Dynamic Plasma EGFR Mutation Status as a Predictor of EGFR-TKI Efficacy in Patients with EGFR-Mutant Lung Adenocarcinoma

Tseng, Jeng‐Sen; Yang, Tsung‐Ying; Tsai, Chi-Ren; Chen, Kun‐Chieh; Hsu, Kuo-Hsuan; Tsai, Meen-Hsin; Yu, Sung-Liang; Su, Kang‐Yi; Chen, Jeremy J.W.; Chang, Gee‐Chen

doi:10.1097/jto.0000000000000443

Cited by 61 publications

(49 citation statements)

References 34 publications

(19 reference statements)

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“…Our previous study has demonstrated that plasma EGFR mutation status can be dynamically assessed and also serve as an independent outcome predictor of EGFR-TKI therapy [33]. Theoretically, this concept can also be applied in both T790M detection and third generation EGFR-TKI therapy.…”

Section: Discussionmentioning

confidence: 99%

The emergence of T790M mutation in EGFR-mutant lung adenocarcinoma patients having a history of acquired resistance to EGFR-TKI: focus on rebiopsy timing and long-term existence of T790M

Tseng

Yang

et al. 2016

Oncotarget

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Different growth kinetics occurring between the sensitive and T790M-containing cells may result in the repopulation of tumor cells over time. Little information has yet been uncovered on whether rebiopsy timing influences the T790M detection rate. We enrolled a total of 98 epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients, who had a history of acquired resistance to EGFR-tyrosine kinase inhibitor (TKI) and available rebiopsy tumor specimens for reassessment of EGFR mutations. Rebiopsy was performed at the time of first EGFR-TKI progression in 54 patients (55.1%); for the other 44 patients (44.9%), rebiopsy was done with an interval from first EGFR-TKI progression (median 470.5 days, range 46-1742 days). Our results indicated that rebiopsy timing did not influence the detection rate of T790M and that the mutation could be identified in patients with a long EGFR-TKI-free interval. For patients without suitable lesions for rebiopsy at the time of EGFR-TKI progression, an attempt to rebiopsy should be considered during the subsequent treatment courses.

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Section: Discussionmentioning

confidence: 99%

The emergence of T790M mutation in EGFR-mutant lung adenocarcinoma patients having a history of acquired resistance to EGFR-TKI: focus on rebiopsy timing and long-term existence of T790M

Tseng

Yang

et al. 2016

Oncotarget

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“…Another study in 72 patients with advanced non-small cell lung cancer examined the dynamic changes in cfDNA EGFR mutations as a predictor of response to EGFR tyrosine-kinase inhibitor (EGFR-TKI) targeted therapy [101]. Failure to clear plasma EGFR mutations after EGFR-TKI was an independent predictor for shorter PFS (hazard ratio [HR] 1.97, P = 0.001) and OS (HR 1.82, P = 0.036).…”

Section: Clinical Application Of Cfdna In Cancer Managementmentioning

confidence: 99%

Testing for oncogenic molecular aberrations in cell-free DNA-based liquid biopsies in the clinic: are we there yet?

Polívka

Pešta

Janků

2015

Expert Review of Molecular Diagnostics

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Summary The optimal choice of cancer therapy depends upon analysis of the tumor genome for druggable molecular alterations. The spatial and temporal intratumor heterogeneity of cancers creates substantial challenges, as molecular profile depends on time and site of tumor tissue collection. To capture the entire molecular profile, multiple biopsies from primary and metastatic sites at different time points would be required, which is not feasible for ethical or economic reasons. Molecular analysis of circulating cell-free DNA offers a novel, minimally invasive method that can be performed at multiple time-points and plausibly better represents the prevailing molecular profile of the cancer. Molecular analysis of this cell-free DNA offers multiple clinically useful applications, such as identification of molecular targets for cancer therapy, monitoring of tumor molecular profile in real time, detection of emerging molecular aberrations associated with resistance to particular therapy, determination of cancer prognosis and diagnosis of cancer recurrence or progression.

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“…A prospective analysis of advanced NSCLC patients demonstrated that patients with complete resolution of ctDNA at either 2 or 6 weeks after treatment, exhibited a lower treatment discontinuation rate (0% at initial and 4% at second reimaging) compared to patients without complete resolution (33% at initial and 56% at second reimaging), presumably correlating with radiographic response and emergence of acquired resistance (11). Another prospective study followed 62 EGFR mutant NSCLC patients receiving TKI therapy with serial plasma ctDNA testing (56 (57). All 40 patients with EGFR mutations at baseline showed a significant reduction of mutant copies (>50%) in plasma during the first 2 months after treatment.…”

Section: Role In Longitudinal Clinical Monitoringmentioning

confidence: 99%

Circulating DNA in EGFR-mutated lung cancer

Singh¹,

Li²,

Cheng³

2017

Ann. Transl. Med.

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Circulating tumor DNA (ctDNA) consists of short double stranded DNA fragments that are released by tumors including non-small cell lung cancer (NSCLC). With the identification of driver mutations in the epidermal growth factor receptor (EGFR) gene and development of targeted tyrosine kinase inhibitors (TKIs), the clinical outcome of NSCLC patients in this subgroup has improved tremendously.The gold standard to assess EGFR mutation is through tissue biopsy, which can be limited by difficulty in accessing the tumor, inability of patients to tolerate invasive procedures, insufficient sample for molecular testing and inability to capture intratumoral heterogeneity. The great need for rapid and accurate identification of activating EGFR mutations in NSCLC patients paves the road for ctDNA technology.Studies have demonstrated ctDNA to be a reliable complement to tumor genotyping. Platforms like digital polymerase chain reaction (PCR) and next-generation sequencing based analyses have made it possible to identify EGFR mutations in plasma with high sensitivity and specificity. This article will provide an overview on ctDNA in the context of EGFR mutated NSCLC, especially its emerging applications in diagnosis, disease surveillance, treatment monitoring and detection of resistance mechanisms.

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Dynamic Plasma EGFR Mutation Status as a Predictor of EGFR-TKI Efficacy in Patients with EGFR-Mutant Lung Adenocarcinoma

Abstract: Changes in plasma EGFR mutation status can be successfully assessed using the peptide nucleic acid-zip nucleic acid polymerase chain reaction clamp method and can serve as an independent outcome predictor.

Cited by 61 publications

References 34 publications

The emergence of T790M mutation in EGFR-mutant lung adenocarcinoma patients having a history of acquired resistance to EGFR-TKI: focus on rebiopsy timing and long-term existence of T790M

The emergence of T790M mutation in EGFR-mutant lung adenocarcinoma patients having a history of acquired resistance to EGFR-TKI: focus on rebiopsy timing and long-term existence of T790M

Testing for oncogenic molecular aberrations in cell-free DNA-based liquid biopsies in the clinic: are we there yet?

Circulating DNA in EGFR-mutated lung cancer

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