CLINICAL, PARACLINICAL FEATURES AND IDENTIFICATION OF EGFR-T790M MUTATIONS CAUSING FIRST-GENERATION EGFR-TKIS RESISTANCE IN PATIENTS WITH NON-SMALL CELL LUNG CANCER BY USING LIQUID BIOPSY

Hữu Hoàng Hải Hà 1,, Hoàn Lê1,2, Khánh Chi Trần1,2, Thị Như Quỳnh Nguyễn3
1 Hanoi medical university
2 Hanoi medical university hospital
3 Hanoi medical univerity hospital

Main Article Content

Abstract

Objectives: To investigate clinical and laboratory characteristics to determine the status of EGFR-T790M mutations causing first-generation resistance to EGFR-TKIs in patients with non-small cell lung cancer by liquid biopsy technique. Subjects: Including 31 patients diagnosed with EGFR-mutated non-small cell lung cancer (+) who received first-step treatment with first-generation EGFR-TKIs, and had liquid biopsies for EGFR-T790M mutations. Result: The study patients were mainly over 60 years old (64.5%) in which the male: female ratio was approximately equal; up to 58.1% of the patients did not smoke. The mean time of emergence of resistance to 1st generation TKIs: 11.9 ± 3.4 months (ranged from 7-20 months). Fatigue (96.8%) and weight loss (87.1%) were systemic symptoms accounting for the highest proportion. Chest pain (77.4%) was the most common respiratory symptom; hemoptysis (12.9%) was the least common. The number of patients with tumor sizes from 2-3cm is the highest, accounting for 32.3%, up to 9.7% of patients with tumor size >7cm. EGFR-T790M mutations detected by liquid biopsy method was 35.5%; up to 64.5% of patients had advanced disease, but liquid biopsy results did not have EGFR-T790M gene mutations. Median progression-free survival between the group carrying the EGFR-T790M mutation (11.82 months; 95% CI 9.22-14.42) and the group not carrying the EGFR-T790M mutation (11.95 months); 95%CI 10.44-13.46) there was no statistically significant difference. Conclusion: The rate of patients with EGFR-T790M mutation by liquid biopsy is somewhat higher than in other studies worldwide. No factors affecting the occurrence of EGFR-T790M mutations have been recorded, nor have they been recorded for this mutation.

Article Details

References

1. Kuiper JL, Heideman DA, Thunnissen E, et al. Incidence of T790M mutation in (sequential) rebiopsies in EGFR-mutated NSCLC-patients. Lung Cancer. Jul 2014;85(1):19-24. doi:10.1016/ j.lungcan.2014.03.016
2. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol. Sep 2015;10(9):1243-1260. doi:10.1097/JTO.0000000000000630
3. Pallis A, Serfass L, Dziadziuszko R, et al. Targeted therapies in the treatment of advanced/metastatic NSCLC. European journal of cancer. 2009;45(14):2473-2487.
4. Jenkins S, Yang JC, Ramalingam SS, et al. Plasma ctDNA Analysis for Detection of the EGFR T790M Mutation in Patients with Advanced Non-Small Cell Lung Cancer. J Thorac Oncol. Jul 2017;12(7):1061-1070. doi:10.1016/j.jtho.2017.04.003
5. Wang Z-F, Ren S-X, Li W, Gao G-H. 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. 2018;18(1):1-7.
6. Kim H-R, Lee JC, Kim Y-C, et al. Clinical characteristics of non-small cell lung cancer patients who experienced acquired resistance during gefitinib treatment. Lung Cancer. 2014; 83(2):252-258.
7. Oxnard GR, Arcila ME, Sima CS, et al. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clinical cancer research. 2011;17(6):1616-1622.
8. Oya Y, Yoshida T, Kuroda H, et al. Association between EGFR T790M status and progression patterns during initial EGFR-TKI treatment in patients harboring EGFR mutation. Clinical lung cancer. 2017;18(6):698-705. e2.