Understand Met14 outer Xianzi jump mutation NSCLC: What clinical and pathological characteristics of these patients are these patients?

*For medical professionals for reading reference

New Chinese patient data, let's take a look at what inspiration is.

In recent years, targeted therapy has brought great benefits to the treatment of non -small cell lung cancer (NSCLC) that drives gene mutations, and has allowed countless patients to extend survival. In addition to the common target epidermal growth factor receptor (EGFR) and interception lymphoma (ALK), interstitial-epithelial cell conversion factor (MET) has gradually become a new target with potential. How to identify such patients more efficiently in clinical practice? This article will interpret the clinical and pathological characteristics of patients with NSCLC patients at MET14.

Met14 outer appende jump mutation is one of the driving factor of malignant tumors

The C-MET protein encoded by MET gene is a transgender tyrosine kinase receptor that can combine with its ligand-hepatocyte growth factor (HGF) to activate a series of signal pathways in the downstream, participate in regulating cell proliferation and production of cells , Migration and vascular production. Once the MET pathway occurs abnormal, these cell function will also be abnormal.

The No. 14 outer appende C-MET of the MET gene is a key structure of protein degradation. The lack of fragments will cause abnormal activation of the downstream signal pathway. If cancer cells have jumping and mutations outside MET14, it will promote the proliferation, migration, vascular abnormalization, and apoptosis in the cancer cells, and eventually drive the occurrence and development of malignant tumors.

What are the current treatment methods for patients with meticulous jumping mutations in MET14?

With the emergence of MET inhibitors and newly developed multi -target small molecules inhibitors, the treatment of patients with jumping mutations in MET14 has a more accurate choice.

Sevotinib became the first domestic targeted medicine to be approved by MET14 in 2021, and has since opened a new situation of domestic MET targeted therapy. Study data shows that Savacibini treats the survival of Saivinib therapy. The benefit is obvious, and the general total survival period (OS) of the general population reaches 12.5 months, and the mid-to-no progressive survival period (PFS) is 6.9 months [1-2]. In addition, Capmatinib and TEPOTINIB have been approved by the US Food and Drug Administration (FDA) for treatment of patients with NSCLC patients with MET14 outer jumping mutations. More MET inhibitors such as Vesicinib are also being developed.

What clinical pathological characteristics are there in patients with MET14 outer appendal jumping mutations?

Recently, a paper published by scholars in my country [3] summarized the typical clinical characteristics and different treatment methods of patients with NSCLC patients in MET14, in order to provide certain reference value for future treatment.

Researchers reviewed the medical records of 763 patients with NSCLC patients from Guangdong Medical University from 2018 to 2021, and identified 11 patients with jumping mutations with MET14 outer appearance. Subsequently, the clinical data including symptoms and diagnosis, imaging, and follow -up analysis of the pathology and related clinical information were performed.

Of these 11 patients, 9 were men and 2 were women. The age range is 69-85 years old, which are diagnosed with lung glandular ingraper carcinoma (IVB stage, 1 case), pulmonary adenocarcinoma (stage IV, 6 cases; period IIIA, 1 case), pulmonary tumor-like cancer (stage IV, 3 example). 8 patients had metastasis, including 3 cases of liver metastasis, 4 cases of lymph node metastasis, and 1 case of chest metastasis and pericardial metastasis. MET gene mutation methods include alkali -based replacement, insertion, and lack of large segments. Three of the 11 patients were stable before the follow -up, and 4 died within one year. Among these four patients, patients who received selective MET inhibitors survived for more than 7 months.

The researchers have made the following summary:

Met14 out -of -appearance jump mutations may be more common among male patients, but there are differences in different research reports. At present, there is no conclusion, and the sample samples in this article are small, and further research needs to be studied.

Driven gene positive may be the contraindication of immunotherapy for patients with metastatic NSCLC, because even if PD-L1 has a high level of PD-L1 in NSCLC patients, it is not good for immunotherapy. The results of immunotherapy in patients with NSCLC patients outside MET14 are unclear, and more data clarification is urgently needed.

At present, the method of second-generation sequencing (NGS) is based on AMPLICON-BASED methods, Hybrid Capture methods, and molecular unique identifiers (UID) labeling method. Considering the diversity of MET14 outer submissives and the potential positions of these mutations in the MET gene, the choice of detection methods, hybrid capture method is the preferred method of avoiding common analogy -based genes based on the detection method of amplification.

For the formulation of first -line treatment plan for patients with MET14 outer appendes, the first -line treatment plan for patients with NSCLC should comprehensively consider factors such as drug selection, treatment duration, and adverse reactions. A comprehensive management model can be considered. For patients with good condition control, for example, PR patients can combine surgery or three -dimensional directional radiation therapy (SBRT).

With the widespread application of small molecules inhibitors, the mechanism of obtaining drug resistance in patients still needs to be further explored and analyzed.

Overall, the clinical pathological characteristics of patients with MET14 outer jumping mutations NSCLC still need to be further verified in more research. In clinical practice, patients with different gender and smoking history should be paid to the mutation status of MET14 exogenous appendes. Troop

Precision treatment and testing are advanced. Met No. 14 outer Xianzi jump mutation detection has obtained a clear recommendation from many domestic and foreign guidelines. In the "Guidelines for Clinical Practice (2021)" [4] [4], MET14 outer sub -jump mutations are listed as "compulsory genes" in MET14. Moreover, in the 2022 version of the China Clinical Oncology Society (CSCO) NSCLC Diagnosis and Treatment Guide [5], the test recommendation level of the MET14 outer Xianzi jump mutation has been increased from the II -level recommendation of the 2021 Guide to II. In addition, in 2022, the 3rd edition of the National Comprehensive Cancer Network (NCCN) Guide [6] recommends that Met14 outer Xianzi jump mutation is one of the biomarkers of "minimum detection" of patients with metastatic non -scale NSCLC. The importance and EGFR , ALK, ROS1 and other genetic mutations are the same as PD-L1 expression.

It can be seen that the importance of clinical clinical clinical is beyond doubt that MET14's out-of-appearance jump mutation testing is beyond doubt, especially with the continuous research and development of various MET-TKIs, the prognosis of MET14 outer appende jumping mutations NSCLC has improved, so clinical clinical clinicals Doctors should further strengthen the attention of the target detection, so that patients will benefit from accurate treatment to the greatest extent.

references:

[1]]Lu S, Fang J, Li X, et al. Once-daily savolitinib in Chinese patients with pulmonary sarcomatoid carcinomas and other non-small-cell lung cancers harbouring MET exon 14 skipping alterations: a multicentre, single-arm, Open-Label, Phase 2 Study [J]. Lancet Respir Med. 2021; 9 (10): 1154-1164.

[2] lu s, et al. Final OS Results and subgroup analysis of savolitinib in patients with meton 14 Skipping Mutations (METEX14+) nsclc. ELCC 2022, 2mo.

[3] Chen, H, Luo, Y, Lin, M, Et Al. Clinical and Pathology Characteristics of 11 NSCLC Patients with C-Met Exon 14 Skipping. Translational Cancer Research, 11 (4), 880–887.

[4] Chinese Medical Society Pathology Branch, National Pathological Quality Control Center, Lung Cancer Group of the Chinese Medical Society on Cancer Branch, etc., etc. , 2021,50 (4): 323-332.

[5] Guide Working Committee of the China Clinical Oncology Society. China Clinical Oncology Society (CSCO) non -small cell lung cancer diagnosis and treatment guide 2022 [M]. Beijing: People's Health Publishing House.

[6] NCCNGUIDEELINEESION3.2022, Non-SmallCellungcancer.

This material is provided by Astrikon, for reference for medical professionals

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