Response to Savolitinib in a Patient with Advanced Poorly Differentiated Lung Carcinoma Positive for a Novel EML4-MET Gene Fusion

Abstract

Background

Cellular-mesenchymal to epithelial transition factor (c-MET) alterations have significant therapeutic implications in non-small cell lung cancer (NSCLC). Although MET fusion is a rare genomic event, advances in detection technologies have enabled the identification of various MET fusion partner genes. However, standard therapeutic options for MET fusion in NSCLC cases remain undefined. This report presents a novel fusion variant, EML4-MET, encompassing exons 1 to 13 of EML4 and exons 15 to 21 of MET, including the entire MET kinase domain, and discusses the response of this case to savolitinib treatment.

Case Presentation

A 65-year-old woman was diagnosed with advanced poorly differentiated lung carcinoma. Molecular profiling of circulating tumor DNA (ctDNA), carried out by next-generation sequencing (NGS), identified a novel EML4-MET fusion. The patient was administered the MET receptor tyrosine kinase inhibitor savolitinib at 400 mg daily. One month later, computed tomography (CT) revealed some lesions with volume reduction. However, COVID-19 diminished the efficacy of savolitinib. Regrettably, the patient succumbed to respiratory and circulatory failure due to disease progression in March 2023.

Conclusion

This case uncovers a new type of MET fusion and expands the range of potential MET fusion targets in NSCLC. The patient responded to savolitinib, suggesting a reference basis for the treatment of similar cases with EML4-MET fusion in the future. Additional research is warranted to assess the biological significance of the EML4-MET fusion in NSCLC.

Keywords:

• non-small cell lung cancer
• EML4-MET
• savolitinib

Data Sharing Statement

The data will be shared on reasonable request to the corresponding author.

Ethics Approval and Consent to Participate

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by Ethics committee on Biomedical Research, West China Hospital of Sichuan University (2023-2236). All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Consent for Publication

Written Informed Consent for publication has been obtained from patient.

Acknowledgments

The authors thank the academic support from OrigiMed Diagnostics.

Disclosure

The authors declare that they have no competing interests.

Additional information

Funding

There is no funding to report.