Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Correlation Analysis between T790M Status and Clinical Characteristics of Patients with EGFR-sensitive Mutation Advanced NSCLC who Progressed after the First Generation and First-line EGFR-TKIs Administration: A Real-world Exploratory Study

Author(s): Ye Zhen, Ying-Bo Xu, Ruo-Ying Deng, Meng Li, Min-Ting Ma, Zhi-Guo Zhou, Qing-Ju Meng*, Ya-Ning Gong, Li-Yan Zhao and Yi-Bing Liu*

Volume 27, Issue 6, 2024

Published on: 19 July, 2023

Page: [845 - 853] Pages: 9

DOI: 10.2174/1386207326666230606100729

Price: $65

Abstract

Aim: The present study is to investigate the association between T790M status and clinical characteristics of patients with EGFR-sensitive advanced non-small cell lung cancer (NSCLC) who progressed the initial epidermal growth factor receptor tyrosine kinase inhibitors (EGFRTKIs) administration.

Methods: A total of 167 patients with EGFR-sensitive mutations advanced NSCLC who had successful genetic tests and progressed the initial EGFR-TKI treatment were included in this study retrospectively. The clinical and demographic characteristics of these patients were collected, which were manifested as pathological type, metastasis location, initial biopsy method, initial genetic test specimens, and baseline gene mutations status. Correlation analysis between T790M status and these characteristics was performed and prognostic analysis regarding the different subgroups was carried out accordingly.

Results: The prevalence of secondary T790M after resistance to initial EGFR-TKIs among the 167 patients was 52.7%. Correlation analysis indicated that the median progression-free Survival (PFS) to initial EGFR-TKIs >12 months were more likely to develop secondary T790M in univariate analysis. However, the conclusion failed to show statistically significant in multivariate analysis. Additionally, patients with intracranial progression of initial EGFR-TKIs therapy were associated with secondary EGFR-T790M. However, it should be noted that those whose best overall response was partial response (PR) during the EGFR-TKI therapy were relevant to secondary T790M. Furthermore, The median PFS of the initial EGFR-TKIs administration was longer among patients with T790M positive mutation and patients with PR reaction than those without T790M mutation and patients with stable disease (SD), respectively (median PFS: 13.6 vs. 10.9 months, P=0.023) and (median PFS: 14.0 vs. 10.1 months, P=0.001).

Conclusion: This retrospective study highlighted the real-world evidence that the best efficacy and intracranial progression with initial EGFR-TKIs therapy among patients with advanced NSCLC might be the promising indicators to predict the occurrence of EGFR-T790M. Patients with PR reaction and T790M positive mutation conferred longer PFS of the initial EGFR-TKIs administration. Also, the conclusion should be confirmed in more patients with advanced NSCLC subsequently.

« Previous Next »
[1]
Wu, F.; Wang, L.; Zhou, C. Lung cancer in China: current and prospect. Curr. Opin. Oncol., 2021, 33(1), 40-46.
[http://dx.doi.org/10.1097/CCO.0000000000000703] [PMID: 33165004]
[2]
Ramalingam, S.S.; Owonikoko, T.K.; Khuri, F.R. Lung cancer: New biological insights and recent therapeutic advances. CA Cancer J. Clin., 2011, 61(2), 91-112.
[http://dx.doi.org/10.3322/caac.20102] [PMID: 21303969]
[3]
Zhang, J.; Mao, W.; Chen, Z.; Gu, H.; Lian, C. Clinical significance of Has_circ_0060937 in bone metastasis of NSCLC. Int. J. Gen. Med., 2020, 13, 1115-1121.
[http://dx.doi.org/10.2147/IJGM.S279023]
[4]
Paz-Ares, L.; Tan, E.H.; O’Byrne, K.; Zhang, L.; Hirsh, V.; Boyer, M.; Yang, J.C.H.; Mok, T.; Lee, K.H.; Lu, S.; Shi, Y.; Lee, D.H.; Laskin, J.; Kim, D.W.; Laurie, S.A.; Kölbeck, K.; Fan, J.; Dodd, N.; Märten, A.; Park, K. 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., 2017, 28(2), 270-277.
[http://dx.doi.org/10.1093/annonc/mdw611] [PMID: 28426106]
[5]
Maemondo, M.; Inoue, A.; Kobayashi, K.; Sugawara, S.; Oizumi, S.; Isobe, H.; Gemma, A.; Harada, M.; Yoshizawa, H.; Kinoshita, I.; Fujita, Y.; Okinaga, S.; Hirano, H.; Yoshimori, K.; Harada, T.; Ogura, T.; Ando, M.; Miyazawa, H.; Tanaka, T.; Saijo, Y.; Hagiwara, K.; Morita, S.; Nukiwa, T. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N. Engl. J. Med., 2010, 362(25), 2380-2388.
[http://dx.doi.org/10.1056/NEJMoa0909530] [PMID: 20573926]
[6]
Saito, H.; Fukuhara, T.; Furuya, N.; Watanabe, K.; Sugawara, S.; Iwasawa, S.; Tsunezuka, Y.; Yamaguchi, O.; Okada, M.; Yoshimori, K.; Nakachi, I.; Gemma, A.; Azuma, K.; Kurimoto, F.; Tsubata, Y.; Fujita, Y.; Nagashima, H.; Asai, G.; Watanabe, S.; Miyazaki, M.; Hagiwara, K.; Nukiwa, T.; Morita, S.; Kobayashi, K.; Maemondo, M. 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., 2019, 20(5), 625-635.
[http://dx.doi.org/10.1016/S1470-2045(19)30035-X] [PMID: 30975627]
[7]
Zhang, Y.; Zeng, Y.; Liu, T.; Du, W.; Zhu, J.; Liu, Z.; Huang, J. The canonical TGF-β/Smad signalling pathway is involved in PD-L1-induced primary resistance to EGFR-TKIs in EGFR-mutant non-small-cell lung cancer. Respir. Res., 2019, 20(1), 164.
[http://dx.doi.org/10.1186/s12931-019-1137-4] [PMID: 31331328]
[8]
Oxnard, G.R.; Arcila, M.E.; Sima, C.S.; Riely, G.J.; Chmielecki, J.; Kris, M.G.; Pao, W.; Ladanyi, M.; Miller, V.A. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin. Cancer Res., 2011, 17(6), 1616-1622.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-2692] [PMID: 21135146]
[9]
Ma, G.; Zhang, J.; Jiang, H.; Zhang, N.; Yin, L.; Li, W.; Zhou, Q. Epidermal growth factor receptor T790M mutation as a prognostic factor in EGFR-mutant non-small cell lung cancer patients that acquired resistance to EGFR tyrosine kinase inhibitors. Oncotarget, 2017, 8(59), 99429-99437.
[http://dx.doi.org/10.18632/oncotarget.19681] [PMID: 29245913]
[10]
Chougule, A.; Basak, S. Epidermal growth factor receptor T790M testing in progressed lung cancer: A review of sensitive methods for analysis of tissue and liquid biopsy samples. Indian J. Cancer, 2017, 54(5)(Suppl.), 45.
[http://dx.doi.org/10.4103/ijc.IJC_540_17] [PMID: 29292708]
[11]
Li, Z.; Zhang, Y.; Bao, W.; Jiang, C. Insufficiency of peripheral blood as a substitute tissue for detecting EGFR mutations in lung cancer: a meta-analysis. Target. Oncol., 2014, 9(4), 381-388.
[http://dx.doi.org/10.1007/s11523-014-0312-2] [PMID: 24623059]
[12]
Zhang, S.; Zhu, L.; Xia, B.; Chen, E.; Zhao, Q.; Zhang, X.; Chen, X.; Chen, X.; Ma, S. Epidermal growth factor receptor (EGFR) T790M mutation identified in plasma indicates failure sites and predicts clinical prognosis in non-small cell lung cancer progression during first-generation tyrosine kinase inhibitor therapy: a prospective observat. Cancer Commun. (Lond.), 2018, 38(1), 28.
[http://dx.doi.org/10.1186/s40880-018-0303-2] [PMID: 29789021]
[13]
Sequist, L.V.; Waltman, B.A.; Dias-Santagata, D.; Digumarthy, S.; Turke, A.B.; Fidias, P.; Bergethon, K.; Shaw, A.T.; Gettinger, S.; Cosper, A.K.; Akhavanfard, S.; Heist, R.S.; Temel, J.; Christensen, J.G.; Wain, J.C.; Lynch, T.J.; Vernovsky, K.; Mark, E.J.; Lanuti, M.; Iafrate, A.J.; Mino-Kenudson, M.; Engelman, J.A. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci. Transl. Med., 2011, 3(75), 75ra26.
[http://dx.doi.org/10.1126/scitranslmed.3002003] [PMID: 21430269]
[14]
Hata, A.; Katakami, N.; Yoshioka, H.; Kaji, R.; Masago, K.; Fujita, S.; Imai, Y.; Nishiyama, A.; Ishida, T.; Nishimura, Y.; Yatabe, Y. Spatiotemporal T790M Heterogeneity in Individual Patients with EGFR-Mutant Non–Small-Cell Lung Cancer after Acquired Resistance to EGFR-TKI. J. Thorac. Oncol., 2015, 10(11), 1553-1559.
[http://dx.doi.org/10.1097/JTO.0000000000000647] [PMID: 26309190]
[15]
Hata, A.; Katakami, N.; Yoshioka, H.; Takeshita, J.; Tanaka, K.; Masago, K.; Fujita, S.; Kaji, R.; Imai, Y.; Monden, K.; Matsumoto, T.; Nagata, K.; Otsuka, K.; Tachikawa, R.; Tomii, K.; Kunimasa, K.; Iwasaku, M.; Nishiyama, A.; Ishida, T.; Nishimura, Y. Prognostic impact of central nervous system metastases after acquired resistance to EGFR-TKI: poorer prognosis associated with T790M-negative status and leptomeningeal metastases. Anticancer Res., 2015, 35(2), 1025-1031. [doi].
[PMID: 25667490]
[16]
Yoshimura, A.; Yamada, T.; Okura, N.; Takeda, T.; Furutani, W.; Kubota, Y.; Shiotsu, S.; Hiranuma, O.; Nishioka, N.; Chihara, Y.; Tamiya, N.; Kaneko, Y.; Uchino, J.; Takayama, K. The impact of the tumor shrinkage by initial EGFR inhibitors according to the detection of EGFR-T790M mutation in patients with non-small cell lung cancer harboring EGFR mutations. BMC Cancer, 2018, 18(1), 1241.
[http://dx.doi.org/10.1186/s12885-018-5153-4] [PMID: 30537950]
[17]
Oya, Y.; Yoshida, T.; Kuroda, H.; Shimizu, J.; Horio, Y.; Sakao, Y.; Inaba, Y.; Hida, T.; Yatabe, Y. Association Between EGFR T790M Status and Progression Patterns During Initial EGFR-TKI Treatment in Patients Harboring EGFR Mutation. Clin. Lung Cancer, 2017, 18(6), 698-705.e2.
[http://dx.doi.org/10.1016/j.cllc.2017.05.004] [PMID: 28596108]
[18]
Matsuo, N.; Azuma, K.; Sakai, K.; Hattori, S.; Kawahara, A.; Ishii, H.; Tokito, T.; Kinoshita, T.; Yamada, K.; Nishio, K. Hoshino, T Association of EGFR exon 19 deletion and EGFR-TKI treatment duration with frequency of t790m Mutation in EGFR-mutant lung cancer patients. Sci. Rep., 2016, 6, 36458.
[http://dx.doi.org/10.1038/srep36458] [PMID: 27811988]
[19]
Gaut, D.; Sim, M.S.; Yue, Y.; Wolf, B.R.; Abarca, P.A.; Carroll, J.M.; Goldman, J.W.; Garon, E.B. Clinical implications of the T790M mutation in disease characteristics and treatment response in patients with Epidermal Growth Factor Receptor (EGFR)-Mutated Non–Small-Cell Lung Cancer (NSCLC). Clin. Lung Cancer, 2018, 19(1), e19-e28.
[http://dx.doi.org/10.1016/j.cllc.2017.06.004] [PMID: 28712979]
[20]
Kawamura, T.; Kenmotsu, H.; Omori, S.; Nakashima, K.; Wakuda, K.; Ono, A.; Naito, T.; Murakami, H.; Omae, K.; Mori, K.; Tanigawara, Y.; Nakajima, T.; Ohde, Y.; Endo, M.; Takahashi, T. Clinical factors predicting detection of T790M mutation in rebiopsy for EGFR-mutant non–small-cell lung cancer. Clin. Lung Cancer, 2018, 19(2), e247-e252.
[http://dx.doi.org/10.1016/j.cllc.2017.07.002] [PMID: 28866043]
[21]
Chmielecki, J.; Foo, J.; Oxnard, G.R.; Hutchinson, K.; Ohashi, K.; Somwar, R.; Wang, L.; Amato, K.R.; Arcila, M.; Sos, M.L.; Socci, N.D.; Viale, A.; de Stanchina, E.; Ginsberg, M.S.; Thomas, R.K.; Kris, M.G.; Inoue, A.; Ladanyi, M.; Miller, V.A.; Michor, F.; Pao, W. Optimization of dosing for EGFR-mutant non-small cell lung cancer with evolutionary cancer modeling. Sci. Transl. Med., 2011, 3(90), 90ra59.
[http://dx.doi.org/10.1126/scitranslmed.3002356] [PMID: 21734175]
[22]
Iwama, E.; Takayama, K.; Harada, T.; Okamoto, I.; Ookubo, F.; Kishimoto, J.; Baba, E.; Oda, Y.; Nakanishi, Y. Highly sensitive and quantitative evaluation of the EGFR T790M mutation by nanofluidic digital PCR. Oncotarget, 2015, 6(24), 20466-20473.
[http://dx.doi.org/10.18632/oncotarget.4058] [PMID: 26015401]
[23]
Zheng, D.; Ye, X.; Zhang, M.Z.; Sun, Y.; Wang, J.Y.; Ni, J.; Zhang, H.P.; Zhang, L.; Luo, J.; Zhang, J.; Tang, L.; Su, B.; Chen, Z.; Zhu, G.; Gu, Y.; Xu, J.F. Plasma EGFR T790M ctDNA status is associated with clinical outcome in advanced NSCLC patients with acquired EGFR-TKI resistance. Sci. Rep., 2016, 6, 20913.
[http://dx.doi.org/10.1038/srep20913] [PMID: 26867973]
[24]
Kuiper, J.L.; Heideman, D.A.M.; Thunnissen, E.; Paul, M.A.; van Wijk, A.W.; Postmus, P.E.; Smit, E.F. Incidence of T790M mutation in (sequential) rebiopsies in EGFR-mutated NSCLC-patients. Lung Cancer, 2014, 85(1), 19-24.
[http://dx.doi.org/10.1016/j.lungcan.2014.03.016] [PMID: 24768581]
[25]
Norkowski, E.; Ghigna, M.R.; Lacroix, L.; Le Chevalier, T.; Fadel, É.; Dartevelle, P.; Dorfmuller, P.; Thomas de Montpréville, V. Small-cell carcinoma in the setting of pulmonary adenocarcinoma: New insights in the era of molecular pathology. J. Thorac. Oncol., 2013, 8(10), 1265-1271.
[http://dx.doi.org/10.1097/JTO.0b013e3182a407fa] [PMID: 24457237]
[26]
Haratani, K.; Hayashi, H.; Watanabe, S.; Kaneda, H.; Yoshida, T.; Takeda, M.; Shimizu, T.; Nakagawa, K. Two cases of EGFR mutation-positive lung adenocarcinoma that transformed into squamous cell carcinoma: Successful treatment of one case with rociletinib. Ann. Oncol., 2016, 27(1), 200-202.
[http://dx.doi.org/10.1093/annonc/mdv495] [PMID: 26483048]
[27]
Yamaguchi, F.; Kato, E.; Wakabayashi, A.; Shikama, Y. Effect of osimertinib treatment on lung adenocarcinoma with squamous cell transformation harboring the T790M mutation: A case report and literature review. Mol. Clin. Oncol., 2019, 11(2), 127-131.
[http://dx.doi.org/10.3892/mco.2019.1880] [PMID: 31316771]
[28]
Lee, K.; Kim, Y.; Jung, H.A.; Lee, S.H.; Ahn, J.S.; Ahn, M.J.; Park, K.; Choi, Y.L.; Sun, J.M. Repeat biopsy procedures and T790M rates after afatinib, gefitinib, or erlotinib therapy in patients with lung cancer. Lung Cancer, 2019, 130, 87-92.
[http://dx.doi.org/10.1016/j.lungcan.2019.01.012] [PMID: 30885357]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy