Improved Survival Outcomes in Patients With MET-Dysregulated Advanced NSCLC Treated With MET Inhibitors: Results of a Multinational Retrospective Chart Review

Clin Lung Cancer. 2023 Nov;24(7):641-650.e2. doi: 10.1016/j.cllc.2023.08.011. Epub 2023 Aug 13.

Abstract

Background: We evaluated the disease and patient characteristics, treatment, and MET testing patterns, predictive biomarkers and survival outcomes in patients with MET-dysregulated metastatic non-small-cell lung cancer (NSCLC) in a real-world setting.

Patients and methods: This was a multinational, retrospective, noninterventional chart review study. Data from medical records of patients with advanced/metastatic EGFR wild-type, MET-dysregulated NSCLC (December 2017-September 2018) were abstracted into electronic data collection forms.

Results: Overall, 211 patient charts were included in this analysis; 157 patients had MET exon 14 skipping mutations (METex14; with or without concomitant MET amplification) and 54 had MET amplification only. All patients were tested for METex14, whereas MET amplification was evaluated in 168 patients. No overlap was reported between MET dysregulation and ALK, ROS1 or RET rearrangements, or HER2 exon 20 insertions. Overall, 56 of 211 patients (26.5%) received MET inhibitor (METi) therapy in any treatment-line setting (31.2% in the METex14 cohort; 13% in the MET-amplified only cohort). In the METex14 cohort, median OS in patients receiving METi was 25.4 months versus 10.7 months in patients who did not (HR [95% CI]: 0.532 [0.340-0.832]; P = .0055). In the MET-amplified only cohort, median OS was 20.6 months in patients treated with METi compared with 7.6 months in those without METi (HR [95% CI]: 0.388 [0.152-0.991]; P = .0479).

Conclusions: MET alterations in NSCLC typically occur in the absence of other oncogenic driver mutations and are associated with poor survival outcomes. Notably, METi therapies are associated with improved survival outcomes in patients with MET-dysregulated NSCLC.

Keywords: MET mutations; Non-small cell lung cancer; Real-world study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Mutation / genetics
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-met / genetics
  • Retrospective Studies

Substances

  • Proto-Oncogene Proteins c-met
  • Proto-Oncogene Proteins
  • Protein Kinase Inhibitors