Liquid biopsy data to detect METex14 changes and MET amplification in patients with advanced lung cancer are presented in the AACR

Liquid biopsy by NGS analysis has become a non-invasive alternative in the detection of somatic tumor changes in patients with changes in METex14 and amplification of MET

Work on the biomarker profile of patients screened with liquid biopsy (LBx) was presented at AACR 2020. The VISION phase II and single arm trial (NCT02864992) evaluated tepotinib (a highly selective MET inhibitor) in patients with non-small cell lung cancer (NSCLC) with change in METex14.

Previously confirmed patients with advanced CPNPC and EGFR / ALK were prospectively screened for changes in MET, using plasma samples collected during pre-screening and screening. Plasma sequencing of circulating tumor DNA (ctDNA) was performed in a central laboratory using a 73 gene sequencing panel by NGS (next generation sequencing).

Of the 5,180 patients analyzed, 694 (13.4%) did not have a mutation detected. Despite the intention to screen for wild EGFR / ALK patients, 327 (6.3%) had EGFR mutations and 49 (0.9%) had ALK / ROS fusions. In addition, 188 (3.6%) had changes in METex14 and 256 (4.9%) had MET amplification but without METex14.

The median age of patients with METex14 was 72 years; 47% were male; 46% were never smokers and 65% had histology of adenocarcinoma.

In patients with METex14, the most frequent driver coalterations were amplification in MET (13.3%), EGFR (7.4%), CDK4 (6.4%), BRAF (5.3%) and CDK6 (4.8 %) and mutations in GNAS (5.3%). In patients with MET amplification, the most frequent driver coalterations were CDK6 (60.5%), BRAF (43.4%), EGFR (28.9%), MYC (21.9%) and CCNE1 (19.9 %). Overall, TP53 mutations were detected in 55.9% of patients with METex14 and 79.7% of patients with MET amplification.

In this population of patients with NSCLC altered by METex14, the biomarker can be successfully detected through non-invasive LBx analysis, using an NGS panel. The METex14 rate and the genomic and demographic profile of the patients were similar to the data previously reported.

In summary, it can be said that liquid biopsy by NGS analysis has become a non-invasive

alternative in the detection of somatic tumor changes in patients with changes in METex14 and amplification of MET.

References:

Xiuning Le et al. Liquid biopsy to detect MET exon 14 skipping (METex14) and MET amplification in patients with advanced NSCLC: Biomarker analysis from VISION study. Session MS.CL11.02 – Circulating Tumor DNA for Patient Stratification. Abstract 3385 https://www.abstractsonline.com/pp8/#!/9045/presentation/3826