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CASE REPORT article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1489696
This article is part of the Research Topic The Molecular Mechanism in Anti-tumor Therapy Resistance View all 14 articles
Case Report: A novel MET exon 14 skipping mutation after EGFR-TKI resistance in advanced lung adenocarcinoma and sustained clinical response to Savolitinib
Provisionally accepted- West China Hospital, Sichuan University, Chengdu, China
Background: The MET proto-oncogene (MET) plays a crucial role as an oncogenic driver gene in non-small cell lung cancer (NSCLC). At present, numerous types of MET exon 14 (METex14) skipping mutation have been identified, but different splice variants often exhibit varying treatment responses. There is currently no standardized treatment approach for rare METex14 mutation after resistance to epidermal growth factor receptor tyrosine kinases inhibitor (EGFR-TKI). Herein, we present for the first time a case of advanced lung adenocarcinoma with a novel METex14 skipping mutation following resistance to EGFR-TKI and subsequent sensitivity to savolitinib. In addition, the patient developed a novel METex14 skipping mutation after EGFR-TKI resistance, which we suspect may be a potential new mechanism of EGFR-TKI resistance that has not been reported.Materials and methods: We conducted surgical specimen pathology diagnosis and next-generation sequencing (NGS) of peripheral blood to ascertain the patient's pathological and molecular characteristics.Results: NGS testing identified a novel METex14 (c.2888-23_2888-8del) skipping mutation in the patient with advanced lung adenocarcinoma who developed resistance to EGFR-TKI, suggesting its potential involvement as one of the mechanisms underlying the resistance to EGFR-TKI. Following administration of savolitinib with a daily dose of 400mg, the patient exhibited a partial response and achieved progression-free survival (PFS) exceeding 8 months.Conclusion: The case presents a novel METex14 skipping mutation that emerges subsequent to the progression of advanced lung adenocarcinoma following EGFR-TKI treatment. Importantly, this mutation may serve as one of the mechanisms contributing to resistance against EGFR-TKI and exhibit sensitivity towards savolitinib treatment, providing reference for future similar cases in terms of treatment options.
Keywords: novel MET exon 14 skipping mutation, EGFR-TKI resistance, Advanced lung adenocarcinoma, Savolitinib, Sustained clinical response
Received: 01 Sep 2024; Accepted: 24 Feb 2025.
Copyright: © 2025 Xue, Li, Li, Huang, Zhou and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qiang Wu, West China Hospital, Sichuan University, Chengdu, China
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