Remarkable pathological response to neoadjuvant tepotinib in lung adenocarcinoma with MET exon 14 skipping mutation: A case report

Thorac Cancer. 2024 Nov;15(32):2339-2343. doi: 10.1111/1759-7714.15459. Epub 2024 Sep 29.

Abstract

Mesenchymal-epithelial transition (MET) exon 14 (METex14) skipping mutation is a rare (3%-4%) driver mutation in non-small cell lung cancer (NSCLC). Tepotinib, a selective MET inhibitor, has shown promise in treating METex14 skipping-mutated NSCLC. However, its feasibility for perioperative application remains unclear. This report describes a 60-year-old man with stage IIIA (cT2N2M0) lung adenocarcinoma harboring a METex14 skipping mutation. After initial treatment with savolitinib was discontinued due to grade 4 transaminitis, the patient was switched to tepotinib, resulting in significant tumor regression. Six months later, further shrinkage was observed, and surgery revealed remarkable pathological response with no residual tumor in lymph nodes (ypT2N0M0, IB). Postoperative tepotinib continued, with no relapse at 6-month follow-up. This case highlights the potential of tepotinib as neoadjuvant therapy for resectable METex14 skipping-mutated NSCLC, warranting further clinical trials.

Keywords: MET exon 14 skipping mutation; neoadjuvant; non‐small cell lung cancer; tepotinib.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma of Lung* / drug therapy
  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / pathology
  • Exons*
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Neoadjuvant Therapy* / methods
  • Piperidines
  • Proto-Oncogene Proteins c-met* / genetics
  • Pyridazines
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use

Substances

  • tepotinib
  • Proto-Oncogene Proteins c-met
  • MET protein, human
  • Pyrimidines
  • Piperidines
  • Pyridazines