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MET-Targeted Therapies and Clinical Outcomes: A Systematic Literature Review
Yiting Dong1, Jiachen Xu1, Boyang Sun1
1State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Pan-jia-yuan South Lane, Chaoyang District, Beijing, 100021, China.
Introduction:
Numerous therapeutic agents specifically targeting the mesenchymal-epithelial transition (MET) oncogene are being developed.
Objective:
The aim of the current review was to systematically identify and analyze clinical trials that have evaluated MET inhibitors in various cancer types and to provide an overview of their clinical outcomes.
Methods:
An electronic literature search was carried out in the PubMed and Embase databases to identify published clinical trials related to MET inhibitors. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was followed for the systematic appraisal of the literature. Data related to clinical outcomes, including progression-free survival, overall survival, objective response rate, and overall tumor response, were extracted.
Results:
In total, 49 publications were included. Among these, 51.02% were phase II studies, 14.28% were randomized controlled trials, three were phase III studies, two were prospective observational studies, and the remainder were either phase I or Ib studies. The majority (44.89%) of articles reported the clinical outcomes of MET inhibitors, including small molecules, monoclonal antibodies, and other agents, in patients with non-small-cell lung cancer (NSCLC) harboring MET alterations. MET amplification, overexpression, and MET exon 14 skipping mutations were the major MET alteration types reported across the included studies. Clinical responses/outcomes varied considerably.
Conclusion:
This systematic literature review provides an overview of the literature available in Embase and PubMed regarding MET-targeted therapies. MET-selective tyrosine kinase inhibitors (TKIs) (capmatinib, tepotinib, and savolitinib) may become a new standard of care in NSCLC, specifically with MET exon 14 skipping mutations. A combination of MET TKIs with epidermal growth factor receptor (EGFR) TKIs (osimertinib + savolitinib, tepotinib + gefitinib) may be a potential solution for MET-driven EGFR TKI resistance. Further, MET alteration (MET amplification/overexpression) may be an actionable target in gastric cancer and papillary renal cell carcinoma.
Insights
MET inhibitors show promise for treating various cancers, particularly non-small cell lung cancer with MET exon 14 skipping mutations. Further research into MET-targeted therapies may establish new standards of care.
Area of Science:
- Oncology
- Molecular Biology
- Clinical Pharmacology
Background:
- The mesenchymal-epithelial transition (MET) oncogene is a target for numerous developing cancer therapeutics.
- Understanding the clinical efficacy of MET inhibitors across different cancer types is crucial for advancing treatment strategies.
Purpose of the Study:
- To systematically review and analyze clinical trials evaluating MET inhibitors in various cancers.
- To provide an overview of the clinical outcomes associated with MET-targeted therapies.
Main Methods:
- Systematic literature search conducted in PubMed and Embase databases.
- Adherence to PRISMA guidelines for literature appraisal.
- Extraction of clinical outcomes including progression-free survival, overall survival, and objective response rate.
Main Results:
- Analysis of 49 publications, predominantly phase II studies, evaluating MET inhibitors.
- Non-small cell lung cancer (NSCLC) with MET alterations (amplification, overexpression, exon 14 skipping) was the most reported indication.
- Clinical responses to MET inhibitors demonstrated considerable variability across studies.
Conclusions:
- MET-selective tyrosine kinase inhibitors (TKIs) like capmatinib, tepotinib, and savolitinib show potential as a new standard of care for NSCLC with MET exon 14 skipping mutations.
- Combinations of MET TKIs with EGFR TKIs may overcome resistance mechanisms.
- MET alterations represent actionable targets in gastric cancer and papillary renal cell carcinoma.
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