Prevalence of MET aberration using next generation sequencing in oncology clinic: A real-world experience.

e16099 Background: MET has been known as an important therapeutic target in various solid cancer types. With the establishment of next-generation sequencing (NGS) in the oncology clinics, understanding the incidence of MET aberration in patients with metastatic cancer is critical for oncology drug development and efficacy. We investigated MET gene aberration in 2,239 oncology patients who underwent NGS in clinical practice with real-world data. Methods: From Nov. 2019 to Jan. 2021, 2,239 metastatic solid tumor patients who visited oncology clinic were enrolled in the NGS analysis. The NGS panel (TruSight Oncology 500 Assay, Illumina) was over 500 comprehensive sequencing using archival tissue specimen. In addition, PD-L1 22C3 assay results were available in 1,137 patients (50.8%) and 1,761(78.7%) patients had clinical record about 1st chemotherapy for overall survival analysis. Results: 2,239 patients with metastatic solid tumor (37 cancer types) received NGS as part of the clinical practice with an aim to be guided to targeted agents or immunotherapy. The most common cancer types were CRC (N = 702, 31.4%), followed by GC (N = 481, 21.5%), and sarcoma (N = 180, 8.0%). Of 2,239 patients, any MET aberrations (CNVs, fusions, and SNV) were detected in 212 patients. Of the 46 patients with MET amplification, 14 (30.4%) were GC followed by CRC (N = 10, 21.7%), melanoma (N = 7, 15.2%), CCC (N = 6, 13.0%), sarcoma (N = 2, 4.3%), HCC (N = 2, 4.3%), NSCLC (N = 2, 4.3%), pancreatic cancer (N = 2, 4.3%), and gallbladder cancer (N = 1, 2.2%). All MET-amplified tumors had microsatellite stable (MSS) status and 17.4 % patients (N = 8) were TMB-high status. And, 8 of MET-amplified patients concurrently showed MET-positive protein expression by IHC (2+ and 3+). Of note, MET fusion was detected in 0.4% (10 of 2,239) of the patients. The partner gene included ST7, TFEC, LRRD1, CFTR, CAV1, PCM1, HLA-DRB1 and CAPZA2. In survival analysis, patients having MET amplification or fusion had shorter OS and PFS than the others, suggesting MET aberration was an important key factor that could determine final response results to current chemotherapy. Conclusions: Based on our comprehensive NGS survey focused on MET aberration, we identified approximately 2.1% MET amplification and 0.4% MET fusion in patients with metastatic solid tumors. They showed worse response after chemotherapy and shorter OS and PFS.