EGFR T790M mutation testing within the osimertinib AURA Phase I study

Dearden, Simon; Brown, Helen; Jenkins, Suzanne; Thress, Kenneth S.; Cantarini, Mireille; Cole, Rebecca; Ranson, Malcolm R; Jänne, Pasi A.

doi:10.1016/j.lungcan.2017.04.011

Cited by 22 publications

(21 citation statements)

References 30 publications

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“…As with Sanger sequencing, many qPCR kits such as Therascreen (Qiagen) or Cobas (Roche) are validated for “clinical use” in FFPE material. Thus, in theory they are suited for the analysis of liquid biopsies and have been used successfully in clinical studies . By now, liquid biopsy testing by qPCR (Cobas and Therascreen) has been approved by the FDA only for EGFR exon 19 deletions, EGFR L858R and EGFR T790M in NSCLC patients, from whom tissue biopsies cannot be obtained.…”

Section: Different Methods For Mutation Detection In Routine Diagnosticsmentioning

confidence: 99%

“…Thus, in theory they are suited for the analysis of liquid biopsies and have been used successfully in clinical studies. [111][112][113] By now, liquid biopsy testing by qPCR (Cobas and Therascreen) has been approved by the FDA only for EGFR exon 19 deletions, EGFR L858R and EGFR T790M in NSCLC patients, from whom tissue biopsies cannot be obtained. One limitation is that the kits were validated for allele frequencies of >1%.…”

Section: Quantitative Pcrmentioning

confidence: 99%

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A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

Volckmar

Sültmann

Riediger

et al. 2017

Genes Chromosomes & Cancer

165

151

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Recently, many genome-wide profiling studies provided insights into the molecular make-up of major cancer types. The deeper understanding of these genetic alterations and their functional consequences led to the discovery of novel therapeutic opportunities improving clinical management of cancer patients. While tissue-based molecular patient stratification is the gold standard for precision medicine, it has certain limitations: Tissue biopsies are invasive sampling procedures carrying the risk of complications and may not represent the entire tumor due to underlying genetic heterogeneity. In this context, complementary characterization of genetic information in the blood of cancer patients can serve as minimal-invasive 'liquid biopsy'. Fragments of circulating cell-free DNA (cfDNA) are released from tissues of healthy individuals as well as cancer patients. The fraction of cfDNA that is released from primary tumors or metastases (i.e. circulating tumor DNA, ctDNA) represents genetic aberrations in cancer cells, which are a potential source for diagnostic, prognostic, and predictive biomarkers. Recent studies have demonstrated technical feasibility and clinical applications including detection of drug targets and resistance mutations as well as longitudinal monitoring of tumors under therapy. To this end, a variety of pre-analytical procedures for blood processing, isolation and quantification of cfDNA are being employed and several analytical methods and technologies ranging from PCR-based single locus assays to genome-wide approaches are available, which considerably differ in sensitivity, specificity, and throughput. However, broad implementation of ctDNA analysis in daily clinical practice requires a thorough understanding of theoretical, technical, and biological concepts and necessitates standardization and validation of pre-analytical and analytical procedures across different technologies. Here, we review the pertinent literature and discuss the advantages and limitations of available methodologies and their potential applications in molecular diagnostics.

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Section: Different Methods For Mutation Detection In Routine Diagnosticsmentioning

confidence: 99%

Section: Quantitative Pcrmentioning

confidence: 99%

A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

Volckmar

Sültmann

Riediger

et al. 2017

Genes Chromosomes & Cancer

165

151

View full text Add to dashboard Cite

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“…After the failure of first-line treatments, nearly 26.8% of the patients without CNS metastases at entry developed CNS metastases based on the AURA3 and FLAURA trials [4,5]. The frequency of EGFR T790 M mutation, specificities and sensitivities of testing techniques, and successful rebiopsy rate were derived from published studies and are listed in Table 1 [13][14][15][16][17][18]. The probabilities of adverse events for each treatment were obtained from FLAURA and AURA3 trials [4,5].…”

Section: Clinical Inputsmentioning

confidence: 99%

Cost-Effectiveness of Osimertinib in Treating Newly Diagnosed, Advanced EGFR-Mutation-Positive Non-Small Cell Lung Cancer

Wu¹,

Zhang

et al. 2018

The Oncologist

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Background The objective of this study was to assess cost and effectiveness of osimertinib in treating newly diagnosed advanced non‐small cell lung cancer with an epidermal growth factor receptor (EGFR) mutation from a public payer's perspective in the U.S. and China. Materials and Methods Markov models were developed to compare three treatment strategies: first‐line use of osimertinib, first‐line use of the standard first‐generation EGFR‐tyrosine kinase inhibitor (EGFR‐TKI) followed by the second‐line use of osimertinib, and the standard first‐generation EGFR‐TKI therapy (standard care [SOC]). Clinical data, cost, and utility data were mainly derived from published literatures. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the incremental cost per quality‐adjusted life year (QALY) between the treatments. Results The resultant incremental cost per QALY gained for the first‐line osimertinib versus SOC was $312,903 in the U.S. and $41,512 in China. The incremental cost per QALY for the second‐line osimertinib versus SOC was $284,532 in the U.S. and $38,860 in China. The probability of the SOC strategy being cost‐effective is 1.0 if the willingness to pay threshold is below $150,000/QALY in the U.S. and below $30,000/QALY in China. Conclusion Osimertinib as first‐line treatment could gain more health benefits in comparison with standard EGFR‐TKIs or second‐line use of osimertinib. However, because of the high cost of treatment, the cost‐effectiveness analyses were not in favor of the first‐line use of osimertinib from a public payer's perspective in the U.S. and China. Implications for Practice Osimertinib as first‐line treatment yielded the greatest health outcomes but is not a cost‐effective strategy for lung cancer in the U.S. and China. The price of osimertinib has a substantial impact on economic outcomes.

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“…The ASSESS trial in Europe and Japan (NCT01785888, designed for real-world diagnostic validation of Therascreen EGFR PCR Kit (Qiagen), cobas EGFR Mutation Test (Roche), Cycleave (Takara Bio Inc., Kusatsu, Japan) and PNA-LNA PCR Clamp kits (Qiagen), for testing EGFR mutation found identical sensitivity when both plasma and tissue was tested using the same commercial kit [52]. Phase I expansion component of the AURA Phase I/II study (NCT01802632) conducted in USA and Japan, also, validated the use of various EGFR testing methodologies including cobas® EGFR Mutation Test, Sanger sequencing, Therascreen®, PNAClamp™, and Sequenom MassARRAY® [53].…”

Section: Methods Targeting Druggable Mutation and Other Aberrations Imentioning

confidence: 87%

Liquid biopsy - emergence of a new era in personalized cancer care

2018

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The most successful treatment for cancer involves identifying druggable, biological markers for targeted therapy. In the clinical setting, surgical removal of tumors is the only procedure for identifying such targetable molecules. Shed from tumor cells, these markers are also present in circulating blood, albeit in very negligible amounts. Liquid biopsy is a procedure performed on a blood sample to look for such circulating cancer markers cells or pieces of nucleic acid from the tumor. The procedure shows promise in revolutionizing personalized cancer treatments. Here we briefly review the technique, characterization, and its utilization in clinics.

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EGFR T790M mutation testing within the osimertinib AURA Phase I study

Cited by 22 publications

References 30 publications

A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

Cost-Effectiveness of Osimertinib in Treating Newly Diagnosed, Advanced EGFR-Mutation-Positive Non-Small Cell Lung Cancer

Liquid biopsy - emergence of a new era in personalized cancer care

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