Targeting MET in NSCLC: An Ever-Expanding Territory

Han, Ying; Yu, Yinghui; Miao, Da; Zhou, Mo; Zhao, Jing; Shao, Zhehua; Jin, Rui; Le, Xiuning; Li, Wen; Xia, Yang

doi:10.1016/j.jtocrr.2023.100630

JTO Clinical and Research Reports

2024

DOI: 10.1016/j.jtocrr.2023.100630

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Targeting MET in NSCLC: An Ever-Expanding Territory

Ying Han,

Yinghui Yu,

Da Miao

et al.

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2024

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Cited by 6 publications

References 92 publications

(126 reference statements)

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Savolitinib conferred sensitivity in a patient with D1228H mutation-induced capmatinib-resistant MET exon 14 skipping mutated lung adenocarcinoma

Li,

Lu,

Zhao

et al. 2024

J Cancer Res Clin Oncol

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Traditionally, the D1228 E/G/H/N mutation has been thought to cause Type I MET-TKI resistance. We reported a 75-year-old female with non-small cell lung cancer harboring MET exon 14 skipping mutation, who developed acquired MET D1228H mutation induced by capmatinib treatment. Interestingly, the patient demonstrated marked response to second-line savolitinib treatment with the duration of response of 19 months and several additional metastatic lesions appeared. Pathological assessment of rebiopsy sample showed adenocarcinoma and targeted next-generation sequencing revealed the loss of MET D1228H mutation and presence of MET p.Y1230N mutation. In response, the treatment regimen was amended to include a daily administration of 60 mg of cabozantinib, which resulted in moderate size reduction of the tumours. The switch of resistance mutations indicated that different type Ib MET inhibitors may exhibit distinct mechanisms of resistance. We call for futher studies on resistance based on patient-derived pre-clinical models including patient-derived tumor-like cell clusters, patient-derived organoids, and patient-derived xenografts.

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Savolitinib conferred sensitivity in a patient with D1228H mutation-induced capmatinib-resistant MET exon 14 skipping mutated lung adenocarcinoma

Li,

Lu,

Zhao

et al. 2024

J Cancer Res Clin Oncol

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Precision nanomedicine to treat non-small cell lung cancer

Dessai,

Nayak,

Nayak

2024

Life Sciences

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Clinical Utility of a Circulating Tumor Cell–Based Cerebrospinal Fluid Assay in the Diagnosis and Molecular Analysis of Leptomeningeal Disease in Patients With Advanced Non–Small Cell Lung Cancer

Malhotra,

Muddasani,

Fricke

et al. 2024

JCO Precis Oncol

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PURPOSE Leptomeningeal disease (LMD) is associated with significant morbidity and mortality for metastatic non–small cell lung cancer (NSCLC). We describe our clinical experience in evaluating the use of cerebrospinal fluid (CSF)–derived circulating tumor cells (CTCs) for the diagnosis of LMD and the detection of genomic alterations in CSF cell-free DNA (cfDNA). METHODS Patients with NSCLC who had CSF collection as part of routine clinical care for suspected LMD were included in the study. CSF was evaluated for CTCs and cfDNA using a commercial assay (CNSide; Biocept, San Diego, CA), and molecular profiling was performed. Molecular testing results from sequencing of tumor tissue and plasma circulating tumor DNA were collected. cMET and human epidermal growth factor receptor 2 (HER2) expression analysis was performed using fluorescence in situ hybridization (FISH). RESULTS Twenty-two patients were included (77% female; median age 60 years). Sixty-four percent had sensitizing EGFR mutations, and 32% had an atypical EGFR mutation. Thirteen of the 22 patients (59%) were diagnosed with LMD using the CSF CTC assay. Five of these 13 patients (38%) had negative CSF cytology for LMD, and two patients (15%) had normal magnetic resonance imaging brain imaging. Seven of the 13 patients (54%) had sufficient CTCs to perform molecular profiling. The concordance with tissue next-generation sequencing was 100%, and the driver mutation was identified in all seven patients with the CSF cfDNA assay. cMET expression and HER2 expression via FISH were noted in 11 patients (50%) and four patients (18%) respectively. CONCLUSION We detected higher sensitivity to diagnose LMD using CSF CTC-based assay; 38% of LMD cases identified using this assay were missed by standard CSF cytology. CSF molecular testing using CSF cfDNA demonstrated high concordance with tissue-based molecular testing.

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Targeting MET in NSCLC: An Ever-Expanding Territory

Cited by 6 publications

References 92 publications

Savolitinib conferred sensitivity in a patient with D1228H mutation-induced capmatinib-resistant MET exon 14 skipping mutated lung adenocarcinoma

Savolitinib conferred sensitivity in a patient with D1228H mutation-induced capmatinib-resistant MET exon 14 skipping mutated lung adenocarcinoma

Precision nanomedicine to treat non-small cell lung cancer

Clinical Utility of a Circulating Tumor Cell–Based Cerebrospinal Fluid Assay in the Diagnosis and Molecular Analysis of Leptomeningeal Disease in Patients With Advanced Non–Small Cell Lung Cancer

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