Targeted therapy for <i>МЕТ</i>-positive non-small cell lung cancer

Abstract

Opportunities in the treatment of patients with metastatic non-small cell lung cancer (NSCLC) are expanding every year. New targets are em erging for molecular-directed antitumor therapy, the so-called targeted therapy. One of such promising targets is damage to the MET gene. Taking into account the large number of active targets in NSCLC, the time factor and the limited amount of tumor material, conducting extensive genomic testing using NGS is preferable to routine diagnostic methods.Mutation in the form of omission of the 14 exon of MET (METex14) occurs with a frequency of 3–4%, amplification of the MET gene – in 2–4% of cases. There is evidence that these disorders correlate with a poor prognosis. At the same time, the METex14 mutation and a high level of copyness are potential predictor markers for the response to capmatinib. For molecular genetic testing, the next-generation sequencing method is optimal, which makes it possible to detect multiple, including rare disorders. Capmatinib is a low molecular weight selective reversible MET inhibitor. In preclinical studies, the drug proved effective against various types of activation of the MET signaling pathway. Clinical studies have confirmed its high antitumor activity. In the GEOMETRY mono1 study, the objective response (OR) in patients with the METex14 mutation as the first line was among 68%, in pretreated patients – 41%, with a median response duration of 12.6 months and 9.7 months, respectively. The drug demonstrated high intracranial activity, regardless of whether radiation therapy was previously performed or not. Objective antitumor response and clinical improvement to targeted therapy with capmatinib are realized fairly quickly. The results obtained during the clinical trial were reproduced in routine practice. The drug has an acceptable toxicity profile. Capmatinib is the first and so far the only drug in the Russian Federation approved for the treatment of patients with a mutation of the MET gene.