Tepotinib for treating advanced non-small-cell lung cancer

Tepotinib is a once-daily, highly selective oral MET inhibitor

• trial evidence showed that patients with advanced non-small-cell lung cancer (NSCLC) with a confirmed MET exon 14 skipping mutation, the use of tepotinib was associated with a partial response in approximately half the patients (1)
  • peripheral edema was the main toxic effect of grade 3 or higher

NICE state (2):

• tepotinib is recommended, within its marketing authorisation, as an option for treating advanced non-small-cell lung cancer (NSCLC) with METex14 skipping alterations in adults, only if the company provides tepotinib according to the commercial agreement

Notes:

• MET and NSCLC
  • a splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver MET
    • occurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC)
      • MET dysregulation through splice-site alterations that cause a loss of transcription of exon 14 in MET can result from point mutations, insertions or deletions, or large-scale whole-exon deletions
      • MET proto-oncogene encodes a receptor tyrosine kinase, and binding to its ligand (hepatocyte growth factor [HGF]) induces downstream signaling through the RAS-RAF and phosphoinositide 3-kinase (PI3K) pathways
      • aberrant MET signaling drives tumor growth through increased cell proliferation, survival, invasion, and metastasis

Reference:

1. Paik PK, Felip E, Veillon R, et al. Tepotinib in Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations. N Engl J Med. 2020;383(10):931-943. doi:10.1056/NEJMoa2004407
2. NICE (May 2022). Tepotinib for treating advanced non-small-cell lung cancer with MET gene alterations