CSIG-06 - Retrospective review of glioma patients with confirmed MET amplification or fusion

Friday, November 18, 2022

7:30 PM – 9:30 PM ET

Location: West/Central Hall

Poster Presenter(s)

Ramya Tadipatri, MD

Flagstaff Medical Center
Phoenix, United States

Author(s)

Chukwuyem Ekhator, OMS-III MBBS MPH (he/him/his)

College of Osteopathic Medicine, New York Institute of Technology
Old Westbury, United States
AM

Adela Miller, MD

Barrow Neurological Institute
Phoenix, United States
JG

Jai Grewal, MD

Mount Sinai South Nassau Hospital, Oceanside, NY
Oceanside, United States
Manmeet S. Ahluwalia, MD, MBA

Miami Cancer Institute, Baptist Health South Florida
Miami, United States
Ekokobe Fonkem, DO

Baylor Scott & White Temple
Temple , United States

Background: The MET pathway is a key oncogenic pathway in gliomas and is involved in tumor survival, angiogenesis, and invasion. MET alterations have been increasingly identified as a potential therapeutic target.

Methods: Our objective was to further characterize the natural history of gliomas which harbor MET alterations and study outcomes as determined by progression free survival (PFS) and overall survival (OS).

Results: We identified 22 glioma patients seen at our institution between 2015 and 2021 who had a MET alteration confirmed through comprehensive molecular profiling. There were 18 grade 4 astrocytomas/glioblastomas, 3 grade 3 gliomas (2 astrocytomas, 1 oligodendroglioma), and 1 grade 2 glioma (oligodendroglioma). MET amplification was observed in 13 patients and fusion in 16 patients , with 7 patients carrying both amplification and fusion alterations. MET fusion partners included PTPRZ1 (8 patients), CAPZA2 (6 patients), and ST7 (3 patients). Median OS was 12.8 months, and median PFS was 8.47 months. IDH1/2 mutation was associated with significantly improved survival, with an estimated OS of 146 months for IDH1/2 mutant tumors and 17.9 months for IDH1/2 wildtype tumors (p < 0.001), MGMT methylation status had no significant survival impact. No significant survival differences were observed between the fusion only, amplification only, and combined fusion and amplification groups. No therapy was predictive of improved outcomes.

Conclusion: MET amplification and fusion alterations were observed in both low and high grade gliomas, suggesting that they may be involved in early tumorigenesis. Survival outcomes were poor compared with historical data, with no differences observed between treatment groups, suggesting that current therapeutic modalities may be inadequate. This study indicates that MET may be an appropriate therapeutic target, laying the groundwork for clinical trials investigating MET-targeted agents.