Comparison of OncoBEAM and NGS methods to detect plasma EGFR T790M mutations at progression of NSCLC

Date 20 October 2018
Event ESMO 2018 Congress
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
Topics Personalised/Precision Medicine
Pathology/Molecular Biology
Presenter Jessica Garcia
Citation Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269
Authors J. Garcia1, A. Delherme1, F. Geigeur1, P. Merle2, C. Tissot3, F.S. Jones4, D. Edelstein5, P. Souquet6, C. Rodriguez-Lafrasse1, S. Couraud6, L.F. PAYEN1, Z. Xu7
  • 1Biochemistry And Molecular Biology Department Of Lyon Sud, Hospices Civiles de Lyon, 69002 - Lyon/FR
  • 2Oncology, Centre Jean Perrin, 63011 - Clermont-Ferrand/FR
  • 3Oncology, CHU de Saint Etienne, Hôpital du Nord, 42277 - St. Priest en Jarez/FR
  • 4Oncology, Sysmex-Inostics, Inc., New York/US
  • 5Oncology, Sysmex Inostics, Baltimore/US
  • 6Oncology, Centre Hospitalier Lyon Sud, 69495 - Pierre Bénite/FR
  • 7Bio-informatics, Sophia-genetics, 01 - lausanne/CH

Abstract

Background

Various methods have been employed to detect plasma EGFR mutations in patients with non-small cell lung cancer patients (NSCLC). Therefore, we evaluated the performance of digital PCR and next generation sequencing (NGS) to detect the p.T790M EGFR mutation in prospectively collected patient samples. Paired plasma samples from patients (CIRCAN cohort) that progressed on first-line EGFR TKI therapy were compared using two platforms: OncoBEAMTM-EGFR (Sysmex Inostics) and NGS (Illumina), utilizing the 56G oncology panel (Swift Biosciences).

Methods

196 stage 4 NSCLC patients with EGFR alteration under TKI were included from various center. Blood was collected in a routine setting, when physician noted changes in CT scans that were suspicious of progression. CfDNA analysis is recommended in front line in this setting in France. Replicate plasma samples were analysed using OncoBEAM and NGS. The thresholds for calling EGFR plasma mutations were 0.5% and 0.02% for NGS and OncoBEAM, respectively and were validated using cfDNA reference standards (Horizon Discovery).

Results

OncoBEAM detected the p.T790M mutation in 36/196 patients (18.3%), whereas NGS detected T790M in 20/196 patients (10.2%). The agreement of NGS vs OncoBEAM for T790M detection was 55.6%. The p.T790M-positive samples detected by OncoBEAM but missed by NGS were all found to have low mutant allelic fractions (under 0.35%). With regard to sensitizing EGFR mutations, 28/36 OncoBEAM T790M+ patients had accompanying EGFR mutations, whereas all 20/20 NGS T790M+ samples showed presence of sensitizing mutations. In contrast to OncoBEAM, NGS testing revealed other somatic alterations including ERBB2 amplification, and mutations in TP53.

Conclusions

In conclusion, these findings highlight the value of OncoBEAMTM-EGFR and NGS for detecting T790M at early progression. While less sensitive, NGS provided broader genomic coverage which may reveal diverse mechanisms of resistance. In contrast, OncoBEAM delivers superior sensitivity for focused detection of known resistance alterations such as EGFR T790M. Thus, OncoBEAM may provide the sensitivity required to monitor the kinetics of circulating tumor DNA and correlations with therapeutic response.

Clinical trial identification

Legal entity responsible for the study

Hospices Civils of Lyon.

Funding

Sysmex Innostics / AstraZeneca.

Editorial Acknowledgement

Disclosure

C. Tissot, P-J. Souquet: Membership on pharma advisory board. F.S. Jones, D. Edelstein: Sysmex Innostics. S. Couraud: AstraZeneca, Roche, MSD, Novartis, BMS, Boehringher Ingelheim, Chugai, Pfizer, Lilly, Merck. L.F. Payen: Membership on BMS; Advisory board: AstraZeneca. Z. Xu: Sophia Genetics. All other authors have declared no conflicts of interest.