De Novo MET-amplified NSCLC treated with savolitinib achieved remarkable tumor regression - a case report and review of literature

Sep 23, 2026

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Primary MET amplification is an uncommon oncogenic driver in pulmonary tumors, and evidence for MET-tyrosine kinase inhibitor (TKI) therapy in de novo MET amplification remains limited. This case report describes an elderly patient with advanced lung adenocarcinoma harboring primary MET amplification. DNA-NGS showed high MET gene copy number with no other actionable alterations; MET FISH confirmed cluster amplification. Savolitinib achieved a sustained partial response for over sixteen months, supporting potential effectiveness and safety.

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Detailed case description

Journal of Cancer Research and Clinical Oncology (2025) 151:82 [https://doi.org/10.1007/s00432-025-06132-x](https://doi.org/10.1007/s00432-025-06132-x) CASE REPORT De Novo MET-amplified NSCLC treated with savolitinib achieved remarkable tumor regression: a case report and review of literature Jin Sheng1 · Juan Jiao2 · Na Yan3 · Hongming Pan1 Received: 30 September 2024 / Accepted: 1 February 2025 / Published online: 14 February 2025 © The Author(s) 2025 Abstract Primary MET amplification is an infrequent tumorigenic driver gene alteration identified in pulmonary neoplasms. Data on the effectiveness of MET-tyrosine kinase inhibitor (TKI) therapy in de novo MET amplification are relatively scarce, and there remains a dearth of empirical evidence supporting the use of precision therapy as first-line treatment for advanced non-small cell lung cancer (NSCLC) with primary MET amplification. We present a case of advanced lung adenocarcinoma in an elderly patient with primary MET amplification. The patient had an initial ECOG Performance Status (PS) 2. DNA-NGS analysis of tissue samples revealed a MET gene copy number (GCN) of 8, indicating MET amplification, without other oncogenic mutations associated with available drugs being detected. This finding was validated by MET fluorescence in situ hybridization (FISH), which showed cluster amplification. Initial treatment with savolitinib resulted in a sustained partial response lasting more than sixteen months. Our results suggest that savolitinib is effective and safe for the treatment of elderly patients with de novo amplified MET metastatic NSCLC and may therefore be considered a potential treatment option worthy of prospective study confirmation. Keywords Non-small cell lung cancer · Senior patients · Primary MET amplification · Targeted therapy · Case report · Review Introduction Receptor tyrosine kinase MET and its ligand hepatocyte growth factor (HGF), which act as oncogenic drivers in various human malignancies, often indicating aggressive disease and are associated with poor prognosis. (Cappuzzoet al. 2009; Di Renzo et al. 1995; Nakajima et al. 1999) Oncogenic alterations in the MET comprise MET exon 14 skipping mutations (METex14), elevated MET GCN, MET amplification, MET protein overexpression, MET-fusion 􀀍 Jin Sheng [shengjin@zju.edu.cn](shengjin@zju.edu.cn) 1 Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China 2 Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China 3 Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Dian Diagnostics Group Co., Ltd, Hangzhou, Zhejiang, China and MET mutations.(Recondo et al. 2020; Vansteenkiste et al. 2019) The incidence of de novo MET amplification in non-small cell lung cancer (NSCLC) ranges from 1 to 5% . METex14 usually do not occur simultaneously with EGFR, ROS1, BRAF, andALK variants.(Awad et al. 2016) Meanwhile, MET amplification was infrequent among NSCLC patients in China who lacked EGFR mutation, presenting a prevalence of approximately 1%.(Song et al. 2017) However, MET amplification has been identified as a secondary mechanism of resistance in NSCLC patients with EGFR mutations who acquire resistance to EGFR-tyrosine kinase inhibitors (TKIs) . (Sequist et al. 2020) Despite the low incidence of primary MET amplification in lung cancer, its oncogenic potential highlights the need for targeted treatments instead of resorting to options for driver gene negative lung cancer. Currently, FDA approved TKIs that target METex14 include capmatinib,(Dagogo-Jack et al. 2021; Wolf et al. 2020a, b) and tepotinib. (Paik et al. 2020; Wu et al. 2020) The efficacy of these TKIs in primary METamplified NSCLC was less favorable, with median PFS of 4.2–6.7 months and ORR of 40-41.7% in de novo high-level MET amplification identified by MET-fluorescenc

FAQs

What genetic alteration was identified in this NSCLC case?

DNA-NGS detected a high MET gene copy number indicating MET amplification, and MET FISH validated cluster amplification.

What treatment was used and how did the patient respond?

The patient received savolitinib as initial therapy and achieved a sustained partial response lasting more than sixteen months.

Why is de novo MET amplification clinically important in this context?

Although rare, primary MET amplification has oncogenic potential, and there is limited evidence supporting precision first-line use of MET-targeted TKI therapy in advanced NSCLC.

Sep 23, 2026

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