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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

5528 - Comparison of Tissue-Based and Liquid Biopsy Genomic Tests to Guide Lung Cancer Therapy – Asian Experience

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Maarja-Liisa Nairismägi

Citation

Annals of Oncology (2018) 29 (suppl_8): viii479-viii482. 10.1093/annonc/mdy294

Authors

M. Nairismägi1, K. Tung2, Y. Yang2, Y. Lu2, R. Jhou2, P. Yu2, Y. Liu2, Y. Hsieh2, S.L. Poon3, S. Chen2, K.T. Tan2

Author affiliations

  • 1 Medical Affairs, ACT Genomics (Singapore) Pte. Ltd., 138623 - Singapore/SG
  • 2 Medical Informatics, ACT Genomics Co., Ltd., Taipei/TW
  • 3 Medical Affairs, ACT Genomics (Singapore) Pte. Ltd., Singapore/SG
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Resources

Abstract 5528

Background

Liquid biopsies are rapidly changing the diagnostics in oncology; however, their usability to guide treatment selection remains unknown. Here we explored the differences between liquid biopsy and tissue-based genomic tests in Asian lung cancer patients.

Methods

226 formalin-fixed, paraffin-embedded (FFPE) and 274 plasma clinical samples were subjected to next-generation sequencing using the Ion Torrent Proton System with mean sequencing depth ≥700× and 7,000×, respectively. FFPE samples were profiled using a 35-gene and circulating tumor DNA samples a 11-gene hotspot panel for base substitutions (single nucleotide variants/small indels) and copy number variants (CNV; for FFPE only).

Results

Actionable variants were identified in 47% (129/274) of liquid biopsies. Actionability was higher in tissue-based tests – 76% (172/226) – with 64% (111/172) derived from base substitutions, 9% (15/172) from CNVs and 27% (46/172) from both. EGFR mutations, indicating the use of tyrosine kinase inhibitors (TKI), were detected in 38% (105/274) and 49% (110/226) of liquid biopsy and tissue-based tests, respectively. Identification of TKI resistance mechanisms via EGFR T790M/C797S or the downstream KRAS, BRAF, PIK3CA, ERBB2 and MET mutations was also higher for tissue testing – alterations were discovered in 38% (86/226) and 27% (75/274) of samples, affecting a total of 35% (78/226) and 24% (65/274) patients, respectively, for tissue and liquid biopsy tests. Tissue testing detected additional CNV-originating TKI resistance mechanisms (EGFR, MET and HER2 amplifications) in 24% (53/226) samples affecting an additional 13% (30/226) patients on top of those harboring mutation-based resistance mechanisms. RAF and MEK inhibitor indications were identified in 12% (28/226) and 3% (8/274), and mTOR blockade indications in 8% (19/226) and 7% (19/274) of tissue and liquid biopsy tests, respectively.

Conclusions

Although liquid biopsy tests are able to identity a large proportion of lung cancer patients with indications for targeted therapy, tissue-based testing outperforms liquid biopsies for most therapeutic indications. Inclusion of CNV analysis could potentially increase the detection rate in liquid biopsies.

Clinical trial identification

Legal entity responsible for the study

ACT Genomics Co., Ltd.

Funding

ACT Genomics Co., Ltd.

Editorial Acknowledgement

Disclosure

M-L. Nairismägi, K-C. Tung, Y-T. Yang, Y-J. Lu, R-S. Jhou, P-N. Yu, Y-T. Liu, Y-L. Hsieh, S.L. Poon, K.T. Tan: Employee: ACT Genomics. S-J. Chen: Employee and shareholder: ACT Genomics.

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