EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AZD9291

Thress, Kenneth S.; Brant, Roz; Carr, T. Hedley; Dearden, Simon; Jenkins, Suzanne; Brown, Helen; Hammett, Tracey; Cantarini, Mireille; Barrett, J. Carl

doi:10.1016/j.lungcan.2015.10.004

Cited by 449 publications

(396 citation statements)

References 27 publications

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“…Interestingly, 18/164 patients with plasma T790M-positive genotyping were T790M-negative on tissue analysis, showing favorable clinical outcomes similar to those of patients with T790M-positive tumor tissue (Oxnard et al, 2016). These data, consistently with those observed in other studies evaluating plasma genotyping approach at the time of PD (Takahama et al, 2016;Thress et al, 2015), demonstrated a lower specificity of plasma-based detection of T790M at PD compared to EGFR-activating mutations detection at baseline, likely due to the higher heterogeneity of TKI-resistant tumors. As single tissue biopsy is just a snapshot of the tumor not reflecting its spatial heterogeneity, ctDNA could be more representative of the overall tumor mutation status, allowing to identify different targetable alterations driving tumor resistance.…”

Section: Potential Application At Progressionsupporting

confidence: 82%

EGFR inhibition in NSCLC: New findings…. and opened questions?

Passiglia

Listì

Castiglia

et al. 2017

Critical Reviews in Oncology/Hematology

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The targeted inhibition of epidermal growth factor receptor (EGFR) has represented a milestone in the treatment of lung cancer. Several studies convincingly and consistently demonstrated a significant superiority of EGFR-TKIs over standard platinum-chemotherapy in EGFR-mutated NSCLC patients, leading to the sequential approval of gefitinib, erlotinib and afatinib as new standard first-line clinical treatment. To date we are witnessing a second revolution in the management of EGFR-positive NSCLC thanks to the development of new treatment strategies aiming to overcome acquired resistance to TKIs and ultimately improve patients’ outcomes. In this review we summarize the most important recent findings regarding EGFR-inhibition in NSCLC, highlighting the current unsolved questions on the selection of the best TKI in first-line, which therapy can be combined with upfront EGFR-TKIs, how to overcome acquired resistance, and which are the clinical applications of liquid biopsy

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Section: Potential Application At Progressionsupporting

confidence: 82%

EGFR inhibition in NSCLC: New findings…. and opened questions?

Passiglia

Listì

Castiglia

et al. 2017

Critical Reviews in Oncology/Hematology

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“…Using BEAMing digital PCR analysis, Oxnard et al found that the sensitivity of plasma genotyping for detection T790M was 70% (17), comparable that reported previously (21). T790M mutation was detected in 18 of 58 (31%) patients with T790M negative tumor.…”

Section: Commentarysupporting

confidence: 67%

Harnessing plasma genotyping for precision therapy against lung cancer

Yan

Fang

2016

J. Thorac. Dis.

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“…Numerous studies have yielded evidence that ctDNA can be used to complement tumor DNA testing to detect these genetic alterations. Thress et al demonstrated the efficacy of two different platforms to detect T790M in blood, with a sensitivity of 73% and 81% and specificity of 67% and 58% (40). In one study, similar objective response rates (ORR) were seen in patients treated with rociletinib, regardless of whether T790M was detected in tumor or plasma (21).…”

Section: Role Of Ctdna In the Resistance Settingmentioning

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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EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AZD9291

Cited by 449 publications

References 27 publications

EGFR inhibition in NSCLC: New findings…. and opened questions?

EGFR inhibition in NSCLC: New findings…. and opened questions?

Harnessing plasma genotyping for precision therapy against lung cancer

Circulating DNA in EGFR-mutated lung cancer

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