Clinical Features and Progression Pattern of Acquired T790M-positive Compared With T790M-negative EGFR Mutant Non–small-cell Lung Cancer: Catching Tumor and Clinical Heterogeneity Over Time Through Liquid Biopsy

Maso, Alessandro Dal; Roca, Elisa; Pilotto, Sara; Macerelli, Marianna; Polo, Valentina; Cecere, Fabiana Letizia; Conte, Alessandro Del; Nardo, Giorgia; Buoro, Vanessa; Scattolin, Daniela; Monteverdi, Sara; Urso, Loredana; Zulato, Elisabetta; Frega, Stefano; Bonanno, Laura; Calabrese, Fiorella; Conte, Pier Franco; Pasello, Giulia

doi:10.1016/j.cllc.2019.07.009

Cited by 20 publications

(32 citation statements)

References 60 publications

(97 reference statements)

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“…Furthermore, the cobas plasma test that detects EGFR mutations has demonstrated acceptable agreement between plasma and tissue biopsies. 17 To date, most studies have used tissue rebiopsies 13,15,18 or mixed tissue and liquid biopsies 14,19,20 to investigate the clinical factors influencing the incidence of T790M mutation. Only a few studies so far, however, have used liquid biopsies only to investigate this problem.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Acquired EGFR T790M Mutation and EGFR Circulating Cell-Free DNA on Survival in Patients with Lung Adenocarcinoma Following EGFR-TKI Therapy

Cheng

Hsia²,

Tu³

et al. 2021

OTT

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Section: Introductionmentioning

confidence: 99%

The Impact of Acquired EGFR T790M Mutation and EGFR Circulating Cell-Free DNA on Survival in Patients with Lung Adenocarcinoma Following EGFR-TKI Therapy

Cheng

Hsia²,

Tu³

et al. 2021

OTT

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“…As suggested by the authors, resistance acquired after third‐generation EGFR TKIs is associated with different pathways and is not yet understood. In this landscape, the reference range of the CancerSCAN assay is still limited in its ability to elucidate the complexity of third‐generation EGFR TKI resistance mechanisms; a whole‐exome sequencing of serial cfDNA and paired tumor tissue biopsies may represent the best approach to clarify the geographic and evolutionary differences of mutational assets before and after third‐generation EGFR TKI therapy …”

mentioning

confidence: 99%

“…From a biological perspective, the reversion of a mutated allele to a wild‐type allele is a rare occurrence . It is more probable that in the context of a dynamic biological system (such as a solid tumor), the quantity, in terms of variant allele frequency, undergoes drastic changes during treatment until the limit of detection of the technology is unable to detect it . An approach based on the evaluation of serial samples, such as an NGS liquid biopsy–based assay, may help to better define evolutionary selection or deselection of mutated clones during the time .…”

mentioning

confidence: 99%

“…It is more probable that in the context of a dynamic biological system (such as a solid tumor), the quantity, in terms of variant allele frequency, undergoes drastic changes during treatment until the limit of detection of the technology is unable to detect it . An approach based on the evaluation of serial samples, such as an NGS liquid biopsy–based assay, may help to better define evolutionary selection or deselection of mutated clones during the time . Indeed, longitudinal monitoring of mutated alleles during treatment could be very useful in the context of evaluating EGFR TKI resistance mechanisms to assess whether there is a selection or a real emergence of a specific mutation …”

mentioning

confidence: 99%

“…An approach based on the evaluation of serial samples, such as an NGS liquid biopsy–based assay, may help to better define evolutionary selection or deselection of mutated clones during the time . Indeed, longitudinal monitoring of mutated alleles during treatment could be very useful in the context of evaluating EGFR TKI resistance mechanisms to assess whether there is a selection or a real emergence of a specific mutation …”

mentioning

confidence: 99%

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Overcoming resistance to osimertinib in non–small cell lung cancer: Hopes, doubts, and in‐between

Passaro

Malapelle

Attili

et al. 2020

Cancer

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The treatment of non-small cell lung cancer (NSCLC) harboring sensitive EGFR mutations has changed dramatically in the last 15 years, simultaneously improving our clinical and biological knowledge and changing our attitude toward the EGFR-positive disease; furthermore, the use of highly effective tyrosine kinase inhibitors (TKIs) has improved survival, reaching 38.6 months of median overall survival with first-line osimertinib. 1,2 Although such results are significant, resistance to EGFR TKIs inevitably occurs after 10 to 18 months, depending on the TKI compound. 2 To date, efforts to identify the mechanisms of resistance to EGFR TKIs have revealed a predominantly EGFRdependent mechanism in patients receiving first-or second-generation TKIs, who develop the EGFR T790M resistance mutation on exon 20 in 50% to 60% of cases. 3 Treatment with osimertinib significantly improved survival in resistant T790M-positive disease and has recently moved to a front-line setting based on the results of FLAURA trial. 1 Data about osimertinib in both a pretreatment and naïve setting have been encouraging considering its high efficacy and low toxicity. However, despite its promise as a potential new way forward, some clinicians may be hesitant to return to a chemotherapeutic regimen in response to the identification and characterization of resistance alterations rather than clinical trial data.The mechanisms of resistance to third-generation drugs are more heterogeneous, including a higher proportion of EGFR-independent mechanisms compared with EGFR-dependent mechanisms. The "in cis" coexisting C797S point mutation has emerged as the main EGFR-dependent mechanism of resistance to osimertinib across all studies, with a variable rate of incidence. Indeed, among 83 EGFR TKI-pretreated patients expressing a positive EGFR mutation in blood at baseline, C797S mutation was found in 15% of cases at osimertinib resistance in the AURA3 trial 4 and in up to 32% of cases in a pilot trial. 5 Intriguingly, the incidence of C797S resistance mutation is much lower in patients progressing after first-line osimertinib therapy; a recent study by Ramalingam et al 6 showed that among the 91 patients enrolled in the FLAURA study with available pre-and posttreatment blood samples, only 7% developed the C797 mutation. These data are supported by a similar study conducted on patients treated with upfront rociletinib. 7 However, the EGFRindependent mechanisms include a wide and heterogeneous landscape of other receptor tyrosine kinase pathways, such as MET and HER2 amplifications, BRAF and PIK3CA mutations, and gene fusions. 8,9 Presently, the greatest therapeutic progress is focusing precisely on this cluster, highlighting MET as a potential new target for acquired resistance after third-generation EGFR TKIs. 10

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The Implication of Liquid Biopsy in the Non-small Cell Lung Cancer: Potential and Expectation

Ren

Liu

2023

Methods in Molecular Biology

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Clinical Features and Progression Pattern of Acquired T790M-positive Compared With T790M-negative EGFR Mutant Non–small-cell Lung Cancer: Catching Tumor and Clinical Heterogeneity Over Time Through Liquid Biopsy

Cited by 20 publications

References 60 publications

The Impact of Acquired EGFR T790M Mutation and EGFR Circulating Cell-Free DNA on Survival in Patients with Lung Adenocarcinoma Following EGFR-TKI Therapy

The Impact of Acquired EGFR T790M Mutation and EGFR Circulating Cell-Free DNA on Survival in Patients with Lung Adenocarcinoma Following EGFR-TKI Therapy

Overcoming resistance to osimertinib in non–small cell lung cancer: Hopes, doubts, and in‐between

The Implication of Liquid Biopsy in the Non-small Cell Lung Cancer: Potential and Expectation

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