scholarly journals Responses to crizotinib and cabozantinib in patient with lung adenocarcinoma harboring mesenchymal-epithelial transition factor exon 14 skipping mutation

Medicine ◽  
2021 ◽  
Vol 100 (4) ◽  
pp. e24300
Author(s):  
Ruo-Yan Qin ◽  
Ling-Shuang Liu ◽  
Hui-Yong Zhang ◽  
Cheng-Hua Lu ◽  
Xiao-Yan Guo ◽  
...  
2021 ◽  
Vol 11 ◽  
Author(s):  
Hongge Liang ◽  
Dexun Zhou ◽  
Lin Dai ◽  
Moqin Zhang ◽  
Zhancheng Gao ◽  
...  

BackgroundThe c-mesenchymal–epithelial transition factor (C-MET) is an oncogene encoding a tyrosine kinase receptor that plays an important role in tumor growth and metastasis. The National Comprehensive Cancer Network (NCCN) guidelines have approved carbatinib/crizotinib for advanced non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping.MethodsIn June 2020, the Department of Respiratory and Critical Care Medicine of Peking University People’s Hospital admitted a 72-year-old male patient with lung adenocarcinoma (LADC) with a history of interstitial lung disease secondary to antineutrophil cytoplasmic antibody-associated vasculitis. Genetic examination by next-generation sequencing showed an intergenic fusion of MET, and crizotinib was administered on August 14, 2020. Follow-up showed that tumor volume was significantly reduced. However, crizotinib was discontinued in November 2020 because of the patient’s worsening interstitial lung disease, and CT scans showed continued partial response (PR) for 5 months. In April 2021, right lower lobe mass progressed, and disease progression was considered.ConclusionThis was the first case of a patient with LADC with MET intergenic fusion who significantly benefited from crizotinib. Even after crizotinib was discontinued for 5 months, the patient continued exhibiting PR, suggesting that MET intergenic fusion may have carcinogenic activity in LADC and was sensitive to crizotinib.


Bioanalysis ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 285-293
Author(s):  
Chunling Zhou ◽  
Jinmiao Tian ◽  
Peng Lin ◽  
Tianzhu Liu ◽  
Aiping He ◽  
...  

Aim: Capmatinib is an orally bioavailable mesenchymal-epithelial transition factor inhibitor with anticancer activity, which has proved preclinical activity in multiple cancer trials. The present study aimed to develop a fast and reliable assay approach to quantify capmatinib in rat plasma. Methodology & results: After protein precipitation with acetonitrile, the chromatographic separation was achieved with an Acquity UPLC BEH C18 column, and subsequently detected with positive electrospray ionization via a triple quadrupole tandem mass spectrometer. The target quantitative ion pairs m/z 412.99 → 381.84 for capmatinib and 387.00 → 355.81 for the internal standard, respectively. The calibration curve for the assay was linear over the range of 1.0–4000 ng/ml. Conclusion: The method shows an excellent performance in linearity, accuracy, precision, stability, and has been successfully applied to a pharmacokinetic study after oral administration of capmatinib at three doses (5, 10 and 20 mg/kg) in rats.


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