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Vol. 27. Issue 5.
Pages 472-473 (September - October 2021)
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Vol. 27. Issue 5.
Pages 472-473 (September - October 2021)
Letter to the Editor
DOI: 10.1016/j.pulmoe.2021.01.007
Open Access
T790M-EGFR mutation frequency in advanced NSCLC patients on progression from a previous TKI therapy: results from a Portuguese study
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Encarnação Teixeiraa,
Corresponding author
encarnacaoteixeira@gmail.com

Corresponding author.
a Hospital Pulido Valente, Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal
António Araújob
b Hospital de Santo António, Centro Hospitalar Universitário do Porto, Porto, Portugal
Venceslau Hespanholc
c Centro Hospitalar Universitário de São João, Porto, Portugal
Bárbara Parented
d Hospital CUF Porto, Porto, Portugal
Fernando Baratae
e Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal
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Table 1. Frequency of T790 M mutation by method.
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The current treatment for advanced non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations is centered around EGFR-tyrosine kinase inhibitors (EGFR-TKIs).1,2 However, resistance to EGFR-TKIs frequently develops. Multiple reports have shown that the T790 M mutation is present in approximately half the patients who develop resistance to a first- or second-generation EGFR-TKIs. Osimertinib is approved for the treatment of NSCLC harboring T790 M, highlighting the clinical relevance of the detection of this mutation.3 Genotyping for EGFR T790 M initially required a tissue biopsy, with its inherent risks and possible treatment delay. More recently, noninvasive genotyping of cell-free plasma DNA emerged as a safer and faster alternative for detection of EGFR T790M.4 There was no previous data on the prevalence of T790 M mutation in the Portuguese patients with advanced NSCLC. Therefore, the objective of this study was to determine the frequency of this mutation in patients with advanced NSCLC.

This prospective, analytical, multicenter study included 40 adult patients with locally advanced or metastatic NSCLC treated at 13 Portuguese oncology centers, from November 2017 to March 2019, and who had progressed or discontinued due to adverse effects following therapy or after two or more lines of treatment with EGFR-TKI and chemotherapy. The presence of T790M-EGFR mutation was assessed both in tissue and blood biopsy. Blood samples were analyzed by Ampliseq™ EGFR Hot Spots NGS panel from Thermo Fisher, cobas® EGFR Mutation Test v2 US-IVD from Roche Molecular Diagnostics and digital PCR EGFR T790 M by Thermo Fisher. All patients signed an informed consent form, and the study was previously evaluated and approved by the Ethics Committee of the participating sites.

Patients median age was 69 years (interquartile range 62–74.25 years) and 65% were females. Prior to sample collection, 32 (80%) subjects had received treatment with EGFR-TKIs, 7 (17.5%) had had chemotherapy and EGFR-TKIs, and one received EGFR-TKIs, chemotherapy and immunotherapy. Thirty-nine patients had conclusive results for liquid biopsy (one subject did not perform tissue biopsy and had an inconclusive result in liquid biopsy) and 12 patients for tissue biopsy.

The frequency of T790 M mutation was 44% (95% CI: 28−59%), Table 1.

Table 1.

Frequency of T790 M mutation by method.

Frequency of T790 M mutation by method  Relative frequency(%) [CI 95%] (n/total) 
At least one positive biopsy  44% [28−59%] (17/39) 
Positive in tissue biopsy  42% [14−70%] (5/12) 
Positive in liquid biopsy  36% [21−51%] (14/39) 

This study was limited by the low recruitment rate that implied the end of the study with 40 patients instead of the target sample of 155 subjects. Moreover, only 12 samples were obtained for tissue biopsy. For these reasons, it was not possible to draw statistically significant conclusions regarding our secondary objectives, namely the concordance between liquid vs. tissue biopsy, and the comparison between techniques for determining the T790 M mutation of the EGFR gene in liquid biopsy.

Nonetheless, the frequency of T790 M mutation in the target population was comparable to that reported in the literature5 which underlines the relevance of the testing.

In Portugal, the criteria for EGFR genetic screening varies between medical institutions and it is still not a routine assessment in clinical practice. These results, as well our unforeseen low recruitment, highlight the importance of issuing guidelines and implementing them in current practice.

Conflicts of interest

The authors have no conflicts of interest to declare.

Funding

This work was supported by AstraZeneca-Produtos Farmacêuticos, Lda.

Acknowledgments

We thank all the participating investigators for their contribution in data collection, and patient selection/evaluation during the study: Dr. Gabriela Fernandes, Prof. Dr. António Araújo, Dr. Bárbara Parente, Dr. Ana Barroso, Dr. Ulisses Brito, Dr. José Albino Lopes, Dr. Lourdes Barradas, Dr. Marcos Pantarotto, Dr. Margarida Felizardo, Dr. Ricardo Luz, Dr. António Meleiro, and Dr. Fernando Barata.

References
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H. Kimura, Y. Amino, H. Koba, Y. Tambo, N. Ohkura, J. Hara, et al.
A case of EGFR mutation-positive lung adenocarcinoma in which the T790M allele fraction was increased by repeated EGFR-TKI treatment.
Cancer Commun [Internet], 39 (2019), pp. 67
[2]
G.R. Oxnard, M.E. Arcila, C.S. Sima, G.J. Riely, J. Chmielecki, M.G. Kris, 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.
Clin cancer Res, 17 (2011), pp. 1616-1622
[3]
D. Zheng, X. Ye, M.Z. Zhang, Y. Sun, J.Y. Wang, J. Ni, et al.
Plasma EGFR T790M ctDNA status is associated with clinical outcome in advanced NSCLC patients with acquired EGFR-TKI resistance.
Sci Rep, 6 (2016), pp. 20913
[4]
G.R. Oxnard, K.S. Thress, R.S. Alden, R. Lawrance, C.P. Paweletz, M. Cantarini, et al.
Association between plasma genotyping and outcomes of treatment with osimertinib (AZD9291) in advanced non-small-cell lung cancer.
J Clin Oncol, 34 (2016), pp. 3375-3382
[5]
L.V. Sequist, B.A. Waltman, D. Dias-Santagata, S. Digumarthy, A.B. Turke, P. Fidias, et al.
Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors.
Sci Transl Med, 3 (2011),
Pulmonology

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