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Poster display session

4750 - EGFR Mutation Detection in Plasma Cell-free DNA Correlates with Clinical Outcomes in Non-Small Cell Lung Cancer

Date

09 Sep 2017

Session

Poster display session

Topics

Cancers in Adolescents and Young Adults (AYA);  Translational Research;  Non-Small Cell Lung Cancer

Presenters

Junli Shi

Citation

Annals of Oncology (2017) 28 (suppl_5): v460-v496. 10.1093/annonc/mdx380

Authors

J. Shi1, J. Mong1, T.M. Chin2, Y.H. Lim1, W.L. Tan3, C.K. Toh3, H.S. Tan3, S. Wong4, A. Tee5, D. Chan6, K. Wong6, S. Yeap7, L. Ngo8, Y. Tan6, M. Tan1

Author affiliations

  • 1 Biodevices And Diagnostics, Insitute of Bioengineering and Nanotechnology (IBN), 138669 - Singapore/SG
  • 2 National University Cancer Institute, National University Cancer Institute, Singapore/SG
  • 3 Division Of Medical Oncology, National Cancer Centre, Singapore/SG
  • 4 The Cancer Centre, The Cancer Centre, 238859 - Singapore/SG
  • 5 Department Of Respiratory & Critical Care Medicine, Changi General Hospital, 529889 - Singapore/SG
  • 6 Singapore Oncology Consultants, Singapore Oncology Consultants, 228510 - Singapore/SG
  • 7 Novena Cancer Centre, Novena Cancer Center-Mount Elizabeth Specialist Centre, 329563 - Singapore/SG
  • 8 Raffles Cancer Centre, Raffles Hospital, 188770 - Singapore/SG
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Resources

Abstract 4750

Background

Cell-free DNA (cfDNA) testing of epidermal growth factor receptor mutations (EGFRmut) is being investigated as an adjunct for diagnosis and monitoring in non-small cell lung cancer (NSCLC) patients. The performance of various amplicon-based targeted next-generation sequencing (NGS) methods, both with and without error correction, is of high interest. Outcomes of error-corrected NGS in plasma EGFRmut testing have not been previously independently reported. We deployed an in-house amplification-refractory mutation system PCR (ARMS-PCR) assay in a prospective study, benchmarking its performance against two NGS platforms in a patient subset.

Methods

An ultrasensitive ARMS-PCR assay for hotspot EGFRmut was established, with detection limits between 0.02% and 0.1%. A total of 134 plasma samples were prospectively analysed from 68 patients with metastatic lung adenocarcinoma at diagnosis or progression, recruited between Jan 13-Apr 17 from 5 centres, with serial monitoring of plasma EGFRmut till radiologic progression in one centre. We further evaluated the performance of ARMS-qPCR assay, AmpliSeq Lung and Colon NGS assay and Oncomine Lung cfDNA NGS assay in 29 NSCLC and 20 healthy plasma controls.

Results

Concordance rate between cfDNA and tumor was 83.8%, with sensitivity 80.0%, specificity 94.4%, positive predictive value 97.6%, and negative predictive value 63.0%. Dynamic monitoring of plasma EGFRmut levels demonstrated rising levels a median of 2.1 months [0.9-3.9] before radiological progression. This detection also held true for tissue EGFRmut positive patients negative for plasma EGFRmut at study entry. 20 of 49 patients at progression were plasma T790M-positive, and clinical benefit rates were 91.0% for osimertinib-treated patients. Evaluation of ARMS-PCR and NGS platforms yielded an average concordance rate, sensitivity and specificity was 85.9%, 63.4%, 92.3% (ARMS-qPCR), 87.2%, 47.8%, 100% (Ampliseq) and 84.1%, 83.1%, 87.4% (Oncomine).

Conclusions

ARMS-PCR provides a useful diagnostic and monitoring adjunct for NSCLC EGFRmut patients. Amplicon-based targeted next-generation sequencing approaches with error correction is a promising approach requiring additional validation.

Clinical trial identification

Legal entity responsible for the study

Institute of Bioengineering and Nanotechnology

Funding

Agency for Science, Technology and Research (A*STAR)

Disclosure

All authors have declared no conflicts of interest.

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