Landscape of Savolitinib Development for the Treatment of Non-Small Cell Lung Cancer with MET Alteration—A Narrative Review

Zhu, Xiaokuan; Lu, Yao; Lü, Shun

doi:10.3390/cancers14246122

Cited by 14 publications

(10 citation statements)

References 87 publications

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“…Savolitinib, a highly selective small-molecule MET-TKI, received conditional approval by the China National Medical Products Administration (NMPA) in 2021 for the clinical treatment of NSCLC with MET exon 14 skipping mutations. [6][7][8] Previous reports have also indicated that savolitinib is effective in NSCLC patients with MET amplification after previous treatment with EGFR-TKIs. 9 However, the efficacy of MET-TKIs, especially savolitinib, is not fully assessed in MET fusion-positive NSCLC.…”

Section: Discussionmentioning

confidence: 99%

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

Ouyang,

Shu,

Xue

et al. 2024

OTT

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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.

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Section: Discussionmentioning

confidence: 99%

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

Ouyang,

Shu,

Xue

et al. 2024

OTT

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“…MET is known as the hepatocyte growth factor receptor and is located at the long arm of chromosome 7( 75 ). MET contributes to nerve and muscle formation and is involved in embryogenesis and wound healing.…”

Section: Gene Mutation and Targeted Therapy In Sub-centimeter Lung Ca...mentioning

confidence: 99%

Advancements in the diagnosis and treatment of sub‑centimeter lung cancer in the era of precision medicine (Review)

Wang,

Shi,

Liu

2024

Mol Clin Oncol

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Lung cancer is the malignancy with the highest global mortality rate and imposes a substantial burden on society. The increasing popularity of lung cancer screening has led to increasing number of patients being diagnosed with pulmonary nodules due to their potential for malignancy, causing considerable distress in the affected population. However, the diagnosis and treatment of sub-centimeter grade pulmonary nodules remain controversial. The evolution of genetic detection technology and the development of targeted drugs have positioned the diagnosis and treatment of lung cancer in the precision medicine era, leading to a marked improvement in the survival rate of patients with lung cancer. It has been established that lung cancer driver genes serve a key role in the development and progression of sub-centimeter lung cancer. The present review aimed to consolidate the findings on genes associated with sub-centimeter lung cancer, with the intent of serving as a reference for future studies and the personalized management of sub-centimeter lung cancer through genetic testing.

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“…There are a few more type Ib Met TKIs currently under clinical investigation, (savolitinib, APL-101, and SAR125844). Savolitinib (also known as AZD6094 and volitinib) is a highly selective Met TKI that is conditionally approved in China for advanced NSCLC with MET-exon-14-skipping mutations [89]. In a pivotal phase 2 trial (NCT02897479), savolitinib as a monotherapy demonstrated notable clinical responses and a well-tolerated safety profile in Chinese patients with pulmonary sarcomatoid carcinoma (PSC), brain metastasis, and other NSCLC subtypes positive for MET exon 14 mutations [90].…”

Section: Type Ib Met Tkismentioning

confidence: 99%

MET-Targeting Anticancer Drugs—De Novo Design and Identification by Drug Repurposing

Leung

Cho

2023

DDC

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The Met protein is a cell surface receptor tyrosine kinase predominantly expressed in epithelial cells. Aberrant regulation of MET is manifested by numerous mechanisms including amplification, mutations, deletion, fusion of the MET proto-oncogene, and protein overexpression. They represent the common causes of drug resistance to conventional and targeted chemotherapy in numerous cancer types. There is also accumulating evidence that MET/HGF signaling drives an immunosuppressive tumor microenvironment and dampens the efficacy of cancer immunotherapy. Substantial research effort has been invested in designing Met-targeting drugs with different mechanisms of action. In this review, we summarized the current preclinical and clinical research about the development of Met-targeting drugs for cancer therapeutics. Early attempts to evaluate Met-targeted therapies in clinical trials without selecting the appropriate patient population did not produce satisfactory outcomes. In the era of personalized medicine, cancer patients harboring MET exon 14 alterations or MET amplification have been found to respond well to Met-inhibitor therapy. The application of Met inhibitors to overcome drug resistance in cancer patients is discussed in this paper. Given that kinases play critical roles in cancer development, numerous kinase-mediated signaling pathways are attractive targets for cancer therapy. Existing kinase inhibitors have also been repurposed to new kinase targets or new indications in cancer. On the other hand, non-oncology drugs have also been repurposed for treating cancer through kinase inhibition as one of their reported anticancer mechanisms.

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Landscape of Savolitinib Development for the Treatment of Non-Small Cell Lung Cancer with MET Alteration—A Narrative Review

Cited by 14 publications

References 87 publications

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

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

Advancements in the diagnosis and treatment of sub‑centimeter lung cancer in the era of precision medicine (Review)

MET-Targeting Anticancer Drugs—De Novo Design and Identification by Drug Repurposing

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