Quickly effective and lasting benefits, Savidi helps the primary meta to expand metastatic lung cancer patients quickly reverse the trend

*For medical professionals for reading reference

MET amplification patients cannot tolerate chemotherapy due to physical condition. How to use genetic testing and guidance?

This case is a patient with patients with pulmonary adenocarcinoma stage. It was previously intended to use Arotinib combined with chemotherapy. Holochemically chemotherapy. The number of patients in the second -generation sequencing (NGS) of the patient increases the number of copies of the MET gene, and the fluorescent in situ hybrid (FISH) test is further verified as the local amplification. Subsequently, the patient was suspended before the Aurotinib was treated with MET inhibitors, and the treatment was quickly effective after treatment. The bone pain was significantly alleviated compared to the previous. Difficulties in breathing have been significantly relieved. Since the follow -up, the case has been used for more than July, and it has continued to benefit. The case was provided by Professor Wang Jian of Jiangsu Provincial People's Hospital and invited Professor Su Mei of Jiangsu Provincial People's Hospital to comment.

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Basic Information:

Patient, male, 64 years old. On September 29, 2021, he was visited in a hospital in Nanjing.

Prosecution: cough, sputum, blood in sputum with chest pain in month.

Previous history: 30 years of silicon lung history, 30 years of smoking history, 10/day, no drug allergies, no other past medical history, intermittent fever during the period, can be descended by itself, the highest body temperature is 38.3 degrees Celsius.

Provide experts

Professor Wang Jian: The increased number of MET genes obtained by NGS detection cannot be directly understood as MET amplification, and the degree of MET amplification affects the efficacy of MET inhibitors

Met gene mutation may cause C-MET protein to fail to degrade, excessively activate or excessive expression, which leads to abnormal activation of the MET pathway. The main ways of MET gene mutation include MET 14 exogenous sub -jumping mutations, MET gene amplification, meta kinase domain mutations, and MET gene fusion [1]. Among them, the MET gene amplification includes primary amplification and secondary/co -driving amplification. Generally speaking, the higher the degree of MET amplification, the lower the proportion of other mutations, and the higher the drivingability [2].

So far, a variety of platforms have been used for MET gene copy number detection to evaluate MET status. FISH is the standard method for detecting MET amplification, which can distinguish between local amplification and multi -twice; NGS can simultaneously detect other mutations such as MET mutations and fusion, and can achieve multi -gene coexistence, but may miss MET multi -body [3] Essence The increase in the number of MET copies detected by the NGS is equivalent to the amplification of MET in the classic sense and is not conclusive.

The MET gene copy number is a continuous variable, so the setting of its positive threshold will affect the frequency of occurrence, the overlap rate of other gene subtypes, and the ability to predict the efficiency prediction index as the MET inhibitor. If MET variation is detected by the FISH method, the GCN≥5 is defined as MET amplification. 4].

In this case, the patient NGS testing indicates that the MET amplification CNV value is 4.52 times. In order to further determine whether it is MET amplification and the degree of MET, the pathology department will be verified for patients after consultation. Fish prompts MET/CSP7 & 2.2, which is a local amplification. It is speculated that patients can benefit from MET inhibitors.

In the past multiple MET amplification clinical studies, the entry conditions are MET amplification confirmed by FISH. And the higher the degree of MET amplification, the higher the response rate after receiving the treatment of MET inhibitors [5-8].

Savininib is a oral high-selective small molecule MET-TKI. Clinical studies have confirmed that Savidi has a good anti-tumor activity among MET amplification patients [9-10]. TATTON research shows that for EGFR-TKI treatment, the non-small cell lung carcinoma (NSCLC) patients who have enlarged MET have a good and lasting effect of the Saverninininininia combined with Oshitininib. [11] As a result, the patients followed the treatment plan for Savininib. After 5 days, the patient's condition improved significantly, and the adverse response was mild. At present, patients still maintain Saverninib therapy, and it has benefited more than July so far, and has continued to benefit.

Case review expert

Professor Su Mei: For the late NSCLC of MET amplification, Savidi treatment is safe and effective

At present, NSCLC targeted therapy has entered a standardized stage. With the continuous deepening of target genetic studies for available medications, MET drive gene mutations have attracted much attention. The 2022 version of "CSCO non -small cell lung cancer diagnosis and treatment guidelines" [12] Recommended NSCLC patients to undergo MET amplification test, provide guidance for patients' precise treatment, and then guide patients to receive MET inhibitors targeted therapy.

Clinically, in order to better judge the details of MET copies, it is not enough to use NGS detection. "Second -generation sequencing technology in the clinical application of Chinese experts in NSCLC (2020 version)" [13] pointed out that NGS has certain limitations in the detection of some mutant types such as copy number amplification. For some genetic variations that may not be detected accurately, a reliable monocular detection method should be considered to verify the variation detected by NGS.

After the patients in this case were tested in the early stage, the FISH test was added, and the number of copies of MET was detected in detail, laying a solid foundation for the next precise treatment. Bring rapid relief. The treatment process of this case prompts that Savidinib can be used as a preferred choice for clinical treatment for the metastatic NSCLC metastatic patients with metastasis. In the era of precision treatment, precision testing is the prerequisite for precision treatment. With the development of accurate treatment of lung cancer, MET amplification will play an increasingly important role in guiding treatment, evaluation efficacy, and judgment prognosis. In the future, it is hoped that more and more targeted drugs that are as efficient as Savinib can be put into clinical use, bringing more benefits and treatment options to patients with lung cancer in my country. In addition, the development and application of new inhibitors will also benefit more patients.

Introduction to experts

Dr. Chang Wang Jian

Male, doctor of medicine, deputy chief physician. Long -term clinical diagnosis and treatment of lung cancer, lung infection, asthma, chronic obstructive pulmonary disease and interstitial pulmonary disease, especially good at lung image diagnosis, lung difficulty, routine inspection and interventional treatment under bronchial mirrooscope Essence In 2009, he went to the National Institute of Cardiopulmonary, the Royal Institute of Britain, and published many theories in the SCIENTIFIC Reports, PLOS One, Allergy, Asthma Immunology Research and China Tuberculosis and Breathing Magazine.

Introduction to case review experts

Professor Su Mei

Chief physician and associate professor of the Department of Respiratory Department of Jiangsu Provincial People's Hospital

Learn

Member of the Sleep Professional Committee of the Chinese Medical Association

Member of the Jiangsu Medical Association Breathing Branch Sleeping Team

Member of the Chinese Sleep Research Association Sleep Disorders Committee

research direction

Mainly engaged in the diagnosis and treatment of respiratory diseases, and has a wealth of experience in diagnosis and treatment of respiratory tumors and sleep disorders. More than 20 articles are published, including 9 SCI articles, and participating in the National Natural Science Foundation of the National Natural Science Foundation.

references:

[1] .Recondo g, et al.Targeting meting dysregulation in car.cancer discov.2020 jul; 10 (7): 922-934.

[2] .noonan. Identifying the appropriated fireeria for defining metrivenocarcinoma through oncogene overlap analysis.j ThRELACNCOL. 2016; 11: 1293.

[3]. Non-small cell lung cancer molecular pathological test clinical practice guide (2021 version) [J]. Chinese pathology magazine, 2021, 50 (4): 323-332.

[4].Lai GGY, Lim TH, Lim J, et al. Clonal MET Amplification as a Determinant of Tyrosine Kinase Inhibitor Resistance in Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer. J Clin Oncol. 2019 Apr 10; 37 (11): 876-884.

[5] .moro-Sibilot D, et al. Crizotinib in C-MET-or Ros1-POSITIVE NSCLC: Results of the Acsé Phase II TRIAL. Ann Oncol.2019 DEC 1; 30 (12): 1985-1991

[6]. Camidge Dr, et al. Crizotinib in Patients with MET-AMPLIFIED NSCLC.

[7] .wolf j, et al. Capmatinib Inmetexon 14-Mutated Ormet-Amplify Non-Cell Lung Cancer.n English

[8] .le xn, et al. TEPOTINIB in Patients (PTS) with Advanced Non-Small Cell LUNG CANCER (NSCLC) withmetamplification (metamp). A, Nuttall B, et al. Et al. ET al. Mechaanisms of acquired resision to savolitinib, a selective met inhibitor in met-amplify gastric car. Jco Precis oncol. 2020; 4: PO.19.0038666.6.

[10].Gan HK, Millward M, Hua Y, et al. First-in-Human Phase I Study of the Selective MET Inhibitor, Savolitinib, in Patients with Advanced Solid Tumors: Safety, Pharmacokinetics, and Antitumor Activity. Clin Cancer Res . 2019; 25 (16): 4924-4932.

[11].Sequist LV, et al. Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: interim results from a multicentre, open-label, Phase 1B Study. Lancet Oncol. 2020 Mar; 21 (3): 373-386.

[12]. China Clinical Oncology Society (CSCO) non -small cell lung cancer diagnosis and treatment guide 2022.

[13] The China Clinical Oncology Society of Non -Cell Cancer Cancer Committee, the second -generation sequencing technology in the clinical application of Chinese experts in NSCLC (2020 version).

*This article is only used to provide scientific information to medical people, and does not represent the viewpoint of this platform

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