10.1200/jco.22.02186
Tsuboi M, Herbst RS, John T, Kato T, Majem M, Grohé C, et al. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389(2):137-147. doi:10.1056/NEJMoa2304594
Yan D. Hope and challenges: immunotherapy in EGFR-mutant NSCLC patients. Biomedicines. 2023;11(11). doi:10.3390/biomedicines11112916
Heymach JV, Harpole D, Mitsudomi T, Taube JM, Galffy G, Hochmair M, et al. Perioperative durvalumab for resectable non-small-cell lung cancer. N Engl J Med. 2023;389(18):1672-1684. doi:10.1056/NEJMoa2304875
Schoenfeld AJ, Arbour KC, Rizvi H, Iqbal AN, Gadgeel SM, Girshman J, et al. Severe immune-related adverse events are common with sequential PD-(L)1 blockade and osimertinib. Ann Oncol. 2019;30(5):839-844. doi:10.1093/annonc/mdz077
Tsuboi M, Weder W, Escriu C, Blakely C, He J, Dacic S, et al. Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA. Future Oncol. 2021;17(31):4045-4055. doi:10.2217/fon-2021-0549
Lu S, Casarini I, Kato T, Cobo M, Özgüroğlu M, Hodge R, et al. Osimertinib maintenance after definitive chemoradiation in patients with unresectable EGFR mutation positive stage III non-small-cell lung cancer: LAURA trial in progress. Clin Lung Cancer. 2021;22(4):371-375. doi:10.1016/j.cllc.2020.11.004
Jung HA, Ku BM, Kim YJ, Park S, Sun JM, Lee SH, et al. Longitudinal monitoring of circulating tumor DNA from plasma in patients with curative resected stages I to IIIA EGFR-mutant non-small cell lung cancer. J Thorac Oncol. 2023;18(9):1199-1208. doi:10.1016/j.jtho.2023.05.027
Franzi S, Seresini G, Borella P, Raviele PR, Bonitta G, Croci GA, et al. Liquid biopsy in non-small cell lung cancer: a meta-analysis of state-of-the-art and future perspectives. Front Genet. 2023;14:1254839. doi:10.3389/fgene.2023.1254839
Lamb YN. Osimertinib: a review in previously untreated, EGFR mutation-positive, advanced NSCLC. Target Oncol. 2021;16(5):687-695. doi:10.1007/s11523-021-00839-w
Harrison PT, Vyse S, Huang PH. Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer. Semin Cancer Biol. 2020;61:167-179. doi:10.1016/j.semcancer.2019.09.015
Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020;382(1):41-50. doi:10.1056/NEJMoa1913662
Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125. doi:10.1056/NEJMoa1713137
Li WY, Zhao TT, Xu HM, Wang ZN, Xu YY, Han Y, et al. The role of EGFR mutation as a prognostic factor in survival after diagnosis of brain metastasis in non-small cell lung cancer: a systematic review and meta-analysis. BMC Cancer. 2019;19(1):145. doi:10.1186/s12885-019-5331-z
Kelly WJ, Shah NJ, Subramaniam DS. Management of brain metastases in epidermal growth factor receptor mutant non-small-cell lung cancer. Front Oncol. 2018;8:208. doi:10.3389/fonc.2018.00208
Planchard D, Jänne PA, Cheng Y, Yang JC, Yanagitani N, Kim SW, et al. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948. doi:10.1056/NEJMoa2306434
Cho BC, Felip E, Spira AI, Girard N, Lee J, Lee S, et al. Amivantamab plus lazertinib vs osimertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): primary results from MARIPOSA, a phase III, global, randomized, controlled trial. Annals of Oncology. 2023;34:S1254-S1335. doi:10.1016/annonc/annonc1358
Yang JC-H, Lee DH, Lee J-S, Fan Y, Marinis Fd, Okamoto I, et al. Pemetrexed and platinum with or without pembrolizumab for tyrosine kinase inhibitor (TKI)-resistant, EGFR-mutant, metastatic nonsquamous NSCLC: phase 3 KEYNOTE-789 study. Journal of Clinical Oncology. 2023;41(17_suppl):LBA9000-LBA9000. doi:10.1200/JCO.2023.41.17_suppl.LBA9000
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):830-838. doi:10.1016/s1470-2045(15)00026-1
Miura S, Tanaka H, Misumi T, Yoshioka H, Kurata T, Tokiko T, et al. Afatinib versus chemotherapy for treatment-naïve non-small cell lung cancer with a sensitizing uncommon epidermal growth factor receptor mutation: a phase III study (ACHILLES/TORG1834). Annals of Oncology. 2023;32:S1310-S1311. doi:https://doi.org/10.1016/j.annonc.2023.10.067
Bar J, Peled N, Schokrpur S, Wolner M, Rotem O, Girard N, et al. UNcommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-Life Practice in First-LiNe Setting (UNICORN). J Thorac Oncol. 2023;18(2):169-180. doi:10.1016/j.jtho.2022.10.004
Cho JH, Lim SH, An HJ, Kim HH, Park KU, Kang EJ, et al. Final overall survival analysis of osimertinib for patients with NSCLC harboring uncommon EGFR mutations (KCSG-LU15-09). Journal of Thoracic Surgery. 2023;18(11). doi:https://doi.org/10.1016/j.jtho.2023.09.206
Leonetti A, Sharma S, Minari R, Perego P, Giovannetti E, Tiseo M. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. Br J Cancer. 2019;121(9):725-737. doi:10.1038/s41416-019-0573-8
Coleman N, Hong L, Zhang J, Heymach J, Hong D, Le X. Beyond epidermal growth factor receptor: MET amplification as a general resistance driver to targeted therapy in oncogene-driven non-small-cell lung cancer. ESMO Open. 2021;6(6):100319. doi:10.1016/j.esmoop.2021.100319
Kim TM, Guarneri V, Jye VP, Yang J-J, Wislez M, Huang C, et al. Tepotinib + osimertinib in EGFR-mutant NSCLC with MET amplification following 1L osimertinib: INSIGHT 2 primary analysis. Journal of Thoracic Oncology. 2023;18(11):S94. doi:https://doi.org/10.1016/j.jtho.2023.09.106.
Rotow J, Patel J, Hanley M, Yu H, Goldman H, Nechustan H, et al. Combination osimertinib plus selpercatinib for EGFR-mutant non-small cell lung cancer (NSCLC) with acquired RET fusions. Journal of Thoracic Oncology. 2021;16(3):S230. doi:https://doi.org/10.1016/j.jtho.2021.01.150
Passaro A, Cho BC, Wang Y, Melosky B, Califano R, Lee S-H, et al. Amivantamab plus chemotherapy (with or without lazertinib) vs chemotherapy in EGFR-mutated advanced NSCLC after progression on osimertinib: MARIPOSA-2, a phase III, global, randomized, controlled trial. Annals of Oncology. 2023;34:S1307. doi:https://doi.org/10.1016/j.annonc.2023.10.063
Pan B, Liang J, Shi H, Rao K, Guo W, Zhan C. Epidemiological characteristics and therapeutic advances of EGFR exon 20 insertion mutations in non-small cell lung cancer. Thorac Cancer. 2023;14(33):3247-3258. doi:10.1111/1759-7714.15127
O’Sullivan DE, Jarada TN, Yusuf A, Hu LXY, Gogna P, Brenner DR, et al. Prevalence, treatment patterns, and outcomes of individuals with EGFR positive metastatic non-small cell lung cancer in a Canadian real-world setting: a comparison of exon 19 deletion, L858R, and exon 20 insertion EGFR mutation carriers. Curr Oncol. 2022;29(10):7198-7208. doi:10.3390/curroncol29100567
Zhou C, Tang KJ, Cho BC, Liu B, Paz-Ares L, Cheng S, et al. Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions. N Engl J Med. 2023;389(22):2039-2051. doi:10.1056/NEJMoa2306441
Park K, Haura EB, Leighl NB, Mitchell P, Shu CA, Girard N, 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 Clin Oncol. 2021;39(30):3391-3402. doi:10.1200/jco.21.00662
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Canadian Oncology Today
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
