Detection of EGFR-Activating and T790M Mutations Using Liquid Biopsy in Patients With EGFR-Mutated Non–Small-Cell Lung Cancer Whose Disease Has Progressed During Treatment With First- and Second-Generation Tyrosine Kinase Inhibitors: A Multicenter Real-Life Retrospective Study

Minari, Roberta; Mazzaschi, Giulia; Bordi, Paola; Gnetti, Letizia; Alberti, Giorgia; Altimari, Annalisa; Gruppioni, Elisa; Sperandi, Francesca; Parisi, Claudia; Guaitoli, Giorgia; Bettelli, Stefania; Longo, Lucia; Bertolini, Federica; Pagano, Maria; Bonelli, Candida; Tagliavini, Elena; Nicoli, Davide; Ubiali, Alessandro; Zangrandi, Adriano; Trubini, Serena; Proietto, Manuela; Fiorentino, Michelangelo; Tiseo, Marcello

doi:10.1016/j.cllc.2020.02.021

Cited by 25 publications

(21 citation statements)

References 30 publications

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“…The detection rate of T790M following first-and second-generation EGFR TKIs varies from study-to-study but most analyses indicate a detection rate of around 50-70% [74,75]. Use of liquid biopsies and sensitive detection assays can complement tissue-based tests and help optimize the detection of T790M even when present in a small number of tumor cells [76][77][78][79]. Furthermore, some studies suggest that the detection rate of T790M is particularly high in patients with a Del19 mutation (73%) [80].…”

Section: Future Perspectivementioning

confidence: 99%

Egfr Tyrosine Kinase Inhibitors for EGFR Mutation-Positive Non-Small-Cell Lung Cancer: Outcomes in Asian Populations

Kim

Melosky²,

Park

et al. 2021

Future Oncol.

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Few data are available that have compared outcomes with different EGFR tyrosine kinase inhibitors (TKIs) specifically in Asian patients with EGFR mutation-positive non-small-cell lung cancer. In this narrative review, we have collated available data from prospective studies that have assessed first-, second- and third-generation EGFR TKIs in Asian populations, including subanalyses in individual countries (China and Japan). These data indicate that outcomes with first- and second-generation TKIs are broadly similar in Asian and non-Asian populations. However, while the third-generation EGFR TKI, osimertinib, confers significant overall survival benefit over erlotinib/gefitinib in non-Asians, this is not apparent in Asians, particularly in countries like Japan with well-resourced healthcare. Head-to-head comparisons of second- and third-generation EGFR TKIs, with OS as a primary end point, should be considered in Asia.

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Section: Future Perspectivementioning

confidence: 99%

Egfr Tyrosine Kinase Inhibitors for EGFR Mutation-Positive Non-Small-Cell Lung Cancer: Outcomes in Asian Populations

Kim

Melosky²,

Park

et al. 2021

Future Oncol.

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“…Tissue or plasma‐based liquid biopsy is a routine approach used for detecting p.T790 M mutation in patients with acquired resistance to first or second‐generation EGFR‐TKIs 4,5 . Due to safety and increased complication risks during tumor tissue re‐biopsy, plasma‐based liquid biopsy is preferred 6 .…”

Section: Introductionmentioning

confidence: 99%

Sputum cell‐free DNA: Valued surrogate sample for the detection of EGFR exon 20 p.T790M mutation in patients with advanced lung adenocarcinoma and acquired resistance to EGFR‐TKIs

Wang

Zhang

et al. 2021

Cancer Medicine

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BackgroundSputum cell‐free DNA (cfDNA) is a valuable surrogate sample for assessing EGFR‐sensitizing mutations in patients with advanced lung adenocarcinoma. Detecting EGFR exon 20 p.T790 M (p.T790 M) is much more challenging due to its limited availability in tumor tissues. Exploring sputum cfDNA as an alternative for liquid‐based sample type in detecting p.T790 M requires potential improvement in clinical practice.MethodsA total of 34 patients with EGFR‐sensitive mutation‐positive lung adenocarcinoma and acquired resistance to the first generation of epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) were enrolled. The sputum samples, and paired tumors and/or plasma samples were tested for p.T790 M mutation and concordance of p.T790 M status among the three sample types was analyzed.ResultsThe overall concordance rate of p.T790 M mutation between sputum cfDNA and tumor tissue samples was 85.7%, with a sensitivity of 66.7% and a specificity of 100%. The sensitivity for detecting p.T790 M in sputum cfDNA was 100%, 66.7%, and 0% in the three sputum groups of malignant, satisfactory but no malignant cells, and unsatisfactory, respectively. The combined results of plasma cfDNA testing and sputum cfDNA testing further increased the sensitivity to 100% for p.T790 M detection in satisfactory but no malignant cells sputum group.ConclusionThese findings revealed that cfDNA from malignant or satisfied but no malignant cells sputum is considered suitable for detecting p.T790 M mutation in patients with acquired resistance to first or second‐generation EGFR‐TKIs. The sputum cytological pathological evaluation‐guided sputum cfDNA testing assists in significantly improving the sensitivity of p.T790 M detection, bringing significant value for the maximal application of third‐generation EGFR‐TKIs in second‐line treatment.

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“…Randomized clinical trials reported T790M in about 50–60% of the patients, using both liquid and tissue biopsies [ 7 , 20 ]. Real word data reported a T790M detection rate through liquid biopsy of about 25%, using real-time PCR based tests, while it reached 66% using ddPCR [ 21 , 22 , 23 , 24 ]. Performing liquid biopsy at first hints of possible TKI resistance, and performing before clinical or canonical radiological PD may have further lowered T790M detectability in our cohort [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Real word data reported a T790M detection rate through liquid biopsy of about 25%, using real-time PCR based tests, while it reached 66% using ddPCR [ 21 , 22 , 23 , 24 ]. Performing liquid biopsy at first hints of possible TKI resistance, and performing before clinical or canonical radiological PD may have further lowered T790M detectability in our cohort [ 21 ]. In the present survey, repeating liquid biopsy in case of a first negative result emerged as a common practice (1.63 biopsies for each patient).…”

Section: Discussionmentioning

confidence: 99%

A Multi-Center, Real-Life Experience on Liquid Biopsy Practice for EGFR Testing in Non-Small Cell Lung Cancer (NSCLC) Patients

Cortiula

Pasello

Follador³

et al. 2020

Diagnostics

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Background: circulating tumor DNA (ctDNA) is a source of tumor genetic material for EGFR testing in NSCLC. Real-word data about liquid biopsy (LB) clinical practice are lacking. The aim of the study was to describe the LB practice for EGFR detection in North Eastern Italy. Methods: we conducted a multi-regional survey on ctDNA testing practices in lung cancer patients. Results: Median time from blood collection to plasma separation was 50 min (20–120 min), median time from plasma extraction to ctDNA analysis was 24 h (30 min–5 days) and median turnaround time was 24 h (6 h–5 days). Four hundred and seventy five patients and 654 samples were tested. One hundred and ninety-two patients were tested at diagnosis, with 16% EGFR mutation rate. Among the 283 patients tested at disease progression, 35% were T790M+. Main differences in LB results between 2017 and 2018 were the number of LBs performed for each patient at disease progression (2.88 vs. 1.2, respectively) and the percentage of T790M+ patients (61% vs. 26%).

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Detection of EGFR-Activating and T790M Mutations Using Liquid Biopsy in Patients With EGFR-Mutated Non–Small-Cell Lung Cancer Whose Disease Has Progressed During Treatment With First- and Second-Generation Tyrosine Kinase Inhibitors: A Multicenter Real-Life Retrospective Study

Cited by 25 publications

References 30 publications

Egfr Tyrosine Kinase Inhibitors for EGFR Mutation-Positive Non-Small-Cell Lung Cancer: Outcomes in Asian Populations

Egfr Tyrosine Kinase Inhibitors for EGFR Mutation-Positive Non-Small-Cell Lung Cancer: Outcomes in Asian Populations

Sputum cell‐free DNA: Valued surrogate sample for the detection of EGFR exon 20 p.T790M mutation in patients with advanced lung adenocarcinoma and acquired resistance to EGFR‐TKIs

A Multi-Center, Real-Life Experience on Liquid Biopsy Practice for EGFR Testing in Non-Small Cell Lung Cancer (NSCLC) Patients

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