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Recent Patents on Anti-Cancer Drug Discovery

Author(s): Guixian Wu, Qian Chen, Dongqing Lv*, Ling Lin and Jing Huang

DOI: 10.2174/1574892818666230316145232

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Pulmonary Adenocarcinoma Patient with Complex Mutations on EGFR Benefits from Furmonertinib after Acquiring Gefitinib Resistance: A Case Report

Page: [247 - 252] Pages: 6

  • * (Excluding Mailing and Handling)

Abstract

Background: Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been proven a long-lasting treatment effect in pulmonary adenocarcinoma, most patients still progressed within one year due to the acquired resistance. Complex mutations of rare rare sites after acquiring resistance are rarely reported in pulmonary adenocarcinoma.

Case Presentation: A 62-year-old woman was diagnosed with pulmonary adenocarcinoma with stage IV. Genetic testing at the initial treatment showed EGFR L858R positive. After being treated with gefitinib, persistent 2 years disease progression occurred due to drug resistance. The genetic testing showed that EGFR L858R was eliminated, while a rare rare complex mutation of L861Q/G719X appeared. After 160 mg furmonertinib was treated for 1 month, the primary tumor regressed and the intracranial lesions disappeared. The patient has achieved progression-free survival (PFS) for more than 20 months.

Conclusion: Pulmonary adenocarcinoma with rare rare complex mutations in EGFR induced by gefitinib resistance and disease progression might benefit from furmonertinib treatment.

[1]
Singh T, Fatehi Hassanabad M, Fatehi Hassanabad A. Non-small cell lung cancer: Emerging molecular targeted and immunotherapeutic agents. Biochim Biophys Acta Rev Cancer 2021; 1876(2): 188636.
[http://dx.doi.org/10.1016/j.bbcan.2021.188636] [PMID: 34655692]
[2]
a) Wu SG, Shih JY. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer. Mol Cancer 2018; 17(1): 38.;
b) Iris GZ, Charles KJ, Paul LS, Lawrence WS. Combination of an EGFR t790m inhibitor and an EGFR inhibitor for the treatment of non-small cell lung cancer. Patent EP2968336A2, 2016.
[http://dx.doi.org/10.1186/s12943-018-0777-1] [PMID: 29455650]
[3]
Oyaert M, Demedts I, Boone E, et al. Antitumoral activity of tyrosine kinase inhibitors in patients with non-small cell lung cancer harbouring rare epidermal growth factor receptor mutations. Mol Diagn Ther 2015; 19(5): 267-72.
[http://dx.doi.org/10.1007/s40291-015-0158-z] [PMID: 26266520]
[4]
Passaro A, Mok T, Peters S, Popat S, Ahn MJ, de Marinis F. Recent advances on the role of EGFR tyrosine kinase inhibitors in the management of NSCLC with uncommon, non exon 20 insertions, EGFR mutations. J Thorac Oncol 2021; 16(5): 764-73.
[http://dx.doi.org/10.1016/j.jtho.2020.12.002]
[5]
a) Yang JCH, Sequist LV, Geater SL, 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.;
b) Gang Z, Zhigang L, Xiuwei G, et al. Application of curcumin and afatinib for combined treatment of non-small cell lung cancer. Patent CN105476996A, 2016.
[http://dx.doi.org/10.1016/S1470-2045(15)00026-1] [PMID: 26051236]
[6]
a) Cho JH, Lim SH, An HJ, et al. Osimertinib for patients with non-small-cell lung cancer harboring uncommon EGFR mutations: A multicenter, open-label, phase II trial (KCSG-LU15-09). J Clin Oncol 2020; 38(5): 488-95.;
b) Hua CB, Min LS. Method of treating epithelial growth factor receptor (EGFR) T790M-positive non-small cell lung cancer by administering a combination of a VEGFR-2 antibody and osimertinib. Patent US11471457B2, 2022.
[http://dx.doi.org/10.1200/JCO.19.00931] [PMID: 31825714]
[7]
Kanazu M, Mori M, Kimura M, et al. Effectiveness of EGFR tyrosine kinase inhibitors in advanced non‐small cell lung cancer patients with uncommon EGFR mutations: A multicenter observational study. Thorac Cancer 2021; 12(1): 90-6.
[http://dx.doi.org/10.1111/1759-7714.13718] [PMID: 33124128]
[8]
Moran T, Taus A, Arriola E, et al. Clinical activity of afatinib in patients with non-small-cell lung cancer harboring uncommon EGFR mutations: A spanish retrospective multicenter study. Clin Lung Cancer 2020; 21(5): 428-36.
[http://dx.doi.org/10.1016/j.cllc.2020.04.011] [PMID: 32461037]
[9]
Popat S, Hsia TC, Hung JY, et al. Tyrosine kinase inhibitor activity in patients with NSCLC harboring uncommon EGFR Mutations: A retrospective international cohort study (UpSwinG). Oncologist 2022; 27(4): 255-65.
[http://dx.doi.org/10.1093/oncolo/oyac022] [PMID: 35274704]
[10]
Zhang K, Yuan Q. Current mechanism of acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors and updated therapy strategies in human nonsmall cell lung cancer. J Cancer Res Ther 2016; 12(7): 131.
[http://dx.doi.org/10.4103/0973-1482.200613] [PMID: 28230005]
[11]
O’Kane GM, Bradbury PA, Feld R, et al. Uncommon EGFR mutations in advanced non-small cell lung cancer. Lung Cancer 2017; 109: 137-44.
[http://dx.doi.org/10.1016/j.lungcan.2017.04.016] [PMID: 28577943]
[12]
Hsu WH, Yang JCH, Mok TS, Loong HH. Overview of current systemic management of EGFR-mutant NSCLC. Ann Oncol 2018; 29 (Suppl. 1): i3-9.
[http://dx.doi.org/10.1093/annonc/mdx702] [PMID: 29462253]
[13]
Harrison PT, Vyse S, Huang PH. Rare Epidermal Growth Factor Receptor (EGFR) mutations in non-small cell lung cancer. Semin Cancer Biol 2020; 61: 167-79.
[http://dx.doi.org/10.1016/j.semcancer.2019.09.015] [PMID: 31562956]
[14]
Chiu CH, Yang CT, Shih JY, et al. Epidermal growth factor receptor tyrosine kinase inhibitor treatment response in advanced lung adenocarcinomas with G719X/L861Q/S768I mutations. J Thorac Oncol 2015; 10(5): 793-9.
[http://dx.doi.org/10.1097/JTO.0000000000000504]
[15]
Banno E, Togashi Y, Nakamura Y, et al. Sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors of uncommon epidermal growth factor receptor mutations L861Q and S768I: What is the optimal epidermal growth factor receptor‐tyrosine kinase inhibitor? Cancer Sci 2016; 107(8): 1134-40.
[http://dx.doi.org/10.1111/cas.12980] [PMID: 27240419]
[16]
Yang JCH, Schuler M, Popat S, et al. Afatinib for the treatment of non-small cell lung cancer harboring uncommon EGFR mutations: An updated database of 1023 cases brief report. Front Oncol 2022; 12: 834704.
[http://dx.doi.org/10.3389/fonc.2022.834704] [PMID: 35574304]
[17]
Floc’h N, Lim S, Bickerton S, et al. Osimertinib, an irreversible next-generation EGFR tyrosine kinase inhibitor, exerts antitumor activity in various preclinical NSCLC models harboring the uncommon EGFR mutations G719X or L861Q or S768I. Mol Cancer Ther 2020; 19(11): 2298-307.
[http://dx.doi.org/10.1158/1535-7163.MCT-20-0103] [PMID: 32943544]
[18]
Deeks ED. Furmonertinib: First approval. Drugs 2021; 81(15): 1775-80.
[http://dx.doi.org/10.1007/s40265-021-01588-w] [PMID: 34528187]
[19]
Musib L, Kowanetz M, Li Q, et al. Furmonertinib is an oral, irreversible, highly brain-penetrant pan-EGFR mutant inhibitor with activity against classical and atypical EGFR mutations. Presented at the North American Conference in Lung Cancer September 23, 2022 to September 25, 2022 Chicago, Illinois, USA.