Unfavorable response to capmatinib for MET exon14 skipping after first-line osimertinib in a patient with EGFR-mutated lung adenocarcinoma: A case report and literature review

Respir Investig. 2024 Jul;62(4):677-680. doi: 10.1016/j.resinv.2024.05.009. Epub 2024 May 21.

Abstract

MET exon14 skipping mutations (METex14s) are rarely reported as a potential resistance mechanism to EGFR tyrosine kinase inhibitors (TKIs). The efficacy of targeted therapy against METex14s emerging after osimertinib resistance is uncertain. Herein, we report a case of EGFR-mutated metastatic lung adenocarcinoma in which METex14 was detected in a re-biopsy upon first-line osimertinib resistance. The patient received capmatinib monotherapy as third-line therapy, which was ineffective, followed by an exceptional response to salvage therapy with afatinib. This report highlights the heterogeneity of EGFR-TKI resistance and that targeting rare resistance mechanisms remains challenging.

Keywords: Capmatinib; MET; Osimertinib; Resistance; exon14 skipping.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Acrylamides* / therapeutic use
  • Adenocarcinoma of Lung* / drug therapy
  • Adenocarcinoma of Lung* / genetics
  • Afatinib / administration & dosage
  • Afatinib / therapeutic use
  • Aniline Compounds* / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Benzamides / therapeutic use
  • Drug Resistance, Neoplasm* / genetics
  • ErbB Receptors* / genetics
  • Exons / genetics
  • Humans
  • Imidazoles
  • Indoles
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Male
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-met* / genetics
  • Pyrimidines
  • Salvage Therapy
  • Triazines / administration & dosage
  • Triazines / therapeutic use

Substances

  • Acrylamides
  • Afatinib
  • Aniline Compounds
  • Antineoplastic Agents
  • Benzamides
  • capmatinib
  • EGFR protein, human
  • ErbB Receptors
  • Imidazoles
  • Indoles
  • MET protein, human
  • osimertinib
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-met
  • Pyrimidines
  • Triazines