Abstract 21P
Background
MET amplification is one of acquired resistance mechanism to EGFR-TKIs in EGFRm advanced NSCLC patients(pts). However, comprehensive data using NGS and FISH for detecting MET amplification is limited in Chinese patients.
Methods
Patients progressed after 1st-, 2nd-, or 3rd-generation EGFR-TKIs were enrolled. Tissue biopsy samples were performed for MET amplification detection via both NGS and FISH. Paired plasma samples were also collected for MET amplification detection by NGS. The sensitivity, specificity and agreement were analyzed between NGS and FISH.
Results
116 post EGFR-TKI resistant pts were analyzed. 45(38.8%) pts were male. 34(29.3%) pts were after 1st or 2nd generation EGFR-TKI, 80(69.0%) pts after 3rd generation EGFR-TKI, while 2(1.7%) pts with lack of data on specific EGFR-TKI drug or combined 1st and 3rd EGFR-TKI. MET amplification was detected in 43(37.1%) patients by FISH, including 19(16.4%) with polysomy and 24(20.7%) with focal amplification. The positive rate of MET amplification in post 3rd gen EGFR-TKI and post 1st/2nd gen EGFR-TKI resistant pts was 45.0% (36/80) and 20.6% (7/34), respectively. Using FISH as reference, the sensitivity, specificity and agreement of detecting MET amplification by NGS in tissue were 39.5%(17/43), 98.6% (72/73) and 76.7% (89/116), respectively. For focal MET amplification in tissue, the sensitivity, specificity and agreement were 66.7%(16/24), 98.6% (72/73) and 90.7%(88/97), respectively. For focal MET amplification in plasma, the sensitivity, specificity and agreement were 29.2%(7/24), 94.5%(69/73) and 78.4%(76/97). Results were both shown in the table.
Table: 21P
Performance of NGS in tissue and plasma
| NGS testing | Sensitivity | Specificity | Agreement | |
| Tissue | Total | 39.5% | 98.6% | 76.7% |
| Focal amplification | 66.7% | 98.6% | 90.7% | |
| Plasma | Total | 20.9% | 94.5% | 67.2% |
| Focal amplification | 29.2% | 94.5% | 78.4% |
Conclusions
NGS is an alternative method for MET focal amplification detection in tissue. While the sensitivity of NGS testing in plasma needs further improvement to maximize identification of pts with potential benefit from dual-targeted therapy.
Legal entity responsible for the study
Department of Pulmonary and Critical Care Medicine, West China Hospital.
Funding
AstraZeneca.
Disclosure
The author has declared no conflicts of interest.