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Updated: May 25, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Patients With Advanced Non-small Cell Lung Cancer Harboring MET Alterations: A Descriptive Cohort Study
Dina Oksen1, Emmanuelle Boutmy1, Yuexi Wang2
1Department of Epidemiology, the healthcare business of Merck KGaA, Darmstadt, Germany.
Purpose:
Mesenchymal-epithelial transition factor (MET) alterations are rare oncogenic drivers in patients with non-small cell lung cancer (NSCLC). This study characterized patients with advanced NSCLC harboring MET exon 14 (METex14) skipping and MET amplification (METamp) in routine clinical practice in the United States.
Patients And Methods:
Using electronic medical record data from the ConcertAI Oncology Dataset (2004-2022), 2 patient cohorts were identified: 1 with METex14 skipping with or without METamp, and 1 with METamp without METex14 skipping. A subgroup with METamp and concomitant epidermal growth factor receptor (EGFR) mutations who had received EGFR-tyrosine kinase inhibitors (TKIs) was also analyzed. Patient characteristics, treatment patterns and outcomes were described.
Results:
93 patients with advanced NSCLC harboring METex14 skipping and 164 with advanced NSCLC harboring METamp were identified. Established oncogenic drivers other than MET were less frequent in the METex14 skipping cohort than the METamp cohort. In both cohorts, first-line chemotherapy use decreased over time while immune checkpoint inhibitor (ICI) and MET inhibitor use increased. Treatment patterns were heterogeneous, with patients receiving multiple drug classes across therapy lines. Outcomes were better for patients with METex14 skipping NSCLC who received targeted therapies or ICIs versus chemotherapy. Subgroup analyses of EGFR-TKI-treated patients with METamp indicated poor outcomes.
Conclusion:
Patients with METex14 skipping and/or METamp NSCLC require targeted and personalized treatment approaches to optimize treatment effect and have an unmet medical need. With targeted therapies recently available and others under exploration, treatment outcomes could significantly improve for patients with NSCLC harboring these rare drivers.
Insights
Mesenchymal-epithelial transition factor (MET) alterations, including MET exon 14 skipping and MET amplification, are rare in non-small cell lung cancer (NSCLC). Personalized treatments, particularly targeted therapies and immune checkpoint inhibitors, show improved outcomes for MET-altered NSCLC patients.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Mesenchymal-epithelial transition factor (MET) alterations are rare but significant oncogenic drivers in non-small cell lung cancer (NSCLC).
- Understanding the clinical characteristics, treatment patterns, and outcomes of patients with MET exon 14 (METex14) skipping and MET amplification (METamp) is crucial for personalized medicine.
Purpose of the Study:
- To characterize patients with advanced NSCLC and METex14 skipping and/or MET amplification in a real-world clinical setting in the United States.
- To describe patient demographics, treatment strategies, and clinical outcomes associated with these rare genetic alterations.
Main Methods:
- Retrospective analysis of electronic medical record data from the ConcertAI Oncology Dataset (2004-2022).
- Identification and comparison of two patient cohorts: METex14 skipping (with or without METamp) and METamp without METex14 skipping.
- Subgroup analysis of patients with METamp and EGFR mutations treated with EGFR-tyrosine kinase inhibitors (TKIs).
Main Results:
- 93 patients with METex14 skipping and 164 with METamp were identified in advanced NSCLC.
- Decreased use of first-line chemotherapy over time, with increased use of immune checkpoint inhibitors (ICIs) and MET inhibitors.
- Improved outcomes for METex14 skipping NSCLC patients treated with targeted therapies or ICIs compared to chemotherapy; poor outcomes noted in EGFR-TKI-treated METamp subgroup.
Conclusions:
- Patients with METex14 skipping and/or METamp NSCLC have an unmet medical need requiring targeted and personalized treatment approaches.
- The availability of novel targeted therapies and ongoing research hold promise for significantly improving treatment outcomes in NSCLC patients with these rare drivers.
