Abstract 677P
Background
MET amplification (amp) is a key resistance mechanism in EGFR mutant (EGFRm) advanced NSCLC patients (pts) post first-line (1L) osimertinib (osi) failure. Fluorescence in situ hybridization (FISH) is golden standard for MET amp detection, while next-generation sequencing (NGS) was widely used in clinical practice. Droplet digital polymerase chain reaction (ddPCR) was also an alternative method for MET amp detection in plasma. The concordance of NGS and ddPCR vs FISH for MET amp detection in these pts needs to be validated.
Methods
EGFRm NSCLC pts post 1L osi progression were prospectively enrolled with paired tissue and blood. MET amp was tested by FISH and NGS in tissue and by ddPCR and NGS in plasma. Tissue NGS assay was optimized in this study with new MET gene copy number (GCN) cut-off of 8.63. Taking MET GCN≥10 by FISH as high level MET amp positive based on the SAVANNAH study, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MET amp detection was analyzed in NGS (tissue and plasma), optimized NGS (tissue), and ddPCR (plasma) vs FISH.
Results
Thirty-six pts were tested MET amp by FISH, NGS and ddPCR. The prevalence of MET amp by FISH (GCN≥10) was 13.9%. The concordance in different platforms was shown in the table. In tissue, optimized NGS showed improved specificity (71.0% vs 100%) and accuracy (75.0% vs 100%) compared to NGS with non-optimized, maintaining high sensitivity 100%. In plasma, ddPCR presented higher sensitivity (100% vs 40.0%) and accuracy (94.4% vs 88.9%) with similar specificity (93.6% vs 96.8%) Table: 677P
Concordance of MET amp
| Sample | Methods (vs FISH) | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) | Accuracy (%) |
| Tissue | Non-optimized NGS | 100 | 71.0 | 35.7 | 100 | 75.0 |
| Optimized NGS | 100 | 100 | 100 | 100 | 100 | |
| Plasma | NGS | 40.0 | 96.8 | 66.7 | 90.9 | 88.9 |
| ddPCR | 100 | 93.6 | 71.4 | 100 | 94.4 |
Conclusions
In tissue, optimized NGS is an acceptable method for MET amp detection in EGFRm advanced NSCLC pts post osi 1L failure. Plasma is an alternative sample for MET amp testing when tissue is unavailable. Further validation is needed by studies with larger sample size.
Clinical trial identification
NCT05219162.
Editorial acknowledgement
Medical writing and editorial support were provided by Hangzhou Tigermed Consulting Co., Ltd.
Legal entity responsible for the study
AstraZeneca China.
Funding
AstraZeneca China.
Disclosure
All authors have declared no conflicts of interest.