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Efficacy of tepotinib in patients with high-grade glioma with MET alterations: A case series

Year: 2025

Type: article

Abstract: Background Glioblastoma is the most common and aggressive adult brain malignancy, characterized by poor prognosis and limited treatment options. The MET (hepatocyte growth factor receptor) oncogene plays a crucial role in tumor progression, with alterations such as gene amplification and fusion events contributing to worsened prognosis, decreased survival rates, and resistance to standard chemotherapy treatments. Case Summary This case series documents the clinical outcomes of 5 patients with MET-altered glioblastoma treated with tepotinib, a highly selective MET tyrosine kinase inhibitor approved for patients with MET exon 14 skipping advanced/metastatic non-small cell lung cancer, in routine clinical practice in the United States. The patients received tepotinib through ad hoc off-label requests, with a daily dosage of 450 mg after progression following radiotherapy-based first-line treatment, with or without temozolomide. The efficacy and safety outcomes were assessed based on physicians’ evaluations. Tepotinib demonstrated clinical benefit, with partial response observed in 2 patients, stable disease in 2 patients, and progressive disease in 1 patient. The duration of tepotinib treatment ranged from 0.7 to >15 months, with treatment ongoing in 1 patient as of June 2025. Adverse events were generally mild to moderate, including grade 2 peripheral edema, grade 1 increased alanine aminotransferase levels, and grade 2 elevated liver function tests. Conclusions These findings support the potential of tepotinib as a targeted therapy for MET-altered glioblastoma, consistent with preclinical evidence and previous case reports. Further research is warranted to better understand the efficacy and safety of MET inhibition in this patient population.

Source: Neuro-Oncology Practice

DOI: 10.1093/nop/npaf130

Authors: Andrew Rodriguez, Karan Dixit, Richard M O’Hara, Morana Vojnic

Institutions: University of Kansas Medical Center, Northwestern University, EMD Serono, Inc. (United States), Rutgers Cancer Institute

Language: English

Topic: Glioma Diagnosis and Treatment

Subfield: Genetics

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $5,036